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Pulmonary delivery of antibiotics is an effective strategy in treating bacterial lung infection for cystic fibrosis patients, by achieving high local drug concentrations and reducing overall systemic exposure compared to systemic administration. However, the inherent anatomical lung defense mechanisms, formulation characteristics, and drug-device combination determine the treatment efficacy of the aerosol delivery approach. In this study, we prepared a new tobramycin (Tobi) dry powder aerosol using excipient enhanced growth (EEG) technology and evaluated the in vitro and in vivo aerosol performance. We further established a Pseudomonas aeruginosa-induced lung infection rat model using an in-house designed novel liquid aerosolizer device. Notably, novel liquid aerosolizer yields comparable lung infection profiles despite administering 3-times lower P. aeruginosa CFU per rat in comparison to the conventional intratracheal administration. Dry powder insufflator (e.g. Penn-Century DP-4) to administer small powder masses to experimental animals is no longer commercially available. To address this gap, we developed a novel rat air-jet dry powder insufflator (Rat AJ DPI) that can emit 68-70 % of the loaded mass for 2 mg and 5 mg of Tobi-EEG powder formulations, achieving a high rat lung deposition efficiency of 79 % and 86 %, respectively. Rat AJ DPI can achieve homogenous distribution of Tobi EEG powder formulations at both loaded mass (2 mg and 5 mg) over all five lung lobes in rats. We then demonstrated that Tobi EEG formulation delivered by Rat AJ DPI can significantly decrease CFU counts in both trachea and lung lobes at 2 mg (p < 0.05) and 5 mg (p < 0.001) loaded mass compared to the untreated P. aeruginosa-infected group. Tobi EEG powder formulation delivered by the novel Rat AJ DPI showed excellent efficiencies in substantially reducing the P. aeruginosa-induced lung infection in rats., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Michael Hindle, Worth Longest has patent EXCIPIENT ENHANCED GROWTH (EEG) OF NANOPARTICLE AEROSOLSTO ENABLE IMPROVED PULMONARY TARTETING AND RETENTION issued to Quench Medical. Michael Hindle, Worth Longest has patent DRY POWDER INHALER (DPI) DESIGN FOR PRODUCING AEROSOLS WITHHIGH FINE PARTICLE FRACTIONS issued to Quench Medical. Michael Hindle, Worth Longest, Dale Farkas has patent Dry powder inhalers and interfaces for improved aerosol delivery to children pending to Virginia Commonwealth University. Michael Hindle, Worth Longest, Dale Farkas has patent Devices, systems, and methods for dry powder therapies pending to Virginia Commonwealth University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Despite the growing prevalence of nanoplastics in drinking water distribution systems, the collective influence of nanoplastics and background nanoparticles on biofilm formation and microbial risks remains largely unexplored. Here, we demonstrate that nano-sized polystyrene modified with carboxyl groups (nPS) and background magnetite (nFe 3 O 4 ) nanoparticles at environmentally relevant concentrations can collectively stimulate biofilm formation and prompt antibiotic resistance. Combined exposure of nPS and nFe 3 O 4 by P. aeruginosa biofilm cells stimulated intracellular reactive oxidative species (ROS) production more significantly compared with individual exposure. The resultant upregulation of quorum sensing (QS) and c-di-GMP signaling pathways enhanced the biosynthesis of polysaccharides by 50 %- 66 % and increased biofilm biomass by 36 %- 40 % relative to unexposed control. Consistently, biofilm mechanical stability (measured as Young's modulus) increased by 7.2-9.1 folds, and chemical stress resistance (measured with chlorine disinfection) increased by 1.4-2.0 folds. For P. aeruginosa, the minimal inhibitory concentration of different antibiotics also increased by 1.1-2.5 folds after combined exposure. Moreover, at a microbial community-wide level, metagenomic analysis revealed that the combined exposure enhanced the multi-species biofilm's resistance to chlorine, enriched the opportunistic pathogenic bacteria, and promoted their virulence and antibiotic resistance. Overall, the enhanced formation of biofilms (that may harbor opportunistic pathogens) by nanoplastics and background nanoparticles is an overlooked phenomenon, which may jeopardize the microbial safety of drinking water distribution systems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Taniborbactam, a bicyclic boronate β-lactamase inhibitor with activity against Klebsiella pneumoniae carbapenemase (KPC), Verona integron-encoded metallo-β-lactamase (VIM), New Delhi metallo-β-lactamase (NDM), extended-spectrum beta-lactamases (ESBLs), OXA-48, and AmpC β-lactamases, is under clinical development in combination with cefepime. Susceptibility of 200 previously characterized carbapenem-resistant K. pneumoniae and 197 multidrug-resistant (MDR) Pseudomonas aeruginosa to cefepime-taniborbactam and comparators was determined by broth microdilution. For K. pneumoniae (192 KPC; 7 OXA-48-related), MIC 90 values of β-lactam components for cefepime-taniborbactam, ceftazidime-avibactam, and meropenem-vaborbactam were 2, 2, and 1 mg/L, respectively. For cefepime-taniborbactam, 100% and 99.5% of isolates of K. pneumoniae were inhibited at ≤16 mg/L and ≤8 mg/L, respectively, while 98.0% and 95.5% of isolates were susceptible to ceftazidime-avibactam and meropenem-vaborbactam, respectively. For P. aeruginosa , MIC 90 values of β-lactam components of cefepime-taniborbactam, ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam were 16, >8, >8, and >4 mg/L, respectively. Of 89 carbapenem-susceptible isolates, 100% were susceptible to ceftolozane-tazobactam, ceftazidime-avibactam, and cefepime-taniborbactam at ≤8 mg/L. Of 73 carbapenem-intermediate/resistant P. aeruginosa isolates without carbapenemases, 87.7% were susceptible to ceftolozane-tazobactam, 79.5% to ceftazidime-avibactam, and 95.9% and 83.6% to cefepime-taniborbactam at ≤16 mg/L and ≤8 mg/L, respectively. Cefepime-taniborbactam at ≤16 mg/L and ≤8 mg/L, respectively, was active against 73.3% and 46.7% of 15 VIM- and 60.0% and 35.0% of 20 KPC-producing P. aeruginosa isolates. Of all 108 carbapenem-intermediate/resistant P. aeruginosa isolates, cefepime-taniborbactam was active against 86.1% and 69.4% at ≤16 mg/L and ≤8 mg/L, respectively, compared to 59.3% for ceftolozane-tazobactam and 63.0% for ceftazidime-avibactam. Cefepime-taniborbactam had in vitro activity comparable to ceftazidime-avibactam and greater than meropenem-vaborbactam against carbapenem-resistant K. pneumoniae and carbapenem-intermediate/resistant MDR P. aeruginosa ., Competing Interests: Robert A. Bonomo reports grants from Venatorx, Entasis, Merck, Wockhardt, and Shionogi outside the submitted work. David A. Six, Greg Moeck, and Tsuyoshi Uehara are employees of Venatorx Pharmaceuticals, Inc.

The effectiveness of β-lactam antibiotics is increasingly threatened by resistant bacteria that harbor hydrolytic β-lactamase enzymes. Depending on the class of β-lactamase present, β-lactam hydrolysis can occur through one of two general molecular mechanisms. Metallo-β-lactamases (MBLs) require active site Zn 2+ ions, whereas serine-β-lactamases (SBLs) deploy a catalytic serine residue. The result in both cases is drug inactivation via the opening of the β-lactam warhead of the antibiotic. MBLs confer resistance to most β-lactams and are non-susceptible to SBL inhibitors, including recently approved diazabicyclooctanes, such as avibactam; consequently, these enzymes represent a growing threat to public health. Aspergillomarasmine A (AMA), a fungal natural product, can rescue the activity of the β-lactam antibiotic meropenem against MBL-expressing bacterial strains. However, the effectiveness of this β-lactam/β-lactamase inhibitor combination against bacteria producing multiple β-lactamases remains unknown. We systematically investigated the efficacy of AMA/meropenem combination therapy with and without avibactam against 10 Escherichia coli and 10 Klebsiella pneumoniae laboratory strains tandemly expressing single MBL and SBL enzymes. Cell-based assays demonstrated that laboratory strains producing NDM-1 and KPC-2 carbapenemases were resistant to the AMA/meropenem combination but became drug-susceptible upon adding avibactam. We also probed these combinations against 30 clinical isolates expressing multiple β-lactamases. E. coli , Enterobacter cloacae, and K. pneumoniae clinical isolates were more susceptible to AMA, avibactam, and meropenem than Pseudomonas aeruginosa and Acinetobacter baumannii isolates. Overall, the results demonstrate that a triple combination of AMA/avibactam/meropenem has potential for empirical treatment of infections caused by multiple β-lactamase-producing bacteria, especially Enterobacterales., Competing Interests: The authors declare no conflict of interest.

Background: The 2016 IDSA guideline recommends a treatment duration of at least 7 days for hospital-acquired (HAP)/ventilator-associated pneumonia (VAP). The limited literature has demonstrated higher rates of recurrence for non-glucose fermenting gram-negative bacilli with short course therapy, raising the concern of optimal treatment duration for these pathogens. Therefore, we aimed to compare the outcomes for patients receiving shorter therapy treatment (≤ 8 days) versus longer regimen (> 8 days) for the treatment of multidrug resistant (MDR) Pseudomonas pneumonia., Methods: A single-center, retrospective cohort study was conducted to evaluate adult patients receiving an antimicrobial regimen with activity against MDR Pseudomonas aeruginosa in respiratory culture between 2017 and 2020 for a minimum of 6 consecutive days. Exclusion criteria were inmates, those with polymicrobial pneumonia, community-acquired pneumonia, and infections requiring prolonged antibiotic therapy., Results: Of 427 patients with MDR P. aeruginosa respiratory isolates, 85 patients were included. Baseline characteristics were similar among groups with a median age of 65.5 years and median APACHE 2 score of 20. Roughly 75% had ventilator-associated pneumonia. Compared to those who received ≤ 8 days of therapy, no difference was seen for clinical success in patients treated for more than 8 days (80% vs. 65.5%, p = 0.16). The number of 30-day and 90-day in-hospital mortality, 30-days relapse, and other secondary outcomes did not significantly differ among the treatment groups., Conclusions: Prolonging treatment duration beyond 8 days did not improve patient outcomes for MDR P. aeruginosa HAP/VAP., (© 2024. The Author(s).)

A recent scientific investigation has shown promising results of selenium nanoparticles (SeNPs) for the anticancer and antimicrobial activities. This study aims to evaluate the effects of PVP SeNPs on bacterial strains, including Staphylococcus aureus (S. aureus), Bacillus cereus (B. cereus), Klebsiella pneumoniae (K. pneumoniae), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa). Also, its antitumor activity against the MRC-5 carcinoma cell line. SeNPs were prepared via gamma irradiation using PVP as a capping agent, and their size and morphological structure were determined using HRTEM. The size of the SeNPs ranged from 36 to 66.59 nm. UV-vis spectra confirmed the formation of SeNPs, while FTIR measurement confirmed a change in the PVP structure after adding selenium nanoparticles. The highest effect was reported on HepG2 by an IC50 with a value of 8.87 µg/ml, followed by HeLa, PC3, MCF-7, and Caco2 cell lines, respectively. Furthermore, ZOI reached 36.33 ± 3.05 mm. The best value of the minimum inhibitory concentration (MIC) was 0.313 µg/ml. Scanning electron microscope (SEM) imaging against bacteria showed deformations and distortions in their structures. Transmission electron (TEM) revealed ultrastructure changes in treated bacteria because of the free radicals that made cytotoxicity which confirmed by Electron spin resonance (ESR)., (© 2024. The Author(s).)

Efflux pumps and biofilm play significant roles in bacterial antibiotic resistance. This study investigates the potential of chlorogenic acid (CGA) and carnosol (CL), as phenolic and diterpene compounds, respectively, for their inhibitory effects on efflux pumps. Among the 12 multidrug-resistant (MDR) strains of Staphylococcus aureus and Pseudomonas aeruginosa isolated from nosocomial skin infections, eight strains were identified as extensively drug resistant (XDR) using the disc diffusion method. The presence of efflux pumps in MDR strains of S. aureus and P. aeruginosa was screened using carbonyl cyanide-m-chlorophenylhydrazone. Between the 12 MDR strains of S. aureus and P. aeruginosa , 80% (4 out of 5) of the S. aureus strains and 85.7% (6 out of 7) of the P. aeruginosa strains exhibited active efflux pumps associated with gentamicin resistance. The checkerboard assay results, in combination with gentamicin, demonstrated that CGA exhibited a reduction in the minimum inhibitory concentration (MIC) for XDR S. aureus strain. Similarly, CL showed a synergistic effect and reduced the MIC for both XDR strains of S. aureus and P. aeruginosa . Flow cytometry was used to examine efflux pump activity at sub-MIC concentrations of 1/8, 1/4, and 1/2 MIC in comparison to the control. In XDR S. aureus , CGA demonstrated 39%, 70%, and 19% inhibition, while CL exhibited 74%, 73.5%, and 62% suppression. In XDR P. aeruginosa , CL exhibited inhibition rates of 25%, 10%, and 15%. The inhibition of biofilm formation was assessed using the microtiter plate method, resulting in successful inhibition of biofilm formation. Finally, the MTT assay was conducted, and it confirmed minimal cytotoxicity. Given the significant reduction in efflux pump activity and biofilm formation observed with CGA and CL in this study, these compounds can be considered as potential inhibitors of efflux pumps and biofilm formation, offering potential strategies to overcome antimicrobial resistance., Importance: In summary, CGA and CL demonstrated promising potentiating antimicrobial effects against XDR strains of Staphylococcus aureus and Pseudomonas aeruginosa , suggesting their probably potential as candidates for addressing nosocomial pathogens. They exhibited significant suppression of efflux pump activity, indicating a possible successful inhibition of this mechanism. Moreover, all substances effectively inhibited biofilm formation, while showing minimal cytotoxicity. However, further advancement to clinical trials is needed to evaluate the feasibility of utilizing CGA and CL for reversing bacterial XDR efflux and determining their efficacy against biofilms. These trials will provide valuable insights into the practical applications of these compounds in combating drug-resistant infections., Competing Interests: The authors declare no conflict of interest.

Quorum sensing (QS) is a cell-cell signaling system that enables bacteria to coordinate population density-dependent changes in behavior. This chemical communication pathway is mediated by diffusible N -acyl L-homoserine lactone signals and cytoplasmic signal-responsive LuxR-type receptors in Gram-negative bacteria. As many common pathogenic bacteria use QS to regulate virulence, there is significant interest in disrupting QS as a potential therapeutic strategy. Prior studies have implicated the natural products salicylic acid, cinnamaldehyde, and other related benzaldehyde derivatives as inhibitors of QS in the opportunistic pathogen Pseudomonas aeruginosa, yet we lack an understanding of the mechanisms by which these compounds function. Herein, we evaluate the activity of a set of benzaldehyde derivatives using heterologous reporters of the P. aeruginosa LasR and RhlR QS signal receptors. We find that most tested benzaldehyde derivatives can antagonize LasR or RhlR reporter activation at micromolar concentrations, although certain molecules also cause mild growth defects and nonspecific reporter antagonism. Notably, several compounds showed promising RhlR or LasR-specific inhibitory activities over a range of concentrations below that causing toxicity. ortho -Vanillin, a previously untested compound, was the most promising within this set. Competition experiments against the native ligands for LasR and RhlR revealed that ortho -vanillin can interact competitively with RhlR but not with LasR. Overall, these studies expand our understanding of benzaldehyde activities in the LasR and RhlR receptors and reveal potentially promising effects of ortho -vanillin as a small molecule QS modulator against RhlR., Importance: Quorum sensing (QS) regulates many aspects of bacterial pathogenesis and has attracted much interest as a target for anti-virulence therapies over the past 30 years, for example, antagonists of the LasR and RhlR QS receptors in Pseudomonas aeruginosa . Potent and selective QS inhibitors remain relatively scarce. However, natural products have provided a bounty of chemical scaffolds with anti-QS activities, but their molecular mechanisms are poorly characterized. The current study serves to fill this void by examining the activity of an important and wide-spread class of natural product QS modulators, benzaldehydes, and related derivatives, in LasR and RhlR. We demonstrate that ortho -vanillin can act as a competitive inhibitor of RhlR, a receptor that has emerged and may supplant LasR in certain settings as a target for P. aeruginosa QS control. The results and insights provided herein will advance the design of chemical tools to study QS with improved activities and selectivities., Competing Interests: The authors declare no conflict of interest.

Background: β-lactam antibiotics, which inhibit penicillin-binding protein 3 (PBP3) that is required for cell division, play a key role in treating P. aeruginosa infections. Some sequence variations in PBP3 have been associated with β-lactam resistance but the effects of variations on antibiotic susceptibility and on cell division have not been quantified. Antibiotic efflux can also reduce susceptibility., Objectives: To quantify the effects of PBP3 variations on β-lactam susceptibility and cell morphology in P. aeruginosa., Methods: Nineteen PBP3 variants were expressed from a plasmid in the reference strain P. aeruginosa PAO1 and genome engineering was used to construct five mutants expressing PBP3 variants from the chromosome. The effects of the variations on β-lactam minimum inhibitory concentration (MIC) and cell morphology were measured., Results: Some PBP3 variations reduced susceptibility to a variety of β-lactam antibiotics including meropenem, ceftazidime, cefepime and ticarcillin with different variations affecting different antibiotics. None of the tested variations reduced susceptibility to imipenem or piperacillin. Antibiotic susceptibility was further reduced when PBP3 variants were expressed in mutant bacteria overexpressing the MexAB-OprM efflux pump, with some variations conferring clinical levels of resistance. Some PBP3 variations, and sub-MIC levels of β-lactams, reduced bacterial growth rates and inhibited cell division, causing elongated cells., Conclusions: PBP3 variations in P. aeruginosa can increase the MIC of multiple β-lactam antibiotics, although not imipenem or piperacillin. PBP3 variations, or the presence of sub-lethal levels of β-lactams, result in elongated cells indicating that variations reduce the activity of PBP3 and may reduce bacterial fitness., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: Bacterial RNA polymerase (RNAP) is a promising target for antimicrobial chemotherapy due to its indispensable role in bacterial growth and survival. Among its components, only the rpoB gene encoding the β-subunit is known for its association with rifampicin resistance. We recently identified a variant of the RNAP α-subunit (RpoA) in Pseudomonas aeruginosa, conferring heightened bacterial susceptibility to antimicrobials. This susceptibility was attributed to the specific down-regulation of the MexEF-OprN efflux pump., Objectives: We asked how to distinguish antimicrobial-susceptible variant strains from clinical isolates., Methods: In this study, we identified various P. aeruginosa RpoA variants from clinical sources. Using the sequence alignment of different bacterial RpoA species, we computed the positional conservation of substitutions in RpoA variants using Shannon Entropy., Results: Our findings revealed that selective RpoA variant strains exhibited distinct profiles of antimicrobial susceptibility. Notably, RpoA variant strains, containing single-substitutions in the C-terminal domain (α-CTD) but not the N-terminal domain (α-NTD), showed attenuated MexEF-OprN expression and increased susceptibility to MexEF-OprN-specific antibiotics. Furthermore, we observed a close correlation between the susceptibility of these α-CTD RpoA variant strains to antibiotics and the conservation degrees of positional substitutions., Conclusions: Our findings demonstrate the prevalence of antimicrobial-susceptible RpoA variant strains among P. aeruginosa clinical isolates. The identified positional conservation pattern in our study facilitates the rapid classification of RpoA variant strains with distinct drug resistances. Given the high conservation of RNAP across bacterial species, our findings open a new therapeutic perspective for precisely and efficiently combating pathogenic RpoA variant strains with specific antimicrobials., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: The measurement of VOCs release in the headspace of a bacterial culture represents a new approach to rapidly assess antimicrobial susceptibility. Herein, we evaluated the diagnostic performance of the VITEK® REVEAL™ system directly from a collection of Gram-negative positive blood cultures., Materials and Methods: One hundred and twenty-eight positive blood cultures were included in the analysis (Enterobacterales, n = 95; Pseudomonas aeruginosa, n = 21; Acinetobacter baumannii complex, n = 12). Samples were processed using VITEK® REVEAL™ according to the manufacturer's recommendations, and MICs of 22 antimicrobials were compared with those obtained using reference methods. Categorical agreement (CA), essential agreement (EA) and categorical errors were calculated., Results: Overall, 2220 strain/antibiotic pair combinations were analysed. Of these, most were classified as resistant by reference antimicrobial susceptibility testing (1091/2220; 48.7%). The overall CA and EA were 97.6% and 97.7%, respectively. CA ranged from 97.5% in Enterobacterales to 97.9% in both P. aeruginosa and A. baumannii complex. The overall number of categorical discrepancies were: 18 very major errors (1.6%), 13 major errors (1.2%) and 22 minor errors (2.4%). EA ranged from 95.2% in P. aeruginosa to 98.1% in Enterobacterales. Screening test for ESBL phenotype was positive, indeterminate and negative in 13.7%, 32.6% and 27.4% of Enterobacterales isolates tested by both VITEK® REVEAL™ and the reference method, showing 100% CA., Conclusions: VITEK® REVEAL™ represents a reliable tool to obtain antimicrobial susceptibility results of the main Gram-negative species directly from positive blood cultures with time to results of less than 8 h., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Carbapenem-resistant Pseudomonas aeruginosa (CRPa) infection is extremely challenging to manage. Cefepime-zidebactam is a novel combination that can be considered for salvage therapy when no other antimicrobials are susceptible. A 15-y-old boy presented with 56% thermal burns, followed by skin and soft tissue infection, secondary bacteraemia, complicated parapneumonic effusion and endophthalmitis due to CRPa, which was not susceptible to any of the routinely available antibiotics. He was treated with cefepime-zidebactam for 45 d, with which he recovered., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

PEGylated branched polyethylenimine (PEG-BPEI) has antibacterial and antibiofilm properties. Exposure to PEG-BPEI through serial passage leads to resistant P. aeruginosa strains. The minimum inhibitory concentration (MIC) of 600 Da BPEI and PEGylated 600 Da BPEI (PEG-BPEI) in the wild-type PAO1 strain is 16 μg/ml while, after 15 serial passages, the MIC increased to 1024 μg/mL. An additional 15 rounds of serial passage in the absence of BPEI or PEG-BPEI did not change the 1024 μg/mL MIC. Gentamicin, Neomycin, and Tobramycin, cationic antibiotics that inhibit protein synthesis, have a 16-32 fold reduction of MIC values in PEG350-BPEI resistant strains, suggesting increased permeation. The influx of these antibiotics occurs using a self-mediated uptake mechanism, suggesting changes to the outer membrane Data show that resistance causes changes in genes related to outer membrane lipopolysaccharide (LPS) assembly. Mutations were noted in the gene coding for the polymerase Wzy that participates in the assembly of the O-antigen region. Other mutations were noted with wbpE and wbpI of the Wbp pathway responsible for the enzymatic synthesis of ManNAc(3NAc)A in the LPS of P. aeruginosa. These changes suggest that an altered gene product could lead to PEG-BPEI resistance. Nevertheless, the increased susceptibility to aminoglycosides could prevent the emergence of PEG-BPEI resistant bacterial populations., (© 2024 Wiley-VCH GmbH.)

Our laboratory recently developed a new class of high surface area, honeycomb Nanoclay Microsphere Framework absorbents (NMFs) that prompt rapid hemostasis. In the present work, we propose a novel approach to develop antibacterial Topical Hemostatic Agents (THAs) by anchoring silver nanoparticles (AgNPs) onto NMFs. This combination was obtained by a chemical co-reduction approach, followed by freeze-processing, and was shown to ensure stability and on-site delivery of AgNPs, without altering the hemostatic properties of NMFs. Silver-loaded NMFs showed no change in their unique architecture and led to a 55% increase in clot strength, compared to standard control plasma or commercially available THA, and a significant decrease in mean fibrin fiber diameter. Silver nanoparticles were successfully released when solubilized and prevented the growth of both Pseudomonas aeruginosa and Staphylococcus aureus at concentrations of 22 and 30 ppm of silver released, respectively. Overall, cell mortality was between 9.1 ± 5.1% and 6.3 ± 3.2%, depending on AgNP concentration, confirming a low cytotoxicity. Silver-loaded nanoclay microsphere frameworks appear to constitute promising candidates as topical hemostatic agents for secondary management of hemostasis when infection control is needed., (© 2024 The Author(s). Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals LLC.)

Marine microorganisms offer a promising avenue for the eco-friendly synthesis of nanoparticles due to their unique biochemical capabilities and adaptability to various environments. This study focuses on exploring the potential of a marine bacterial species, Stenotrophomonas rhizophila BGNAK1, for the synthesis of biocompatible copper nanoparticles and their application for hindering biofilms formed by monomicrobial species. The study begins with the isolation of the novel marine S. rhizophila species from marine soil samples collected from the West coast region of Kerala, India. The isolated strain is identified through 16S rRNA gene sequencing and confirmed to be S. rhizophila species. Biosynthesis of copper nanoparticles using S. rhizophila results in the formation of nanoparticles with size of range 10-50 nm. The nanoparticles exhibit a face-centered cubic crystal structure of copper, as confirmed by X-Ray Diffraction analysis. Furthermore, the synthesized nanoparticles display significant antimicrobial activity against various pathogenic bacteria and yeast. The highest inhibitory activity was against Staphylococcus aureus with a zone of 27 ± 1.00 mm and the least activity was against Pseudomonas aeruginosa with a zone of 22 ± 0.50 mm. The zone of inhibition against Candida albicans was 16 ± 0.60 mm. The antibiofilm activity against biofilm-forming clinical pathogens was evidenced by the antibiofilm assay and SEM images. Additionally, the copper nanoparticles exhibit antioxidant activity, as evidenced by their scavenging ability against DPPH, hydroxyl, nitric oxide, and superoxide radicals, as well as their reducing power in the FRAP assay. The study highlights the potential of the marine bacterium S. rhizophila BGNAK1 for the eco-friendly biosynthesis of copper nanoparticles with diverse applications. Synthesized nanoparticles exhibit promising antibiofilm, antimicrobial, and antioxidant properties, suggesting their potential utility in various fields such as medicine, wastewater treatment, and environmental remediation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Bacterial biofilms pose a significant threat to healthcare due to their recalcitrance to antibiotics and disinfectants. This study explores the anti-biofilm potential of Bacillus licheniformis cell-free culture supernatant (CFS) and its derived silver nanoparticles (bSNPs) against Staphylococcus aureus and Pseudomonas aeruginosa. The CFS exhibited potent anti-biofilm activity against both bacterial species, even at low concentrations, while devoid of significant bactericidal effects, mitigating resistance risks. Characterization studies revealed the non-proteinaceous nature and thermal stability of the CFS's anti-biofilm agent, suggesting a robust and heat-resistant structure. Green synthesis of bSNPs from CFS resulted in nanoparticles with significant anti-biofilm properties, particularly against P. aeruginosa, indicating differences in susceptibility between the bacterial species. Epifluorescence microscopy confirmed bSNPs' ability to inhibit and partially disrupt biofilm formation without inducing cellular lysis. The study highlights the potential of B. licheniformis CFS and bSNPs as promising biofilm control agents, offering insights into their mechanisms of action and broad-spectrum efficacy. Further research elucidating the underlying molecular mechanisms and identifying specific bioactive compounds is warranted for the translation of these findings into clinically relevant applications for combating biofilm-associated infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Pseudomonas aeruginosa infections have become a serious threat to public health due to the increasing emergence of extensively antibiotic-resistant strains and high mortality rates. Therefore, the search for new therapeutic alternatives has become crucial. In this study, the antivirulence and antibacterial activity of methyl gallate was evaluated against six clinical isolates of extensively antibiotic-resistant P. aeruginosa. Methyl gallate exhibited minimal inhibitory concentrations of 256-384 μg/mL; moreover, the use of subinhibitory concentrations of the compound inhibited biofilm formation, swimming, swarming, proteolytic activity, and pyocyanin production. Methyl gallate plus antipseudomonal antibiotics showed a synergistic effect by reduced the MICs of ceftazidime, gentamicin and meropenem. Furthermore, the potential therapeutic effect of methyl gallate was demonstrated in an infection model. This study evidenced the antivirulence and antimicrobial activity of methyl gallate as a therapeutic alternative against P. aeruginosa., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: KPC-2-producing Pseudomonas aeruginosa high-risk sequence type (ST) 463 is increasingly prevalent in China and poses severe threats to public health. In this study, we aimed to investigate within-host adaptive evolution of this clone during therapy., Methods: Using nine serial respiratory isolates from a post-lung transplantation patient undergoing multiple antibiotic treatments, we conducted genomic, transcriptomic and phenotypic analyses to uncover the adaptive mechanisms of a KPC-2-producing ST463 P. aeruginosa strain., Results: The early-course isolates exhibited low-level resistance to ceftazidime/avibactam (CZA), facilitated by the bla KPC-2 gene's presence on both chromosome and plasmid, and its overexpression. Comparative genomic analysis revealed that chromosomal integration of bla KPC-2 resulted from intracellular replicative transposition of the plasmid-derived IS26-bla KPC-2 -IS26 composite transposon. As the infection progressed, selective pressures, predominantly from antibiotic interventions and host immune response, led to significant genomic and phenotypic changes. The late-course isolates developed a Δ242-GT-243 deletion in plasmid-encoded bla KPC-2 (bla KPC-14 ) after sustained CZA exposure, conferring high-level CZA resistance. Increased expression of pili and extracellular polysaccharides boosted biofilm formation. A D143N mutation in the global regulator vfr rendered the strain aflagellate by abrogating the ability of fleQ to positively regulate flagellar gene expression. The enhancement of antibiotic resistance and immune evasion collaboratively facilitated the prolonged survival of ST463 P. aeruginosa within the host., Conclusions: Our findings highlight the remarkable capacity of ST463 P. aeruginosa in adapting to the dynamic host pressures, supporting its persistence and dissemination in healthcare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: In this study, we evaluated the effectiveness of antimicrobial blue light (aBL; 410 nm wavelength) against β-lactamase-carrying bacteria and the effect of aBL on the activity of β-lactamases., Methods: Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae strains carrying β-lactamases as well as a purified β-lactamase enzymes were studied. β-lactamase activity was assessed using a chromogenic cephalosporin hydrolysis assay. Additionally, we evaluated the role of porphyrins in the photoreaction, as well as protein degradation by sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Finally, we investigated the bactericidal effect of combined aBL-ceftazidime exposure against a metallo-β-lactamase expressing P. aeruginosa strain., Results: Our study demonstrated that aBL effectively killed β-lactamase-producing bacteria and reduced β-lactamase activity. After an aBL exposure of 1.52 J/cm 2 , a 50% reduction in enzymatic activity was observed in P. aeruginosa. Additionally, we found a 40% decrease in the photoreaction activity of porphyrins following an aBL exposure of 64.8 J/cm 2 . We also revealed that aBL reduced β-lactamase activity via protein degradation (after 136.4 J/cm 2 ). Additionally, aBL markedly improved the bactericidal effect of ceftazidime (by >4-log 10 ) in the metallo-β-lactamase P. aeruginosa strain., Conclusion: Our results provide evidence that aBL compromises bacterial β-lactamase activity, offering a potential approach to overcome β-lactam resistance in bacteria., (© 2024 Wiley Periodicals LLC.)

Polyethylene terephthalate (PET) and polylactic acid (PLA) are among the polymers used in the food industry. In this study, crude extracts of Dunaliella salina were used to treat the surface of 3D printed materials studied, aiming to provide them with an anti-adhesive property against Pseudomonas aeruginosa . The hydrophobicity of treated and untreated surfaces was characterized using the contact angle method. Furthermore, the adhesive behavior of P. aeruginosa toward the substrata surfaces was also studied theoretically and experimentally. The results showed that the untreated PLA was hydrophobic, while the untreated PET was hydrophilic. It was also found that the treated materials became hydrophilic and electron-donating. The total energy of adhesion revealed that P. aeruginosa adhesion was theoretically favorable on untreated materials, while it was unfavorable on treated ones. Moreover, the experimental data proved that the adhesion to untreated substrata was obtained, while there was complete inhibition of adhesion to treated surfaces.

Objectives: Staphylococcus aureus and Pseudomonas aeruginosa co-infections in patients with cystic fibrosis (CF) are associated with disease severity. Their treatment is complicated by biofilm formation in the sticky mucus obstructing the airways. We investigated the activity of phages-antibiotics combinations using a dual species biofilm (P. aeruginosa/S. aureus) formed in artificial sputum medium., Methods: Biofilmswere incubated with broad-spectrum antibiotics (meropenem, ceftazidime, ciprofloxacin, tobramycin) combined with a cocktail of two (bacterio)phages (PSP3 and ISP) proven active via spot tests and double agar on P. aeruginosa PAO1 and S. aureus ATCC 25923., Results: At the highest tested concentrations (100 x MIC), antibiotics alone caused a 20-50% reduction in biomass and reduced S. aureus and P. aeruginosa CFU of 2.3 to 2.8 and 2.1 to 3.6 log 10 , respectively. Phages alone reduced biofilm biomass by 23% and reduced P. aeruginosa CFU of 2.1 log 10 , but did not affect S. aureus viability. Phages enhanced antibiotic effects on biomass and exhibited additive effects with antibiotics against P. aeruginosa, but not against S. aureus. Following inhibition of bacterial respiration by phages in planktonic cultures rationalised these observations by demonstrating that PSP3 was effective at multiplicities of infection (MOI) as low as 10 -4 plaque forming units (PFU)/CFU on P. aeruginosa, but ISP, at higher MOI (> 0.1) against S. aureus., Conclusion: Pre-screening inhibition of bacterial respiration by phages may assist in selecting those showing activity at sufficiently low titers to showcase anti-biofilm activity in this complex but clinically-relevant in vitro model of biofilm., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Objectives: Colistin sulphate for injection (CSI) became clinically available in China in July 2019. To date, there is no published data regarding its usage in children. Our research group has been following data on the efficacy and safety of CSI in Chinese paediatric patients with carbapenem-resistant organism infections. The purpose of this short communication is to provide a brief overview of the findings to date., Methods: We reviewed the electronic medical records of paediatric patients (aged 9-17 y) who were administered CSI during their hospital stay at Tongji Hospital in Wuhan, China, between June 2021 and November 2023. Drug efficacy was evaluated based on clinical and microbiological outcomes, while drug safety was assessed using surveillance markers that reflect adverse reactions., Results: A total of 20 patients met the inclusion criteria. The predominant pathogens were Klebsiella pneumoniae (8 strains), followed by Acinetobacter baumannii (5 strains) and Pseudomonas aeruginosa (2 strains). The clinical response rate of CSI was 85%, with a bacterial clearance rate of 79%. None of the patients experienced colistin-related nephrotoxicity or neurotoxicity during the treatment., Conclusions: In this real-world setting, CSI demonstrated a high level of clinical response and was well tolerated for the treatment of carbapenem-resistant organism infections in Chinese children., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Carbapenem resistant Pseudomonas aeruginosa (CR-PA) is escalating worldwide and leaves clinicians few therapeutic options in recent years, β-lactam/β-lactamase inhibitor combinations (ceftolozane-tazobactam, ceftazidime-avibactam) and a new siderophore cephalosporin (cefiderocol) have been approved for the treatment of P. aeruginosa infection and have shown potent activity against isolates defined as carbapenem resistant. The aim of this study was to determine the phenotypic profile of these agents against CR-PA in the emerging setting of carbapenemases., Methods: CR-PA clinical isolates were collected from three teaching hospitals in different geographical regions between January 2017-December 2021. All isolates were subjected to phenotypic carbapenemase testing using modified carbapenem inactivation method. MICs were determined by reference broth microdilution and evaluated according to EUCAST standards, while genotypic profiling was determined using PCR methods., Results: 244 CR-PA sourced most frequently from the respiratory tract (32.2%), blood (20.4%) and urine (17.5%) were evaluated. Of all isolates, 32 (13.1%) were phenotypically and 38 (15.6%) were genotypically defined as carbapenemase-positive. The most common carbapenemase was GES (63.1%), followed by VIM (15.8%). The MIC 50/90 (S%) of ceftazidime/avibactam, ceftolozane/tazobactam and cefiderocol in all CR-PA isolates were 4 and 32 (80%), 1 and > 64 (69%) and 0.25 and 1 mg/L (96%), respectively. Cefiderocol was also the most active agent in carbapenemase-positive isolates (90%)., Conslusion: While ceftolozane/tazobactam and ceftazidime/avibactam remained highly active against CR-PA devoid of carbapenemases, cefiderocol provided potent in vitro activity irrespective of carbapenemase production. When considering the potential clinical utility of newer agents against CR-PA, regional variations in carbapenemase prevalence must be considered., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Pseudomonas aeruginosa is a leading cause of nosocomial Gram-negative bacteraemia. Water systems are a well-documented source of P. aeruginosa and established biofilms are difficult to remove., Aim: To evaluate the efficacy of regular flushing, peracetic acid disinfection, in-tap thermal disinfection, and in-line thermal disinfection to eradicate P. aeruginosa biofilm in a colonized tap model., Methods: A simulated tap system was constructed and inoculated with a reference and an environmental strain of P. aeruginosa to form biofilm. Water samples were collected from the taps and P. aeruginosa levels enumerated following disinfection methods. To simulate regular flushing, taps were flushed for 5 min, five times per day with water tested daily. Peracetic acid (4000 ppm) was manually injected into the system and flushed through the system with a pump. Thermal flushing at 60 °C was performed in-line and with an in-tap bypass valve. Tests were conducted with cross-linked polyethylene (PEX) piping and repeated with copper piping., Findings: Regular flushing and peracetic acid applied with a pump did not reduce P. aeruginosa levels. A limited reduction was observed when manually injecting peracetic acid. In-tap thermal flushing eradicated P. aeruginosa in copper piping but not PEX. In-line thermal flushing was the most effective at reducing P. aeruginosa levels; however, it did not eradicate the biofilm., Conclusion: In-line thermal flushing was the most effective method to remove P. aeruginosa biofilm. Results vary significantly with the strain of bacteria and the composition of the plumbing. Several methods used in combination may be necessary to remove established biofilm., (Copyright © 2024 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Burn injuries worldwide pose significant health risks due to frequent microbial infections, which worsen complications and increase mortality rates. The conventional antimicrobial formulations are available in the form of ointments and creams. These formulations are very greasy and stick to the clothes. The applications of these formulations by finger or applicator produce pain in the affected area and incur the possibility of microbial infection. To overcome these hurdles, authors developed a novel non-propellent foam (NPF) based formulation containing chlorhexidine for effective topical delivery. Initially, NPF containing Labrasol® (26.7%), sodium lauryl sulfate (1.2%), hydroxy propyl methyl cellulose (0.56%), butylated hydroxytoluene (0.1%), ethanol (1%), and distilled water was prepared and assessed for its consistency, and ability to form foam. The NPF was statistically optimized using the Box-Behnken design to determine the effect of polymer and surfactants on the critical foam properties. The optimized formulation showed a collapse time of 45 s with a unique nature of collapsing upon slight touch which is highly beneficial for burn patients with microbial infection. The diffusion study showed that more than 90% of the drug was released within 6 h. The skin permeation study showed that 23% of the total drug permeated through the skin after 6 h with 7.64 µg/cm 2 /h permeation flux. The developed formulation showed good antibacterial activity. The minimum inhibitory concentration of prepared NPF was found to be 2.5 µg/mL, 2.5 µg/mL, and 5.0 µg/mL against E. coli (MTCC-1687), P. aeruginosa (MTCC-1688), and S aureus (MTCC-737) respectively. The developed NPF formulation showed quick collapse time, excellent spreadability, good anti-bacterial activity, and a non-sticky nature representing a promising avenue for burn wound treatment without using any applicator., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Objectives: The proliferation of metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa represents a significant public health threat. P. aeruginosa undergoes significant phenotypic changes that drastically impair antibiotic efficacy. The objectives of this study were (1) to quantify the time-course of killing of VIM-2-producing P. aeruginosa in response to aztreonam-based therapies (including avibactam for coverage of AmpC), and (2) to document the capacity of P. aeruginosa to undergo morphological transformations that facilitate persistence., Methods: A well-characterised, clinical VIM-2-producing P. aeruginosa was studied in the hollow fibre infection model (HFIM) over 9 days (7 days of active antibiotic therapy, 2 days of treatment withdrawal) at a 10 7.5 CFU/mL starting inoculum. HFIM treatment arms included: growth control, aztreonam, ceftazidime/avibactam, aztreonam/ceftazidime/avibactam, polymyxin B, and aztreonam/ceftazidime/avibactam/polymyxin B. In addition, real-time imaging studies were conducted under static conditions to determine the time course of the reversion of persister cells., Results: There was a pronounced discrepancy between OD 620 and bacterial counts obtained from plating methods (hereafter referred to as 'OD-count discrepancy'). For aztreonam monotherapy, observed counts were 0 CFU/mL by 120 h. Despite this, there was a significant OD-count discrepancy compared with the pre-treatment 0 h. Between therapy withdrawal at 168 h and 216 h, all arms with suppressed counts had regrown to the system-carrying capacity. Real-time imaging of the P. aeruginosa filaments after drug removal showed rapid reversion from a long, filamentous phenotype to many individual rods within 2 h., Conclusion: Managing MBL-producing P. aeruginosa requires a multifaceted approach, focused on maximising killing and minimising proliferation of resistant and persistent subpopulations, which will involve eliminating drug-induced phenotypic transformers., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Di-branched and tetra-branched versions of a previously reported analogue of the lipopeptide battacin were successfully synthesised using thiol-maleimide click and 1, 2, 3-triazole click chemistry. Antimicrobial studies against drug resistant clinical isolates of Escherichia coli (ESBL E. coli Ctx-M14), Pseudomonas aeruginosa (P. aeruginosa Q502), and Methicillin resistant Staphylococcus aureus (MRSA ATCC 33593), as well as clinically isolated Acinetobacter baumannii (A. baumannii ATCC 19606), and P. aeruginosa (ATCC 27853), revealed that the dendrimeric peptides have antimicrobial activity in the low micromolar range (0.5 -- 4 μM) which was 10 times more potent than the monomer peptides. Under high salt concentrations (150 mM NaCl, 2 mM MgCl 2 , and 2.5 mM CaCl 2 ) the di-branched lipopeptides retained their antimicrobial activity while the monomer peptides were not active (>100 μM). The di-branched triazole click lipopeptide, Peptide 12, was membrane lytic, showed faster killing kinetics, and exhibited antibiofilm activity against A. baumannii and MRSA and eradicated > 85 % preformed biofilms at low micromolar concentrations. The di-branched analogues were > 30-fold potent than the monomers against Candida albicans. Peptide 12 was not haemolytic (HC10 = 932.12 μM) and showed up to 40-fold higher selectivity against bacteria and fungi than the monomer peptide. Peptide 12 exhibited strong proteolytic stability (>80 % not degraded) in rat serum over 24 h whereas > 95 % of the thiol-maleimide analogue (Peptide 10) was degraded. The tetra-branched peptides showed comparable antibacterial potency to the di-branched analogues. These findings indicate that dual branching using triazole click chemistry is a promising strategy to improve the antimicrobial activity and proteolytic stability of battacin based lipopeptides. The information gathered can be used to build effective antimicrobial dendrimeric peptides as new peptide antibiotics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Microplastics in the aquatic environment are susceptible to colonization by surrounding microorganisms, which form biofilms over the microplastic's surface. These biofilm-laden microplastics can then interact with a diverse array of contaminants. In the present study, biofilms were grown on microplastics in a laboratory setting using Pseudomonas aeruginosa as a model biofilm-forming bacterium for periods of 5 to 15 days. The sorption of three organic compounds representing different levels of hydrophobicity, namely methylene blue (MB), phenanthrol, and phenanthrene, was used to evaluate the effect of biofilm biomass on the adsorption of organic contaminants to microplastics. The sorption of MB and phenanthrol was found to increase with biofouling time, indicating affinity between these contaminants and the biofilm biomass on the particle. However, the presence of a biofilm did not influence the sorption of phenanthrene on the microplastics. These results suggest that the hydrophobicity of organic contaminants plays a major role in how biofouling of microplastics will influence contaminant sorption by microplastics. For some contaminants, biofilm can enhance the role of microplastics as contaminant vectors. These findings emphasize the need to understand the biomass load on environmental microplastics and the contaminants that associate with it for an accurate representation of the risk associated with microplastics in the environment. Environ Toxicol Chem 2024;43:1973-1981. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC., (© 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.)

Introduction: Pseudomonas aeruginosa is a Gram-negative water-borne opportunistic pathogen. Reservoirs of bacteria can infect vulnerable populations. Mitigation of this risk in health care includes regular microbiology monitoring and chemical/thermal disinfection of outlets. Where contamination is persistent, point-of-use filters/antimicrobial showers may be used to reduce the bioburden. This study tested the efficacy of a silver nanoparticle (Ag + )-impregnated antimicrobial showerhead against P. aeruginosa under simulated conditions., Methods: Test (excised from Ag + -impregnated showerhead) and control (stainless steel) coupons (∼1 cm 2 ; N=108) were inoculated with 10 μL [∼10 3  colony-forming units (CFU)] P. aeruginosa (NCTC 10662 and wild-types) and overlaid with coverslips. Coupons were incubated at ambient temperature (∼40% relative humidity) for 0 min, 30 min, 2 h, 4 h and 24 h. Coupons and coverslips were transferred to neutralizer solution, followed by bead washing for bacterial recovery and enumeration., Results: Contamination ranged from ∼2.90 log 10  CFU (±0.14 log 10 ; type strain) to ∼3.02 log 10  CFU (±0.16 log 10 ; wild-types). No significant reductions in the P. aeruginosa bioburden were observed for any of the three strains (P>0.05). Analogous bacterial decline was noted between the test and control coupons (falling to below the detection limit) between 4 and 24 h, possibly due to desiccation., Summary: Whilst being an economically and environmentally friendly option, antimicrobial showers may not be appropriate to reduce the bioburden in healthcare waters. Previous research has demonstrated the bactericidal effects of Ag + ; however, this was not established in the present study. Although the concentration of silver in the test materials was unknown, these findings suggest that antimicrobial showerheads may require higher concentrations of Ag + to display antimicrobial activity. Further testing is required to determine efficacy against biofilms., (Copyright © 2024 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Antibiotic resistant is the major concern in public health to control the infectious diseases. MRSA (Methicillin-resistant Staphylococcus aureus) is a significant concern in healthcare settings due to its resistance to many antibiotics, including methicillin and other beta-lactams. MRSA infection difficult to treat and increases the risk of complications. Here, we have tested a series of highly condensed heterocyclic derivatives of pyrrolo[1,2-a][1,4]benzodiazepines. Compounds were tested against both, Gram-positive bacteria, Staphylococcus aureus and S. epidermidis, and Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, to assess the antimicrobial efficacy. Compared to Gram-negative bacteria, compounds showed much stronger antibacterial activity against Gram-positive bacteria. SM-5 [Ethyl2-(7-(4-chlorophenyl)-4-methoxy-6,7,8,13-tetrahydro-5H-benzo[e]benzo[5,6][1,4]diazepino[2,1-a]isoindol-15-yl)acetate] derivative was selected as best on the basis of higher therapeutic index among the tested compounds, showed MIC value of 7.81 µg. ml -1 against Staphylococcus strains. Molecular docking analysis between cell wall biosynthesis protein of S. aureus and SM-5 revealed that PBP2a showed the highest binding energy (-8.3 Kcal mol -1 ), followed by beta-lactam-inducible PBP4 (-7.7 Kcal mol -1 ), and lipoteichoic acid synthase (-7.5 Kcal mol -1 ) which is comparably higher than methicillin. Ground state energy calculations by DFT analysis revealed that compound SM-5 and SM-6, almost have equal electronegativity 0.11018 au which also satisfy the quality of the compound reactivity. Analysis of their biofilm inhibition in vitro and in silico toxicity analysis demonstrated their substantial potential to be a kind of future lead antibiotic., (© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Purpose: This study compared the anti-pseudomonal effects between nephrite-impregnated contact lenses (CLs) and conventional and cosmetic CLs., Methods: After inoculation with Pseudomonas aeruginosa (P.aeruginosa) , we counted the number of bacteria on the CL surface and observed each surface using atomic force microscopy (AFM) and scanning electron microscopy (SEM). To estimate potential harm of nephrite-impregnated CLs, we conducted a safety test using a rabbit model, treated with all CL types., Results: Both conventional and cosmetic CLs ( n  = 258 ± 2.9 × 10 4 , 368 ± 2.2 × 10 4 ) showed significantly decreased number of attached bacteria when compared with those without nephrite impregnation ( n  = 134 ± 0.8 × 10 4 , 238 ± 2.5 × 10 4 , p  < 0.0001, respectively). AFM and SEM revealed that P. aeruginosa was less attached to the nephrite-impregnated CLs than to the conventional and cosmetic CLs, although those with nephrite impregnation had rougher surface. In the safety test, there were no significant differences in the findings between four groups, and the clarity and stability of all corneas were preserved., Conclusions: Nephrite may be used as a next-generation substance to reduce infectious keratitis caused by P. aeruginosa when added to CLs.

Antimicrobial resistance is emerging as the new healthcare crisis necessitating the development of newer classes of drugs using non-traditional approaches. Pseudomonas aeruginosa, one of the most common pathogens involved in nosocomial infections, is extremely difficult to treat even with the last resort frontline drug, the carbapenems. As the pathogen has the ability to acquire resistance to new small-molecule antibiotics, being deployed, a novel biological approach has been tried using antibody fragments in combination with carbapenems and β-lactams as adjunct therapy for an enduring solution to the problem. In this study, we developed a camelid antibody fragment (VHH) library against P. aeruginosa and isolated a highly potent hit, PsC23. Mass spectrometry identified the target to be a component of the C4-dicarboxylate transporter that feeds metabolites to the glyoxylate shunt particularly under conditions of oxidative stress. PsC23 is bacteriostatic at a concentration of 1.66 µM (25 µg ml -1 ) and shows a synergistic effect with both the classes of drugs at an effective concentration of 100-200 nM (1.5-3.0 µg ml -1 ) when co administered with them. In combination with meropenem the VHH completely cleared the infection from a neutropenic mouse with a carbapenem-resistant P. aeruginosa systemic infection. Blocking the glyoxylate shunt by PsC23 resulted in disruption of energy transduction due to a respiratory shift to the oxygen-depleted TCA cycle causing inhibition of efflux and increased free radical generation from carbapenems and β-lactams exerting a strong bactericidal effect that reversed the resistance to multiple unrelated drugs., (© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Background: Carbapenem resistance in Pseudomonas aeruginosa is a serious global health problem. We investigated the clonal distribution and its association with the carbapenem resistance mechanisms of carbapenem-non-susceptible P. aeruginosa isolates from three Korean hospitals., Methods: A total of 155 carbapenem-non-susceptible P. aeruginosa isolates collected between 2011 and 2019 were analyzed for sequence types (STs), antimicrobial susceptibility, and carbapenem resistance mechanisms, including carbapenemase production, the presence of resistance genes, OprD mutations, and the hyperproduction of AmpC β-lactamase., Results: Sixty STs were identified in carbapenem-non-susceptible P. aeruginosa isolates. Two high-risk clones, ST235 (N=41) and ST111 (N=20), were predominant; however, sporadic STs were more prevalent than high-risk clones. The resistance rate to amikacin was the lowest (49.7%), whereas that to piperacillin was the highest (92.3%). Of the 155 carbapenem-non-susceptible isolates, 43 (27.7%) produced carbapenemases. Three metallo-β-lactamase (MBL) genes, bla IMP-6 (N=38), bla VIM-2 (N=3), and bla NDM-1 (N=2), were detected. bla IMP-6 was detected in clonal complex 235 isolates. Two ST773 isolates carried bla NDM-1 and rmtB . Frameshift mutations in oprD were identified in all isolates tested, regardless of the presence of MBL genes. Hyperproduction of AmpC was detected in MBL gene-negative isolates., Conclusions: Frameshift mutations in oprD combined with MBL production or hyperproduction of AmpC are responsible for carbapenem resistance in P. aeruginosa . Further attention is required to curb the emergence and spread of new carbapenem-resistant P. aeruginosa clones.

Introduction: Development of multi-, extensively-, and pandrug-resistant (MDR, XDR, and PDR) strains of Pseudomonas aeruginosa remains a major problem in medical care. The present study evaluated the effect of antimicrobial photodynamic therapy (aPDT) as a monotherapy and in combination with colistin against P. aeruginosa isolates., Methods: Two P. aeruginosa isolates recovered from patients with respiratory tract infections were examined in this study. Minimum inhibitory concentration (MIC) of colistin was determined by the colistin broth disk elution (CBDE) and the reference broth microdilution (rBMD) methods. aPDT was performed using the photosensitizer (Ps) riboflavin at several concentrations and a light-emitting diode (LED) emitting blue light for different irradiation times with or without colistin at 1/2 × MIC concentration., Results: Both PA1 and PA2 isolates were identified as colistin-resistant P. aeruginosa with a MIC ≥4 μg/mL by the CBDE and MICs of 512 μg/mL and 256 μg/mL, respectively, by the rBMD. In aPDT, neither riboflavin nor LED light alone had antibacterial effects. The values of colony forming units per milliliter (CFU/mL) in both isolates were significantly reduced by LED + Ps treatments in a time-dependent manner (LED irradiation time) and dose-dependent manner (Ps concentration). In comparison with control, treatment with Ps (50 μM) + LED (120 s) and Ps (100 μM) + LED (120 s) resulted in 0.27 log 10  CFU/mL and 0.43 log 10  CFU/mL reductions in PA1, and 0.28 log 10  CFU/mL and 0.34 log 10  CFU/mL reductions in PA2, respectively, (P < 0.01). The best results were obtained after the combination of aPDT followed by colistin, which increased bacterial reduction, resulting in a 0.41-0.7 log 10  CFU/mL reduction for PA1 and 0.35-0.83 log 10  CFU/mL reduction for PA2 (P = 0.001)., Conclusions: This study suggests the potential implications of aPDT in combination with antibiotics, such as colistin for treatment of difficult-to-treat P. aeruginosa infections., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Pseudomonas aeruginosa (PA) is a widely prevalent opportunistic pathogen. Multiple resistant strains of PA have emerged from excessive or inappropriate use of antibiotics, making their eradication increasingly difficult. Therefore, the search for highly efficient and secure novel antimicrobial agents is crucial. According to reports, there is an increasing exploration of nanometals for antibacterial purposes. The antibacterial mechanisms involving the nanomaterials themselves, the release of ions, and the induced oxidative stress causing leakage and damage to biomolecules are widely accepted. Additionally, the study of the cytotoxicity of metal nanoparticles is crucial for their antibacterial applications. This article summarizes the types of metal nanomaterials and metal oxide nanomaterials that can be used against PA, their respective unique antibacterial mechanisms, cytotoxicity, and efforts made to improve antibacterial performance and reduce toxicity, including combination therapy with other materials and antibiotics, as well as green synthesis approaches., (© 2024 Wiley Periodicals LLC.)

Purpose: To describe the prevalence and antibiotic resistance profiles of Pseudomonas aeruginosa isolated from the Asia Cornea Society Infectious Keratitis Study (ACSIKS)., Methods: All bacterial isolates from ACSIKS underwent repeat microbiological identification in a central repository in Singapore. Minimum inhibitory concentration (MIC) determination was conducted for isolates of P. aeruginosa against thirteen antibiotics from 6 different classes, and categorized based on Clinical Laboratory Standard Institutes' reference ranges. The percentage rates of resistance (non-susceptibility) to each antibiotic included isolates of both intermediate and complete resistance. Multi-drug resistance (MDR) was defined as non-susceptibility to at least one agent in three or more antimicrobial classes., Results: Of the 1493 unique bacterial specimens obtained from ACSIKS, 319 isolates were of P. aeruginosa. The majority of isolates were from centers in India (n = 118, 37%), Singapore (n = 90, 28.2%), Hong Kong (n = 31, 9.7%) and Thailand (n = 30, 9.4%). The cumulative antibiotic resistance rate was the greatest for polymyxin B (100%), ciprofloxacin (17.6%) and moxifloxacin (16.9%), and lowest for cefepime (11.6%) and amikacin (13.5%). Isolates from India demonstrated the highest antibiotic resistance rates of all the centers, and included moxifloxacin (47.5%) and ciprofloxacin (39.8%). Forty-eight of the 59 MDR isolates also originated from India. Antibiotic resistance rates were significantly lower in the other ACSIKS centers, and were typically less than 10%., Conclusions: The antibiotic resistance profiles of P. aeruginosa varied between different countries. While it was low for most countries, substantial antibiotic resistance and a significant number of multi-drug resistant isolates were noted in the centers from India., (© 2024. The Author(s).)

Development of potent and broad-spectrum antimicrobial peptides (AMPs) could help overcome the antimicrobial resistance crisis. We develop a peptide language-based deep generative framework (deepAMP) for identifying potent, broad-spectrum AMPs. Using deepAMP to reduce antimicrobial resistance and enhance the membrane-disrupting abilities of AMPs, we identify, synthesize, and experimentally test 18 T1-AMP (Tier 1) and 11 T2-AMP (Tier 2) candidates in a two-round design and by employing cross-optimization-validation. More than 90% of the designed AMPs show a better inhibition than penetratin in both Gram-positive (i.e., S. aureus) and Gram-negative bacteria (i.e., K. pneumoniae and P. aeruginosa). T2-9 shows the strongest antibacterial activity, comparable to FDA-approved antibiotics. We show that three AMPs (T1-2, T1-5 and T2-10) significantly reduce resistance to S. aureus compared to ciprofloxacin and are effective against skin wound infection in a female wound mouse model infected with P. aeruginosa. In summary, deepAMP expedites discovery of effective, broad-spectrum AMPs against drug-resistant bacteria., (© 2024. The Author(s).)

Pseudomonas aeruginosa ( P. aeruginosa ) pneumonia can have serious physiological consequences, particularly when P. aeruginosa biofilms are formed. Although inhaled therapy is preferred, inhaled drugs tend to get trapped by pulmonary mucus, which hinders efficient antibiotic permeability through mucus and biofilms. In this study, we prepare poly[2-(pentamethyleneimino)ethyl methacrylate]- block -poly[2-( N -oxide-pentamethyleneimino)ethyl methacrylate] (PPEMA- b -PPOEMA) micelles loaded with azithromycin (AZM) using reversible addition-fragmentation chain transfer (RAFT) polymerization to achieve effective treatment of P. aeruginosa pneumonia. The zwitterionic structure on the surface of the micelle facilitates the successful traversal of the mucus and optimal concentration within the biofilm. Furthermore, the protonation of piperidine in the polymer enables the micelles to exhibit a positive charge in the acidic environment of a bacterial infection, enhancing AZM's interaction with the bacterium. Both in vivo and in vitro experiments demonstrate that this transmucosal zwitterionic polymer, in combination with a charge reversal strategy, effectively promotes the enrichment of micelles at the site of bacterial infection, thereby increasing the number of antibiotics reaching the bacterial interior and demonstrating remarkable antibacterial synergy. Overall, this work offers a promising approach for trans-airway drug delivery in the treatment of pneumonia.

Skin infections are a major threat to human health. Early diagnosis of bacterial infections is of great significance for implementing protective measures on the skin. Therefore, in this study, we designed an electrospun membrane (PPBT) for visual monitoring of colonized bacteria and responsive antibacterial ability. Specifically, the acidity of the microenvironment caused by bacterial metabolism was applied to drive the color change of bromothymol blue (BTB) on the PPBT membrane from green to yellow, thereby facilitating the early warning of infection and timely treatment. Within 4 h, different concentrations of Staphylococcus aureus (∼10 5 CFU mL -1 ), Escherichia coli (∼10 5 CFU mL -1 ), Pseudomonas aeruginosa (∼10 5 CFU mL -1 ) and Candida albicans (∼10 4 CFU mL -1 ) were visually monitored. Moreover, as the local acidity was enhanced via microbial metabolism, ZIF-8 nanoparticles loaded with TCS (TCS@ZIF-8) on the PPBT membrane could release TCS in an acid-responsive manner. At the same time, ROS were generated under 405 nm irradiation to achieve synergistic antibacterial ability. Experiments confirmed that the PPBT membrane has ideal and controllable antibacterial features based on acid responsive release and a synergistic photocatalytic antibacterial mechanism after monitoring. Therefore, the PPBT membrane developed in this work provides a feasible solution for bacterial monitoring and inactivation devices. More importantly, it can be beneficial for meeting the needs of clinical diagnosis and timely treatment of bacterial infection.

Arctium lappa (Burdock) root is used in various culinary applications especially in Asian Cuisine. Arctigenin (ARC) is a polyphenolic compound abundant in the roots of the burdock plant from which it derives its name. The emergence of bacterial resistance is a growing global worry, specifically due to the declining availability of new antibiotics. Screening for the antibacterial candidates among the safe natural products is a promising approach. The present study was aimed to assess the antibacterial activity of ARC against Pseudomonas aeruginosa exploring its effect on the bacterial cell membrane. Furthermore, the anti-virulence activities and anti-quorum sensing (QS) activities of ARC were in vitro, in vivo and in silico assessed against P. aeruginosa . The current results showed the ARC antibacterial activity was owed to its disruption effect of the cell membrane. ARC at sub-MIC significantly decreased the formation of biofilm, motility, production of extracellular enzymes and in vivo protected mice against P. aeruginosa . These anti-virulence activities of ARC are owed to its interference with bacterial QS and its expression. Furthermore, ARC showed mild effect on mammalian erythrocytes, low probability to induce resistance and synergistically combined with antibiotics. In summary, the promising anti-virulence properties of ARC indicate its potential as an effective supplement to conventional antibiotics for treating severe P. aeruginosa infections.

Background: Antibiotic resistance among Gram-negative bacteria in intensive care units (ICUs) is linked with high morbidity and mortality in patients. In this study, we estimated the therapeutic coverage of various antibiotics, focusing on cefiderocol and comparators, administered empirically against an infection of unknown origin in the ICU., Methods: In the ARTEMIS surveillance study, susceptibilities of 624 Italian Gram-negative isolates to amikacin, aztreonam-avibactam, cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, colistin, imipenem-relebactam, meropenem, and meropenem-vaborbactam were tested by broth microdilution, and results were interpreted by European Committee on Antimicrobial Susceptibility Testing breakpoints. The susceptibility rates from the ARTEMIS study were extrapolated to Gram-negative isolates obtained from 5,774 patients in Italian ICUs in 2021. The sum of the predicted susceptibilities of individual pathogens represented the overall likelihood of in vitro activity of each antibiotic as early targeted therapy for ICU patients., Results: A total of 624 Italian Gram-negative isolates included 206 Pseudomonas aeruginosa, 138 Acinetobacter baumannii, 187 Klebsiella pneumoniae, and 93 Escherichia coli. Against A. baumannii, K. pneumoniae, P. aeruginosa, and E. coli, the overall susceptibility rates for cefiderocol were 87.7%, 96.8%, 99%, and 100%, respectively; and for comparator agents, 8.7-96.4%, 25.7-100%, 73.3-100%, and 89.2-100%, respectively. Among the subset of meropenem-resistant isolates, susceptibility rates of A. baumannii, K. pneumoniae, and P. aeruginosa to cefiderocol were 86.4%, 96.2% and 100%, respectively. Corresponding susceptibility rates to comparator agents were 0-96.8%, 0-100%, and 6.4-100%, respectively. There were no meropenem-resistant isolates of E. coli. The extrapolation of data to isolates from Italian ICUs showed that the highest likelihood of therapeutic coverage, both overall and among meropenem-resistant isolates, was reported for colistin (96.8% and 72.2%, respectively) and cefiderocol (95.7% and 71.4%, respectively). All other antibiotics were associated with a likelihood below 73% overall and between 0% and 41.4% for meropenem-resistant isolates., Conclusions: Based on confirmed susceptibility rates and reported ICU prevalence of multiple Gram-negative species, cefiderocol showed a higher predicted therapeutic coverage and utility in ICUs compared with comparator beta-lactam-beta-lactamase inhibitor antibiotics. Cefiderocol may be a promising early treatment option for patients at high risk of carbapenem-resistant Gram-negative bacterial infections in the ICU., (© 2024. The Author(s).)

Background: More than a century has passed since it was discovered that many bacteria produce indole, but research into the actual biological roles of this molecule is just now beginning. The influence of indole on bacterial virulence was extensively investigated in indole-producing bacteria like Escherichia coli. To gain a deeper comprehension of its functional role, this study investigated how indole at concentrations of 0.5-1.0 mM found in the supernatant of Escherichia coli stationary phase culture was able to alter the virulence of non-indole-producing bacteria, such as Pseudomonas aeruginosa, Proteus mirabilis, and Klebsiella pneumoniae, which are naturally exposed to indole in mixed infections with Escherichia coli., Results: Biofilm formation, antimicrobial susceptibility, and efflux pump activity were the three phenotypic tests that were assessed. Indole was found to influence antibiotic susceptibly of Pseudomonas aeruginosa, Proteus mirabilis and Klebsiella pneumoniae to ciprofloxacin, imipenem, ceftriaxone, ceftazidime, and amikacin through significant reduction in MIC with fold change ranged from 4 to 16. Biofilm production was partially abrogated in both 32/45 Pseudomonas aeruginosa and all eight Proteus mirabilis, while induced biofilm production was observed in 30/40 Klebsiella pneumoniae. Moreover, acrAB and oqxAB, which encode four genes responsible for resistance-nodulation-division multidrug efflux pumps in five isolates of Klebsiella pneumoniae were investigated genotypically using quantitative real-time (qRT)-PCR. This revealed that all four genes exhibited reduced expression indicated by 2^-ΔΔCT < 1 in indole-treated isolates compared to control group., Conclusion: The outcomes of qRT-PCR investigation of efflux pump expression have established a novel clear correlation of the molecular mechanism that lies beneath the influence of indole on bacterial antibiotic tolerance. This research provides novel perspectives on the various mechanisms and diverse biological functions of indole signaling and how it impacts the pathogenicity of non-indole-producing bacteria., (© 2024. The Author(s).)

A biotransformation pair consisting of vinblastine: vincristine present in the Catharanthus roseus plant is of immense pharmacological significance. In this study, we successfully transformed vinblastine into vincristine outside the plant using Pseudomonas aeruginosa 8485 and Pseudomonas fluorescens 2421 and evaluated the antiangiogenic potential of thus produced vincristine through the CAM assay. The toxicity assay showed that both Pseudomonas spp. can tolerate varying concentrations (25-100 µl of 1 mg/ml) of vinblastine. The biotransformation was performed in a liquid nutrient broth medium containing vinblastine (25-100 µl), and Pseudomonas spp. inoculums (50-150 µl) by incubating at 30 °C and 37 °C, respectively for 8 days. The process was optimized for substrate and culture concentrations, pH, temperature, and rotation speed (rpm) for the highest conversion. Analysis using LC-MS/MS confirmed the presence of vincristine as a product of the vinblastine biotransformation by two Pseudomonas spp. P. fluorescens 2421 showed a faster conversion rate with 95% of vinblastine transformed within 24 h than P. aeruginosa 8485, which demonstrated a conversion rate of 92% on the 8 th day. From LC-MS/MS analysis, the optimal conditions for the reaction were determined as vinblastine (25 µl), microbial inoculums (150 µl or 200 × 10 6 and 210 × 10 6  CFU/ml), pH 7.4, rotation speed of 180 rpm, and temperatures of 30 °C and 37 °C with incubation time of 8 days. The vincristine produced exhibited potent antiangiogenic activity in the CAM assay reducing the thickness and branching of blood vessels in a dose-dependent manner. The study concludes that both Pseudomonas spp. showed promise for vincristine production from vinblastine, without compromising its antiangiogenic properties., (© 2024. The Author(s).)

Continuing our search for bioactive compounds in species from the Juncaceae family, Juncus articulatus was investigated. Ten previously undescribed phenanthrenes─articulins A-J ( 1 - 10 )─and ten known compounds─juncuenin B, dehydrojuncuenin B, juncatrin B, ensifolins E, F, H, I, K, juncuenin D, and luzulin A ( 11 - 20 )─along with other compounds, have been isolated and identified. The isolated compounds were evaluated for antibacterial activity against Escherichia coli , Pseudomonas aeruginosa , methicillin-susceptible Staphylococcus aureus (MSSA), and methicillin-resistant Staphylococcus aureus (MRSA). Compounds 12 and 14 exhibited the most potent activity against planktonic and sessile MSSA and MRSA with minimum inhibitory concentration (MIC) values of 15.1 μM ( 12 for both bacterial strains) and 15.3 μM ( 14 for both bacterial strains). Compounds 15 , 17 , and 18 also exhibited activity against both strains, although to a lower extent, with MIC values ranging from 30.0 to 56.8 μM. The inhibition of biofilm formation of these compounds was observed at 15.1-114.3 μM. This study elucidates the phenanthrene composition of J. articulatus and the antibacterial effect of these compounds.

The rise of drug resistance has become a global crisis, with >1 million deaths due to resistant bacterial infections each year. Pseudomonas aeruginosa, in particular, remains a serious problem with limited solutions due to complex resistance mechanisms that now lead to more than 32,000 multidrug-resistant (MDR) infections and over 2000 deaths in the U.S. annually. While the emergence of resistant bacteria has become ominously common, identification of useful new drug classes has been limited over the past over 40 years. We found that a potential novel therapeutic, the peptide-mimetic TM5, is effective at killing P. aeruginosa and displays sufficiently low toxicity in mammalian cells to allow for use in treatment of infections. Interestingly, TM5 kills P. aeruginosa more rapidly than traditional antibiotics, within 30-60 min in vitro, and is effective against a range of clinical isolates, including extensively drug resistant strains. In vivo, TM5 significantly reduced bacterial load in the lungs within 24 h compared to untreated mice and demonstrated few adverse effects. Taken together, these observations suggest that TM5 shows promise as an alternative therapy for MDR P. aeruginosa respiratory infections., (© 2024. The Author(s).)

Orthopedic implant-related bacterial infections and resultant antibiotic-resistant biofilms hinder implant-tissue integration and failure. Biofilm quorum sensing (QS) communication determines the pathogen colonization success. However, it remains unclear how implant modifications and host cells are influenced by, or influence, QS. High aspect ratio nanotopographies have shown to reduce biofilm formation of Pseudomonas aeruginosa , a sepsis causing pathogen with well-defined QS molecules. Producing such nanotopographies in relevant orthopedic materials (i.e., titanium) allows for probing QS using mass spectrometry-based metabolomics. However, nanotopographies can reduce host cell adhesion and regeneration. Therefore, we developed a polymer (poly(ethyl acrylate), PEA) coating that organizes extracellular matrix proteins, promoting bioactivity to host cells such as human mesenchymal stromal cells (hMSCs), maintaining biofilm reduction. This allowed us to investigate how hMSCs, after winning the race for the surface against pathogenic cells, interact with the biofilm. Our approach revealed that nanotopographies reduced major virulence pathways, such as LasR. The enhanced hMSCs support provided by the coated nanotopographies was shown to suppress virulence pathways and biofilm formation. Finally, we selected bioactive metabolites and demonstrated that these could be used as adjuncts to the nanostructured surfaces to reduce biofilm formation and enhance hMSC activity. These surfaces make excellent models to study hMSC-pathogen interactions and could be envisaged for use in novel orthopedic implants.

Preservative ingredients in cosmetic formulations undertake a necessary role in the prevention of microbial contamination. In this field, there is an unmet need for natural, sustainable, and effective preservatives. Thus, the main goal of this work was to evaluate a sugarcane straw extract-based ingredient and investigate its potential as a preservative for cosmetic applications. Different ingredients were developed using several cosmetic solvents to improve the solubility of the extracted compounds. The antimicrobial activity was assessed against Staphylococcus aureus , Escherichia coli , Pseudomonas aeruginosa , and Candida albicans . The 1,2-hexanediol was the solvent that allowed us to achieve the ingredient (20% dry extract dispersed in 25% 1,2-hexanediol in water) with the best antimicrobial performance, showing a minimum inhibitory concentration of between 5% and 3% ( I ). The 5% ( w / v ) concentration of this ingredient complied with the USP51 standards for cosmetic preservatives. Real-time (25 °C, 65% RH) and accelerated stability (40 °C, 75% RH) tests were conducted to determine the ingredient stability, and it was found that one month of storage time at room temperature would be ideal for better ingredient stability and performance in terms of composition, pH, color, and antioxidant activity.

Microbiologically Influenced Corrosion (MIC) poses a significant challenge to various industries, leading to substantial economic losses and potential safety hazards. Despite extensive research on the MIC resistance of various materials, there is a lack of studies focusing on High Chromium White Iron (HCWI) alloys, which are widely used in wear-resistant applications. This study addresses this knowledge gap by providing a comprehensive investigation of the MIC resistance of three HCWI alloys with varying chromium contents (22 wt%, 30.7 wt%, and 21 wt%) in the presence of Pseudomonas aeruginosa (P. Aeruginosa), a common bacterial species associated with MIC. The alloys were exposed to an artificial seawater medium inoculated with P.Aeruginosa for 14 days, and their corrosion behaviour was evaluated using electrochemical techniques, surface analysis, and microscopy. Electrochemical Impedance Spectroscopy (EIS) results revealed that the alloy with the highest chromium content (A2, 30.7 wt% Cr) exhibited superior MIC resistance compared to the other alloys (A1, 22 wt% Cr and M1, 21 wt% Cr). The enhanced performance of alloy A2 was attributed to the formation of a more stable and protective passive film, as well as the development of a more compact and less permeable biofilm. The EIS data, interpreted using equivalent circuit models, showed that alloy A2 had the highest charge transfer resistance and the lowest biofilm capacitance, indicating a more effective barrier against corrosive species. Bode plots further confirmed the superior corrosion resistance of alloy A2, with higher impedance values and phase angles at low frequencies compared to alloys A1 and M1. Scanning Electron Microscopy (SEM) and optical microscopy analyses corroborated these findings, showing that alloy A2 had the lowest pit density and size after 14 days of exposure. The insights gained from this study highlight the critical role of chromium content in the MIC resistance of HCWI alloys and have significant implications for the design and selection of materials for applications prone to microbial corrosion., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)