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Bacterial quorum sensing is a chemical language allowing bacteria to interact through the excretion of molecules called autoinducers, like N-acyl-homoserine lactones (AHLs) produced by Gram-negative Burkholderia and Paraburkholderia bacteria known as opportunistic pathogens. The AHLs differ in their acyl-chain length and may be modified by a 3-oxo or 3-hydroxy substituent, or C = C double bonds at different positions. As the bacterial signal specificity depends on all of these chemical features, their structural characterization is essential to have a better understanding of the population regulation and virulence phenomenon. This study aimed at enabling the localization of the C = C double bond on such specialized metabolites while using significantly lower amounts of biological material. The approach is based on LC–MS/MS analyses of bacterial extracts after in-solution derivatization by a photochemical Paternò-Büchi reaction, leading to the formation of an oxetane ring and subsequently to specific fragmentations when performing MS/MS experiments. The in-solution derivatization of AHLs was optimized on several standards, and then the matrix effect of bacterial extracts on the derivatization was assessed. As a proof of concept, the optimized conditions were applied to a bacterial extract enabling the localization of C = C bonds on unsaturated AHLs. [ABSTRACT FROM AUTHOR]

Ultrasonic-assisted synthesis of ZnO/TiO₂ and Fe₃O₄/TiO₂ bi-oxide nanocomposites at low frequencies (60 kHz) with their characterizations and antibacterial/antifungal applications are investigated in this study. Using nanotechnology as the next-generation solution, this research explored the potential of metal oxide nanoparticles as effective antibacterial agents. Nanomaterials were synthesized via a novel and facile method (sono-synthesis) and characterized using various techniques (XRD, SEM, FTIR, zeta potential analysis, Raman spectroscopy, and XPS), revealing nanoscale sizes of 25 nm for ZnO/TiO₂ and 31 nm for Fe₃O₄/TiO₂. Structural analysis demonstrated the distinct crystalline phases of the synthesized nanomaterials: TiO₂ with anatase structure (25 %), hexagonal wurtzite structure for ZnO, and Fe₃O₄ with inverse spinel structure, formed in nano-dimensions (19–31 nm) with a near-spherical shape. Antibacterial and antifungal assays highlighted the efficacy of both bi-nanocomposites against gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria, along with their potent activity against Candida albicans and non-albicans Candida. Moreover, principal component analysis (PCA) was used to identify potential relationships between the physicochemical properties (zeta potential, size, conductivity, and concentration) of all nanomaterials tested and their zone of inhibition (ZOI) against all bacterial species tested. Overall, this study emphasizes the novelty of employing a simple and efficient sono-synthetic route to synthesize ZnO/TiO₂ and Fe₃O₄/TiO₂ bi-nanocomposites and investigate their significant antibacterial and antifungal activities. Additionally, it identifies the potential relationships between the physicochemical properties of the nanomaterials tested and their antimicrobial activity. This approach provides a robust framework for future applications of bi-nanocomposites in combating microbial infections. • Effectively synthesized Fe₃O₄, ZnO, Fe₃O₄/TiO₂, and ZnO–TiO₂ bi-nanocomposites using an ultrasonic process via one-pot synthesis, while also uncovering their inherent antimicrobial potential. • The sono-synthesized nanomaterials were characterized and confirmed by various spectroscopic and microscopic techniques. • XRD confirmed the successful synthesis of bi-nanocomposites and showed the average crystallite size of Fe₃O₄/TiO₂ as 15.79 nm and ZnO/TiO₂ as 10.35 nm. • Particularly, Fe₃O₄/TiO₂ and Fe₃O₄ showed significant antimicrobial activity against both Gram-negative and Gram-positive bacteria. • Both Fe₃O₄/TiO₂ and ZnO/TiO₂ bi-nanocomposites exhibited remarkable antibacterial activity against E. coli and antifungal activity against non-albicans Candida, suggesting their effectiveness in combating fungal pathogens. [ABSTRACT FROM AUTHOR]

This study proposes inexpensive antimicrobial polyaniline-titanium oxide (PANI-TiO 2) samples prepared through eco-friendly enhanced microwave (MW) synthesis with 93 W applied over 10 min in aqueous 1.25 M hydrochloric acid media (HCl) using potassium iodate (KIO 3) as oxidising agent, an approach suitable for industrial scale up production of PANI polymers at room temperature. The PANI-TiO 2 samples are produced in the presence of 5–20 wt% of TiO 2 in the initial reaction mixture along with aniline monomer by both the enhanced MW method and a classical chemical synthesis (CS) method at room temperature. The nanocomposites showed lower conductivity than pure PANI, slightly higher conductivity was observed in the MW prepared PANI-TiO 2 in comparison to CS prepared PANI-TiO 2. This result can be correlated with the observation that the optical absorbance of MW PANI-TiO 2 samples were notable higher than for CS PANI-TiO 2 , which may be due to the presence of a greater amount of polarons present in the samples prepared by the enhanced MW method. MW PANI-TiO 2 samples were equally active against both Gram-negative E. coli and Gram-positive S. aureus bacteria, in contrast to the CS PANI-TiO 2 samples, which could be due to presence of short-chain fragments in the CS samples as confirmed by Fourier-transform infrared (FTIR) spectroscopy. The incorporation of PANI particles in TiO 2 showed enhanced antimicrobial activity compared to pure TiO 2 , with greater antifungal activity. Our study indicates that a facile, low-cost, and green enhanced MW method can be used for preparation of the advanced antimicrobial PANI-TiO 2 nanocomposites for biomedical applications. [Display omitted] [ABSTRACT FROM AUTHOR]

We demonstrate the rapid capture, enrichment, and identification of bacterial pathogens using Adaptive Channel Bacterial Capture (ACBC) devices. Using controlled tuning of device backpressure in polydimethylsiloxane (PDMS) devices, we enable the controlled formation of capture regions capable of trapping bacteria from low cell density samples with near 100% capture efficiency. The technical demands to prepare such devices are much lower compared to conventional methods for bacterial trapping and can be achieved with simple benchtop fabrication methods. We demonstrate the capture and identification of seven species of bacteria with bacterial concentrations lower than 1000 cells per mL, including common Gram-negative and Gram-positive pathogens such as Escherichia coli and Staphylococcus aureus. We further demonstrate that species identification of the trapped bacteria can be undertaken in the order of one-hour using multiplexed 16S rRNA-FISH with identification accuracies of 70–98% with unsupervised classification methods across 7 species of bacteria. Finally, by using the bacterial capture capabilities of the ACBC chip with an ultra-rapid antimicrobial susceptibility testing method employing fluorescence imaging and convolutional neural network (CNN) classification, we demonstrate that we can use the ACBC chip as an imaging flow cytometer that can predict the antibiotic susceptibility of E. coli cells after identification. [ABSTRACT FROM AUTHOR]

The syntheses of 3,4-dihydropyrimidin-2(1H)-ones by one-pot, three-component condensation of aldehydes, β-ketoesters and urea or thiourea have been made more simple and efficient by using 20 mol% hydrazine sulfate as catalyst. Aldehydes, β-ketoesters and urea are cyclocondensed in the presence of hydrazine sulfate to produce dihydropyrimidines in ethanol under reflux conditions. The advantages of using hydrazine sulfate as a catalyst over the traditional Biginelli reaction conditions include outstanding yields (80–91%) and a shorter (10–15 hours) reaction time. In order to evaluate the antibacterial efficiencies of the synthesized compounds, we have studied the inhibitions of microbial proliferation of both Gram-positive (Bacillus brevis) and Gram-negative (E. coli) bacterial strains in comparison to a control group. The microbial inhibitions occur in the range of 40–98% by different derivatives of dihydropyrimidinones. Molecular docking studies of the synthesized compounds have also been done using software tools such as SwissADME. [ABSTRACT FROM AUTHOR]

A copper-based metal-organic framework named NH2-Cu-MOF has been synthesized and utilized as an effective broad-spectrum antimicrobial material in this article. The obtained NH2-Cu-MOF exhibits satisfying antibacterial activity against both gram-positive bacteria (S. aureus and S. epidermidis) and gram-negative bacteria (E. coli and K. peneumoniae). Additionally, the biocompatibility of this NH2-Cu-MOF has been validated through animal studies, showing no significant adverse effects, thereby confirming its high biocompatibility. These findings prove that NH2-Cu-MOF has positive effects upon the treatment of bacteria-infected wounds, which holds great potential to be applied in biochemistry field. [ABSTRACT FROM AUTHOR]

AbstractNovel 2-imino-6-(aryldiazenyl)-2H-chromene-3-carboxamides 6a–e, 2-amino-4H-cyclopenta or benzo[b]thiophene-3-carboxamides 10a,b, 2,7-diaminopyrazolo[1,5-a]pyrimidine-6-carboxamides 13a–e, pyrimidine-5-carboxamides 14, 15 and 3-amino-1H-pyrazole-4-carboxamide 16 were synthesized from the reaction of 2-cyano-N-(1,3-dihydroxy-2-(hydroxyl-methyl) propan-2-yl) acetamide 2 with 4-arylazosalicylaldehydes 5a-e, cyclopentanone and/or cyclohexanone, guanidine derivatives and hydrazine hydrate, respectively. Some new compounds were evaluated for antibacterial activity in vitro, and exhibited good efficacy compared to gentamicin. Compound 4c showed greater activity against gram negative bacteria (Klebsiella pneumonia and Pseudomonas aeruginosa) than standard antibiotic. Compound 4c with two withdrawing groups also showed the higher activity (38.7 ± 0.6) against fungi (Candida albicans) than the Nystatin (20 ± 0.5). On the other hand, compounds 13a, 13c, and 13e have strong cytotoxic activity among the tested compounds in the three selected cancer cell lines (HePG2, MCF7 and Hela). Physicochemical characterization by Swiss ADME predication was also performed for some synthesized compounds exhibiting better biological and antimicrobial properties. [ABSTRACT FROM AUTHOR]

Postbiotics are the non-viable bacterial products or the low molecular weight metabolites produced by probiotics that have received considerable attention owing to their health promoting effects. The present study aimed to investigate the safety and antibacterial properties of postbiotic components of Lacticaseibacillus rhamnosus (Lra) and Limosilactobacillus reuteri (Lre) for their potential applications in food products. The freeze dried postbiotic metabolites (FD-P) from Lra and Lre were extensively analyzed for their physico-chemical properties and antibacterial actions against common food borne pathogens. Higher levels of total flavonoids (1971.79 ± 20 mg Qu/ g), total short-chain fatty acid (23 µg/g), sugar contents, CAT, and SOD anti-oxidative enzymes were detected in the Lra postbiotic, while GSH-px levels and riboflavin were higher in Lre postbiotics (P < 0.01). No significant differences were recorded in the total phenolic (2501 and 2518 mg GAE/ L) and crude protein contents (305. 58 and 296.23 µg/g) of the postbiotics (p ≥ 0.05), respectively. Both FD-P samples showed enhanced activities against Gram-Positive pathogens compared to Gram-Negative pathogens (p < 0.05), while combining the two postbiotics further potentiated the antibacterial actions. Both FD-P samples were non-hemolytic to human erythrocyte cells, and exhibited low cytotoxicity in MRC 5 and IPEC-J2 cell lines at the highest used concentrations (150 mg/ml). In summary, the postbiotics derived from Lra and Lre are safe bioactive ingredients with enhanced antibacterial and antioxidant capabilities, having potential applications as a natural preservatives in food system, potentially enhancing safety and extending the shelf life of food products. [ABSTRACT FROM AUTHOR]

Introduction: Gram-negative bacteremia is a life-threatening infection with high morbidity and mortality. Its incidence is rising worldwide, and treatment has become more challenging due to emerging bacterial resistance. Little data is available on the burden and outcome of such infections in Lebanon. Methods: We conducted this retrospective study in four Lebanese hospitals. Data on medical conditions and demographics of 2400 patients diagnosed with a bloodstream infection based on a positive blood culture were collected between January 2014 and December 2020. Results: Most bacteremias were caused by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii, with the more resistant organisms being hospital-acquired. Third-generation cephalosporin and quinolone resistance was steady throughout the study, but carbapenem resistance increased. Mortality with such infections is high, but carbapenem resistance or infection with Pseudomonas or Acinetobacter species were significant risk factors for poor outcomes. Conclusion: This is the first multi-center study from Lebanon on gram-negative bacteremia, resistance patterns, and factors associated with a poor outcome. More surveillance is needed to provide data to guide empirical treatment for bacteremia in Lebanon. [ABSTRACT FROM AUTHOR]

Lipopolysaccharides (LPS) confer resistance against harsh conditions, including antibiotics, in Gram-negative bacteria. The lipopolysaccharide transport (Lpt) complex, consisting of seven proteins (A-G), exports LPS across the cellular envelope. LptB2FG forms an ATP-binding cassette transporter that transfers LPS to LptC. How LptB2FG couples ATP binding and hydrolysis with LPS transport to LptC remains unclear. We observed the conformational heterogeneity of LptB2FG and LptB2FGC in micelles and/or proteoliposomes using pulsed dipolar electron spin resonance spectroscopy. Additionally, we monitored LPS binding and release using laser-induced liquid bead ion desorption mass spectrometry. The β-jellyroll domain of LptF stably interacts with the LptG and LptC β-jellyrolls in both the apo and vanadate-trapped states. ATP binding at the cytoplasmic side is allosterically coupled to the selective opening of the periplasmic LptF β-jellyroll domain. In LptB2FG, ATP binding closes the nucleotide binding domains, causing a collapse of the first lateral gate as observed in structures. However, the second lateral gate, which forms the putative entry site for LPS, exhibits a heterogeneous conformation. LptC binding limits the flexibility of this gate to two conformations, likely representing the helix of LptC as either released from or inserted into the transmembrane domains. Our results reveal the regulation of the LPS entry gate through the dynamic behavior of the LptC transmembrane helix, while its β-jellyroll domain is anchored in the periplasm. This, combined with long-range ATP-dependent allosteric gating of the LptF β-jellyroll domain, may ensure efficient and unidirectional transport of LPS across the periplasm. [ABSTRACT FROM AUTHOR]

AbstractPseudomonas aeruginosa is a versatile Gram-negative pathogen known for its ability to invade the respiratory tract, particularly in cystic fibrosis patients. This review provides a comprehensive analysis of the multifaceted strategies for colonization, virulence, and immune evasion used by P. aeruginosa to infect the host. We explore the extensive protein arsenal of P. aeruginosa, including adhesins, exotoxins, secreted proteases, and type III and VI secretion effectors, detailing their roles in the infective process. We also address the unique challenge of treating diverse lung conditions that provide a natural niche for P. aeruginosa on the airway surface, with a particular focus in cystic fibrosis. The review also discusses the current limitations in treatment options due to antibiotic resistance and highlights promising future approaches that target host-pathogen protein-protein interactions. These approaches include the development of new antimicrobials, anti-attachment therapies, and quorum-sensing inhibition molecules. In summary, this review aims to provide a holistic understanding of the pathogenesis of P. aeruginosa in the respiratory system, offering insights into the underlying molecular mechanisms and potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to characterize bacterial species, aetiology and antibiotic susceptibility connected to bacterial keratitis infections in Östergötland, Sweden. Methods: Retrospective cross-sectional study based on electronic health records for the period 2010–2019. Records of patients diagnosed with infectious keratitis were screened for microbiology confirmed infectious bacterial keratitis. Bacterial species and their susceptibility to antibiotics were determined from microbiology test results. Results: One-hundred and ninety patients with lab culture-confirmed infectious bacterial keratitis were included in the analysis. The most frequently found bacterial species were coagulase-negative staphylococci (39%), Staphylococcus aureus (17%) and Cutibacterium acnes (10%). Pseudomonas spp. was the most frequently found Gram-negative bacterial species (7%). Contact lens wear and severely ill/blind eye were the top two aetiologies associated with bacterial keratitis, 22% of the patients with bacterial keratitis were also diagnosed with glaucoma. Most isolates, 157 out of 173, were susceptible to fluoroquinolones, and 145 out of 155 isolates were susceptible to chloramphenicol. Conclusion: Our results revealed a positive rate of bacterial keratitis of 59% for the samples sent to the laboratory. There was a high susceptibility of the bacterial species to the recommended antibiotics. Our results indicate that it is likely that patients are receiving the correct treatment. Future studies are necessary to monitor changes in antibiotic susceptibility. [ABSTRACT FROM AUTHOR]

This study aimed to optimize the production of carotenoid pigments from Micrococcus luteus (ATCC 9341) through the statistical screening of media components and the characterization of antimicrobial, antioxidant, cytogenetic and cytotoxic activities. A BOX-Behnken design was used to assess the effects of whey concentration, inoculum size, pH, temperature, and agitation speed on carotenoid yield. The optimum combination increased production to 2.19 g/L, with a productivity of 0.045 g L-1 h−1 and a productivity yield of 0.644 g/g, as confirmed by an observed carotene production of 2.19 g/L. The final response surface model fitting the data had an R2 of 0.9461. High-performance liquid chromatography (HPLC) analysis identified 12 carotenoid pigment compounds produced by M. luteus. The extracts displayed moderate antimicrobial efficacy against Gram-positive bacteria such as Bacillus cereus (ATCC 11778), Staphylococcus aureus (ATCC 6538), and E. faecalis (ATCC 19433), with inhibition zone diameters (IZD) of 29.0, 14.0, and 37.0 mm, respectively, at 1000 μg/mL. However, its effectiveness against Gram-negative bacteria is limited. In comparison, tetracycline exhibited greater antimicrobial potency. The IC50 value of carotenoids was used to indicate the antioxidant activity. IC50 value from the DPPH assay was 152.80 mg/100mL. An IC50 cytotoxicity value greater than 300 μg/mL was found against normal mouse liver cells, with over 68% cell viability even at 300 μg/mL, indicating low toxicity. Histological structure studies revealed normal myocardial muscle tissue, lung tissue, and kidney tissue sections, whereas liver tissue sections revealed ballooning degeneration of hepatocytes and disorganization of hepatic cords. Cytogenetic parameters revealed that the carotene treatment group had a mitotic index (70%) lower than that of the control but higher than that of the positive control, mitomycin, and did not substantially increase numerical (1.2%) or structural aberrations compared with those of the control, suggesting a lack of genotoxic effects under the experimental conditions. In conclusion, optimized culture conditions enhanced carotenoid yields from M. luteus, and the extracts displayed promising bioactivity as moderate antibiotics against certain gram-positive bacteria and as antioxidants. The high IC50 values demonstrate biosafety. Overall, this bioprocess for enhanced carotenoid production coupled with bioactivity profiling and low cytotoxicity support the application of M. luteus carotenoids. [ABSTRACT FROM AUTHOR]

Bacterial soft rots are among the most economically important diseases that cause significant yield losses in various crops. During 2022 and 2023, widespread occurrence of soft rot disease was observed in sugar beet fields in the Firuzan region, Hamedan Province, Iran. From the sugar beet plants with soft rot symptoms, a bacterial isolate was obtained that was obligately aerobic, negative for Gram, oxidase, levan, and arginine dihydrolase tests, and positive for pectinase, urease and hypersensitivity reaction on tobacco. Koch's postulates confirmed its pathogenicity by developing soft rot symptoms in sugar beet plants. The 16SrRNA and rpoD sequences from this isolate were most closely related to Pseudomonas punonensis LMT03 with 99.8% and 94.7% identity, respectively and then to Pseudomonas argentinensis LMG22563 (= CH01) with 99.4% and 94.3% identity values. To our knowledge, this is the first report of a Pseudomonas sp. strain causing soft rot disease in sugar beet worldwide. [ABSTRACT FROM AUTHOR]

Gram-negative bacteria produce chaperone-usher pathway pili, which are extracellular protein fibers tipped with an adhesive protein that binds to a receptor with stereochemical specificity to determine host and tissue tropism. The outer-membrane usher protein, together with a periplasmic chaperone, assembles thousands of pilin subunits into a highly ordered pilus fiber. The tip adhesin in complex with its cognate chaperone activates the usher to allow extrusion across the outer membrane. The structural requirements to translocate the adhesin through the usher pore from the periplasm to the extracellular space remains incompletely understood. Here, we present a cryoelectron microscopy structure of a quaternary tip complex in the type 1 pilus system from Escherichia coli, which consists of the usher FimD, chaperone FimC, adhesin FimH, and the tip adapter FimF. In this structure, the usher FimD is caught in the act of secreting its cognate adhesin FimH. Comparison with previous structures depicting the adhesin either first entering or having completely exited the usher pore reveals remarkable structural plasticity of the two-domain adhesin during translocation. Moreover, a piliation assay demonstrated that the structural plasticity, enabled by a flexible linker between the two domains, is a prerequisite for adhesin translocation through the usher pore and thus pilus biogenesis. Overall, this study provides molecular details of adhesin translocation across the outer membrane and elucidates a unique conformational state adopted by the adhesin during stepwise secretion through the usher pore. This study elucidates fundamental aspects of FimH and usher dynamics critical in urinary tract infections and is leading to antibiotic-sparing therapeutics. [ABSTRACT FROM AUTHOR]

Objective: The most comprehensive collection of imine was synthesized via a simple, efficient, economical, and rapid method via Schiff base formation. Methods: ((E)-1,5-dimethyl-2-phenyl-4-(((2-phenylimidazo[1,2-a]pyridine-3-yl)methylene)amino)-1,2-dihydro-3H-pyrazol-3-one and their derivatives are synthesized using 4-aminoantipyrine and some substituted 2-phenylimidazo[1,2-a]pyridine-3-carbaldehyde derivatives (SB01) to (SB10). Results and Discussion: The newly synthesized molecules were confirmed using various analytical techniques MS, FT-IR, 1H, and 13C NMR spectrometric analyses. Newly synthesized imidazo[1,2-a]pyridine compounds undergo their biological evaluation with Gram-positive and Gram-negative bacteria as well as antifungal. Conclusions: (SB10), (SB07), (SB05), and (SB01) molecules show good, moderate, and excellent results against tested drugs. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to clarify the difference in Fusobacterium nucleatum (F. nucleatum) induced inflammatory cytokines and nod‐like receptor protein 3 (NLRP3) inflammasomes dysregulation among three periodontal cells. Methods: Oral epithelial cells (HIOECs), THP‐1 macrophages, and human gingival fibroblasts (HGFs) were exposed to F. nucleatum with/without adenosine triphosphate (ATP) and nigericin (Nig). Cell morphology was assessed by scanning electron microscopy. qRT‐PCR, protein microarrays, and bioinformatic methods were used to evaluate the cytokines and their complex interplay. NLRP3 inflammasomes activation was detected by western blotting and ELISA. Results: F. nucleatum adhered to and invaded cells. In HIOECs, F. nucleatum enhanced interleukin (IL)‐1α/1β/6/10/13, TNF‐α, and interferon (IFN)‐γ expression. In THP‐1 macrophages, F. nucleatum up‐regulated IL‐1α/1β/6/10 and TNF‐α levels. In HGFs, F. nucleatum increased IL‐6 levels. F. nucleatum and ATP synergistically boosted IFN‐γ level in THP‐1 macrophages and IL‐13 level in HGFs. IL‐1α/1β/6, and TNF‐α served as epicenters of the inflammatory response. Additionally, F. nucleatum activated NLRP3 inflammasomes in HIOECs, and ATP/Nig boosted the activation. F. nucleatum also triggered NLRP3 inflammasomes in THP‐1 macrophages, but in HGFs, only NLRP3 and caspase‐1 levels were elevated. Conclusion: F. nucleatum infiltrated periodontal supporting cells and dysregulated inflammatory cytokines and NLRP3 inflammasomes. [ABSTRACT FROM AUTHOR]

Carbapenem resistance in Acinetobacter baumannii is a critical global health threat attributed to transferrable carbapenemase genes. Carbapenemase genotyping using polymerase chain reaction (PCR) presents a challenge in resource-limited settings because of its technical requirements. This study designed new loop-mediated isothermal amplification (LAMP) primers using multiple sequence alignment-based workflows, validated the primer performance against multiple target variants in silico, and developed novel LAMP assays (LAntRN-OXA23 and LAntRN-ISAba1) to detect the transferable blaOXA-23-like carbapenemase genes and ISAba1 elements in pure cultures and A. baumannii-spiked serum samples. The designed LAMP primers bind to the conserved regions of their highly polymorphic targets, with their in silico performance comparable with other published primers. The in vitro LAMP assays (using 30 PCR-profiled A. baumannii and 10 standard multidrug-resistant gram-negative isolates) have 100% concordance with the PCR-positive clinical samples, limits of detection as low as 1 pg/µL (200 copies/µL), and specificities of 57.89–100%. Both assays produced positive results when testing DNA samples (extracted using a commercial kit) from blaOXA-23-like and ISAba1-blaOXA-51-like PCR-positive A. baumannii-spiked normal human sera (five set-ups per target). In summary, the LAMP assays accurately detected the target genes and have applications in infection management, control, and point-of-care testing in resource-limited healthcare settings. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae, a Gram-negative bacterium that has emerged as a significant global threat, has been implicated in nosocomial infections. The objectives of this investigation encompassed: i) assessment of extended spectrum ß-lactamase (ESBL) synthesis and other forms of antibiotic resistance, ii) characterization of biofilm formation, adhesin (fimH), and capsule (uge) virulence genes, and iii) exploration of the existence of Class-1 integron (intI1) within the isolates. A total of 120 K. pneumoniae were obtained from clinical specimens and identified with automatic Vitek®2 compact systems. The rates of resistance to various antibiotics were as follows: levofloxacin 89.1%, amoxicillin-clavulanic acid 69.1%, ceftazidime 60%, fosfomycin 59.1%, aztreonam 57.5%, nalidixic acid 56.6%, piperacillin-tazobactam 54.1%, tobramycin 44.1%, chloramphenicol 40%, gentamycin and meropenem 39.1%, imipenem 35.8%. Combined disc testing identified 28 isolates (23.3%) as ESBL-producing K. pneumoniae. The frequency of genes encoding ESBLs is reported as follows: blaTEM 10 (8.3%), blaSHV 42 (35%), and blaCTX-M-I 23 (19.1%). The virulence genes encountered in isolates were adhesin and capsule, 22.5% fimH and 21.6% uge, respectively. The intI1 gene was detected in 70 (58.3%) isolates. Biofilm analysis revealed that 58 isolates (48.3%) were biofilm producers. This study is important for preventing K. pneumoniae infection as it reveals the relationship between antibiotic resistance of isolates, virulence factors, and biofilm formation. [ABSTRACT FROM AUTHOR]

Introduction L-asparaginase is considered to be the most important component in the treatment of acute lymphoblastic leukemia (ALL). Intensifying the use of Lasparaginase during treatment for ALL has resulted in a significant rise in the percentage of children and adolescents who are cured of the disease. Asparaginase trough activity more than or equal to 100 IU/L on day 7 has been found to be the desired activity level in all childhood leukemia patients. Objectives Due to the paucity of data on biosimilar pegaspargase in the upfront setting, we planned this prospective pilot study to evaluate the levels of serum asparaginase activity (SAA) after biosimilar pegaspargase infusion. Materials and Methods It is a prospective, single-center, pilot study of 10 pediatric ALL patients for the duration of 6 months. All children less than 18 years with ALL on treatment with curative intent and receiving pegaspargase and who provided informed consent were included in this study. The enzymatic spectrophotometric method was used to determine SAA, and it was measured on the 7th and 14th days after the first dosage of pegaspargase-asparaginase, as well as on the 14th day after the second dose of pegaspargase-asparaginase, while toxicity was charted according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results From 10 patients with a median age of 5.5 years, a grand total of 29 samples were taken for analysis. Children who received pegaspargase had either B-ALL or T-ALL. After the first dose, mean-SD (standard deviation), SAA levels at day 7 was 131.3±38 IU/L and at Day 14 was 94.8±8 IU/L. After the second dose, mean±SD SAA level at day 14 was 86.1±15 IU/L. No patient had clinical hypersensitivity reaction and no patient reported any asparaginase-related toxicity. One patient died due to sepsis, infection with multidrug-resistant gram-negative bacteria. Conclusions Biosimilar pegaspargasemaintained good SAA levels 7 and 14 days after infusion. [ABSTRACT FROM AUTHOR]

Introduction: Extracorporeal membrane oxygenation (ECMO) is an organ support whose use is increasing in acute respiratory distress syndrome (ARDS) cases where adequate gas exchange cannot be achieved despite mechanical ventilation. Patients who were followed up on ECMO are at risk for developing nosocomial infections. In this study, we aimed to investigate the incidence of nosocomial infection and define isolated pathogens from microbiological samples in a single center in Turkey. Methods: Patients who were followed up on ECMO due to ARDS between January 1, 2018, and December 31, 2021, were included in the study. Nosocomial infections that were diagnosed after the first 48 h of ECMO cannulation and after 48 h of ECMO decannulation were accepted as ECMO-related infections. Results: A total of 50 patients with ARDS were followed up with ECMO. Mean age of patients was 46,8 ± 15,4 and 38 (78%) patients were male. A total of 30 patients (60%) had at least one nosocomial infection, for a rate of 37.6 per 1000 ECMO days. COVID-19, steroid treatment, and ECMO duration were found to be associated with nosocomial infections in patients who underwent ECMO support. In multivariate analysis, antibiotic use was found to be protective against nosocomial infection (OR:0.14, 95% CI: 0.03 – 0.70, p =.017). In addition, prolonged ECMO duration was associated with an increased risk of nosocomial infection in multivariate analysis (OR:1.13, 95% CI: 1.03 – 1.23, p =.010). Gram-negative pathogens were isolated dominantly in blood cultures and tracheal secretion samples, followed by fungi and Gram-positive bacteria. Conclusion: Patients are prone to nosocomial infections during ECMO. Microorganisms causing nosocomial infections in ECMO patients seem similar to the flora of each center, and this should be taken into account in the choice of empirical antibiotics. [ABSTRACT FROM AUTHOR]

The chemical composition, antimicrobial, and antibiofilm activities of the essential oil from the fruits of Turkish endemic Prangos hulusii were studied. Essential oil was analyzed by GC and GC/MS. Thirty-nine compounds were identified, which represent 98.6% of the total composition of the essential oil. Monoterpene hydrocarbons and sesquiterpene hydrocarbons were the most represented classes of volatiles with 49.8% and 21.0%, respectively. The main constituents of the essential oil were (E)-methyl cinnamate (22.9%), α-phellandrene (13.8%), and (E)-β-ocimene (12.9%). (E)-methyl cinnamate was detected in Prangos spp. for the first time. Antimicrobial activities against three Gram-positive bacteria, three Gram-negative bacteria, and three yeast strains were evaluated using disk diffusion test and microdilution method. Antibiofilm experiments were done by spectrophotometric microplate method and the results of Staphylococcus aureus, Escherichia coli, and Candida albicans were visualized via scanning electron microscopy. The essential oil had an antimicrobial effect and showed an antibiofilm effect on these strains. [ABSTRACT FROM AUTHOR]

Signaling systems of microorganisms are responsible for regulating the physiological and metabolic processes and also play vital roles in the communications of cells. Identifying signaling molecules mediating the cross-talks is challenging yet highly desirable for comprehending the microbial interactions. Here, we demonstrate that a pathogenic Gram-negative Chromobacterium violaceum exerts significant influence on the morphological differentiation and secondary metabolism of Gram-positive Streptomyces. The physiological metabolisms are directly modulated by three novel cinnamoyl lipids (CVCL1, 2, and 3) from C. violaceum CV12472, whose biosynthesis is under the control of N-acylhomoserine lactone signaling system. Furthermore, a receptor of CVCLs in Streptomyces ansochromogenes 7100 is determined to be SabR1, the cognate receptor of γ-butenolide signaling molecules. This study reveals an unprecedented mode of microbial interactions, and the quorum sensing signaling systems in these two groups of bacteria can be bridged via CVCLs, suggesting that CVCLs can modulate the physiological metabolism of cross-phylum microorganisms. Novel cinnamoyl lipids from Chromobacterium are found to modulate the physiological metabolism of Streptomyces via binding to the γ-butenolide signaling molecule receptor, representing an unprecedented mode of cross-phylum microbial interactions. [ABSTRACT FROM AUTHOR]

The use of nanoparticles (NPs) as an alternative to the current generation of conventional antibiotics has exploded in the research community in recent years, as evidence of the superiority of NPs over antibiotics in the treatment of pathogens has been steadily presented. However, therapy with NPs may result in the removal of both multidrug-resistant (MDR) pathogens and commensal bacteria due to the broad-spectrum activity of NPs and the non-specificity of target bacteria. Therefore, the fabrication of MDR-pathogen-targeting NPs is necessary. In this study, biogenic silver nanoparticles (Bio-AgNPs) were synthesized using bacterial cell-free supernatant from three communicating gram-negative bacteria. The size, physical features, and morphology of the AgNPs were characterized by dynamic light scattering (an average size of 158–168 nm), X-ray diffraction (co-ordinate patterns), and transmission electron microscopy (spherical structure). The antibacterial activity of the Bio-AgNPs as minimum inhibitory concentration values was obtained between 0.8 and > 6.4 μg mL−1 for bacterial strains. Mechanistic studies of Bio-AgNPs have revealed that biofilm inhibition, protein leakage, hyperproduction of reactive oxygen species, and physical cell damage are plausible mechanisms underlying the activity of Bio-AgNPs against gram-negative pathogens. Overall, the Bio-AgNPs synthesized in this study may bolster the potential use of Bio-AgNPs as a stand-in for traditional antibiotics, and offer potential specificity against bacterial targets. [ABSTRACT FROM AUTHOR]

Deep eutectic solvents have attracted considerable attention due to their economic and environmental benefits. This study investigates the role of reactive DESs in the synthesis of polyurethane coatings. DESs synthesized from Tetrabutylammonium bromide (TBAB) as a hydrogen-acceptor and Poly (ethylene glycol) and Ascorbic acid (AA) as hydrogen-donors, were used as assistant platforms and reactive agents for the synthesis of new biodegradable crosslinked PU-coatings via a solvent-free process. Cured PUs were characterized by FTIR, DSC, TGA, and DMTA techniques, as well as gel-content, swelling-index, biodegradation, scratch, and hardness tests. The results show that these DESs have played a splendid multi-task role that acted as non-volatile solvents and reactive monomers as well. They also facilitated curing reaction, improved flexibility, biodegradability, swelling-index, and resistance to scratch of PU-based DESs compared to pristine PU. PU samples synthesized in the presence of [DES]PEG/TBAB (P2) and [DES]AA/TBAB (P3) showed increased flexibility and damping properties (78, 26 Shore D—0.9, 1.3 Tanδ), biodegradability (81%, 60%), swelling-index (105%, 150%) and scratch resistance (3.8, 4.5 N), by about 69%, 52%, 36%, 48%, and 26% compared to the control sample (P1), respectively. Agar diffusion tests showed antibacterial activity of PU-DESs against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. This research highlights DESs as promising platforms to enhance the properties of PU coatings for the creation of eco-friendly, high-performance antiseptic coatings. [ABSTRACT FROM AUTHOR]

Lipooligosaccharides are the most abundant cell surface glycoconjugates on the outer membrane of Gram-negative bacteria. They play important roles in host–microbe interactions. Certain Gram-negative pathogenic bacteria cap their lipooligosaccharides with the sialic acid, N -acetylneuraminic acid (Neu5Ac), to mimic host glycans that among others protects these bacteria from recognition by the hosts immune system. This process of molecular mimicry is not fully understood and remains under investigated. To explore the functional role of sialic acid-capped lipooligosaccharides at the molecular level, it is important to have tools readily available for the detection and manipulation of both Neu5Ac on glycoconjugates and the involved sialyltransferases, preferably in live bacteria. We and others have shown that the native sialyltransferases of some Gram-negative bacteria can incorporate extracellular unnatural sialic acid nucleotides onto their lipooligosaccharides. We here report on the expanded use of native bacterial sialyltransferases to incorporate neuraminic acids analogs with a reporter group into the lipooligosaccharides of a variety of Gram-negative bacteria. We show that this approach offers a quick strategy to screen bacteria for the expression of functional sialyltransferases and the ability to use exogenous CMP-Neu5Ac to decorate their glycoconjugates. For selected bacteria we also show this strategy complements two other glycoengineering techniques, Metabolic Oligosaccharide Engineering and Selective Exo-Enzymatic Labeling, and that together they provide tools to modify, label, detect and visualize sialylation of bacterial lipooligosaccharides. [ABSTRACT FROM AUTHOR]

The potential of new genetically modified recombinant endolysins as antimicrobial agents against Gram-negative bacteria was investigated. A series of enzymes based on LysSi3 lysozyme-like muramidase was obtained by modifying its sequence with antimicrobial peptides of different families, and recombinant expression in E. coli was demonstrated. Modification of LysSi3 resulted in increased bacteriolytic activity against the model isolate of A. baumannii and a higher kinetics rate compared to the native enzyme. The cytotoxic properties of the newly engineered lysins were investigated with the HEK293 and HaCaT cell lines, and it was shown that modification of LysSi3 with antimicrobial peptides does not significantly increase the toxic properties in vitro. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. The objective of this study was to describe the prevalence of antimicrobial resistance of Escherichia coli , Klebsiella oxytoca , Klebsiellapneumoniae , and Serratiamarcescens from quarter milk samples submitted to the udder health laboratory of the Bavarian Animal Health Services (TGD) in Southern Germany between 2014 and 2022. All samples were tested with the California Mastitis Test and analyzed with a standard microbroth dilution to determine the MIC. The antimicrobials tested were amoxicillin/clavulanate, cefazoline, kanamycin/cefalexin, cefoperazone, cefquinome, and marbofloxacin. Breakpoints were chosen in accordance with the Clinical and Laboratory Standards Institute (CLSI). Over the study period, E. coli , K. oxytoca , and K. pneumoniae showed only few resistances to all antimicrobials tested. For those pathogens MIC 50 and MIC 90 were below breakpoint for all antimicrobials except cefoperazone over the 9 years. A decrease in MIC could be seen for E. coli and K. oxytoca for all of the antimicrobials. While the MIC for K. pneumoniae stayed more stagnant, the prevalence of resistance still decreased overall. Serratiamarcescens isolates were proven intrinsically resistant to amoxicillin/clavulanate and cefazolin, and while in vitro resistances were low for all other antimicrobials tested, S. marcescens tended toward higher MIC for most of the antimicrobials over the years. Over time, there was also an overall increase in the number of isolates for all 4 pathogens per year. Starting 2018 there was a steep increase in the number of isolates particularly from clinical cases. This jump in numbers coincided with a change of the regulation for veterinary drug prescriptions in Germany in 2018 that required, among other things, antimicrobial resistance testing before a change of antibiotics in the course of treatment and the use of critically important antimicrobials. Overall, although the pathogens increased in numbers, the prevalence of their antimicrobial resistance remained low. [ABSTRACT FROM AUTHOR]

Purpose: Colistin is used as a last resort antibiotic against infections caused by multidrug-resistant gram-negative bacteria, especially carbapenem-resistant bacteria. However, colistin-resistance in clinical isolates is becoming more prevalent. Cinnamaldehyde and baicalin, which are the major active constituents of Cinnamomum and Scutellaria, have been reported to exhibit antibacterial properties. The aim of this study was to evaluate the capacity of cinnamaldehyde and baicalin to enhance the antibiotic activity of colistin in Enterobacterales and Acinetobacter baumannii strains. Methods: The MICs of colistin were determined with and without fixed concentrations of cinnamaldehyde and baicalin by the broth microdilution method. The FIC indices were also calculated. In addition, time-kill assays were performed with colistin alone and in combination with cinnamaldehyde and baicalin to determine the bactericidal action of the combinations. Similarly, the effects of L-arginine, L-glutamic acid and sucrose on the MICs of colistin combined with cinnamaldehyde and baicalin were studied to evaluate the possible effects of these compounds on the charge of the bacterial cell- wall. Results: At nontoxic concentrations, cinnamaldehyde and baicalin partially or fully reversed resistance to colistin in Enterobacterales and A. baumannii. The combinations of the two compounds with colistin had bactericidal or synergistic effects on the most resistant strains. The ability of these agents to reverse colistin resistance could be associated with bacterial cell wall damage and increased permeability. Conclusion: Cinnamaldehyde and baicalin are good adjuvants for the antibiotic colistin against Enterobacterales- and A. baumannii-resistant strains. [ABSTRACT FROM AUTHOR]

Purpose: This study examines the incidence of infection and resistance associated with Intracorneal Ring Segment (ICRS) implantation, a common outpatient surgical treatment for correcting refractive errors and corneal ectatic diseases. Although ICRS procedures are typically safe and reversible, there is a low but notable risk of microbial infections, which require prompt and sometimes invasive treatment. Methods: Three electronic databases, PubMed, Web of Science (WoS), and Scopus, were utilised to search for literature according to PRISMA guidelines to identify infections related to the implantation of ICRS in the cornea between January 2000 and December 2022. Results: Gram-positive organisms were involved in 86% of cases: 35.7% S. aureus, 25% coagulase-negative staphylococci species, 17.8% streptococci and 7.1% Nocardia species. Less commonly recorded were Gram-negative bacteria (14%), with Pseudomonas aeruginosa (circa 10%) and Klebsiella pneumonia (4%) being the most common Gram-negative bacteria. In rare cases, fungi have also been reported. ICRS-related bacterial infections can be categorised into early or late onset. Early onset infection typically manifests within the first few weeks after implantation and is often associated with contamination during surgery, unhygienic practices, or inadequate sterilisation techniques. On the other hand, late-onset infection may develop months or even years after the initial procedures and may be associated with persistent bacterial colonisation, secondary infections, or prolonged use of prophylactic antibiotics. S aureus is encountered in both early and late-onset infections, while Nocardia species and K. pneumoniae have generally been reported to occur in late-onset infections. In addition, vision recovery from S. aureus infections tends to be poor compared to other bacterial infections. Conclusion: S. aureus is a predominant pathogen that often requires surgical intervention with poor outcomes. Early infections result from incision gaps and ring segment rubbing, while late infections are linked to prolonged antibiotic use. Further research is needed on novel antimicrobial ICRS to procure the vision. [ABSTRACT FROM AUTHOR]

Heterocyclic systems containing 2-(2-hydrazinyl) thiazole moieties were synthesized by heterocyclization of thiosemicarbazones with arylglyoxals and Meldrum's acid in ethanol and water 1:1 (v/v) under reflux conditions. The paper reports an efficient, facile, and environmentally friendly protocol via a novel one-pot three-component reaction to access a broad range of 2-(2-Hydrazinyl) thiazole derivatives. Products were isolated by plate chromatography and their structures were established from their spectroscopic data, then the antibacterial and antioxidant activity of synthesized 2-(2-hydrazinyl) thiazole derivatives were evaluated, and demonstrated encouraging antibacterial activity against Staphylococcus aureus as a gram positive bacteria and Escherichia coli as a gram negative bacteria. Furthermore, when representative products were assessed for radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH0), high antioxidant effects were observed, indicating their potential safety for use in pharmacological studies. [ABSTRACT FROM AUTHOR]

Between 2016 and 2019, the proportion of Escherichia coli bloodstream infection (BSI) with resistance to at least one antibiotic increased nationally. Public health interventions implemented in response to the COVID-19 pandemic changed population contact patterns and healthcare systems, with consequent effects on epidemiological trends of numerous pathogens. We investigated the impact of COVID-19 restrictions on epidemiological trends of E. coli BSI antimicrobial resistance (AMR) across South West England. We undertook a retrospective ecological analysis utilizing routine surveillance data of E. coli BSI cases reported to the UK Health Security Agency between 2016 and 2021. We analysed AMR trends for antimicrobial agents including amoxicillin–clavulanate, ciprofloxacin, piperacillin–tazobactam, gentamicin, third-generation cephalosporins and carbapenems before and after the implementation of COVID-19 restrictions (23 March 2020) using Bayesian segmented regression. We identified 19 055 cases. A total of 50.2% were male. Median age was 76 (interquartile range, 65–85 years). Piperacillin–tazobactam (–2.90% [95% highest density interval {HDI} –4.51%, –0.48%]) and ciprofloxacin (–2.40% [95% HDI –4.35%, 0.48%]) resistance demonstrated immediate step changes at the implementation of COVID-19 restrictions. Gentamicin (odds ratio [OR] 0.92 [95% HDI 0.76, 1.12]) and third-generation cephalosporins (OR 0.95 [95% HDI 0.80, 1.14]) exhibited decreasing annual resistance trends after the implementation of COVID-19 restrictions, with moderate evidence for a lower OR after restrictions as compared to the period before (gentamicin Bayes Factor = 5.10, third-generation cephalosporins Bayes Factor = 6.67). COVID-19 restrictions led to abrupt and longer term changes to E.coli BSI AMR. The immediate effects suggest altered transmission, whereas changes to resistant E. coli reservoirs may explain trend effects. [ABSTRACT FROM AUTHOR]

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It is essential to refrain from unnecessary isolation measures indicated for patients identified with multidrug-resistant Gram-negative bacteria (MDR-GNB). To evaluate whether a pro-active follow-up strategy to discontinue isolation measures of patients identified with MDR-GNB (without carbapenemase production) resulted in reduced isolation days during hospitalization, compared to passive follow-up. A comparison was made between active and passive follow-up strategies over a two-year period after first MDR-GNB identification. Patients could be declared negative after two consecutive negative screening cultures. Active follow-up patients received a questionnaire for screening cultures within six months of MDR-GNB identification. Of the 2208 patients included, 1424 patients (64.5%) underwent passive follow-up and 784 patients (35.5%) underwent active follow-up. A significantly higher proportion of active follow-up patients who had sufficient (at least two) screening cultures were declared MDR-GNB negative compared to those with passive follow-up; 66.9% vs 20.6% (P < 0.001) for adult patients and 76.0% vs 17.1% (P < 0.001) for paediatric patients. A comparison between active follow-up patients with sufficient versus those with active follow-up but insufficient cultures revealed a reduction of isolation days for paediatric patients (median 10.6 vs 1.6 days; P = 0.031). Though this difference was not statistically significant for adults (median 5.3 vs 4.2 isolation days), there was a valuable decrease in the number of isolation days for both adult and paediatric patients under active follow-up with sufficient (≥2) cultures, indicating clinical relevance. We recommend an active follow-up strategy for patients identified with an MDR-GNB, to prevent further unneeded infection prevention measures. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant (CR) Gram-negative bacteria have become a significant public health problem in the last decade. In recent years, the prevalence of CR bacteria has increased. The resistance to carbapenems could result from different mechanisms such as loss of porin, penicillin-binding protein alteration, carbapenemase, efflux pump, and biofilm community. Additionally, genetic variations like insertion, deletion, mutation, and post-transcriptional modification of corresponding coding genes could decrease the susceptibility of bacteria to carbapenems. In this regard, scientists are looking for new approaches to inhibit CR bacteria. Using bacteriophages, natural products, nanoparticles, disulfiram, N-acetylcysteine, and antimicrobial peptides showed promising inhibitory effects against CR bacteria. Additionally, the mentioned compounds could destroy the biofilm community of CR bacteria. Using them in combination with conventional antibiotics increases the efficacy of antibiotics, decreases their dosage and toxicity, and resensitizes CR bacteria to antibiotics. Therefore, in the present review article, we have discussed different aspects of non-antibiotic approaches for managing and inhibiting the CR bacteria and various methods and procedures used as an alternative for carbapenems against these bacteria. [ABSTRACT FROM AUTHOR]

Infections caused by multidrug-resistant (MDR) bacteria are typically associated with high morbidity and mortality, especially in vulnerable individuals such as patients with prolonged hospitalizations, immunocompromised individuals, and the elderly. This study aimed to provide post-marketing surveillance results concerning the prevalence of antibiotic resistance against Gram-negative bacteria through the collaboration of a multidisciplinary team. Patients involved have been treated with new antibacterial drugs, in particular ceftazidime/avibactam (C/A), meropenem/vaborbactam (M/V), cefiderocol, and ceftolozane/tazobactam (C/T). The most resistant bacterial species were Klebsiella spp., Pseudomonas aeruginosa, and Acinetobacter baumannii. Italian Drug Agency (AIFA) monitoring records for inpatients have been collected and analyzed, assessing the characteristics of the patients involved. Adverse drug reactions (ADRs) and drugs involved have been reported using a descriptive analytical approach. All data have been collected retrospectively from patient's medical records and entered into an electronic case report form (CRF). Among the 104 treated patients, Klebsiella spp. accounted for 50.1% of infections, Pseudomonas aeruginosa for 32.7%, Acinetobacter baumannii for 3%, and other bacterial species for 1.92% configuring polymicrobial infections. Regarding treatment outcomes, healing was achieved in 61 (58.6%) patients, 23 (22.1%) patients died, 8 (7.7%) patients discontinued empirical therapy, and 3 (2.9%) patients were lost to follow-up. Despite the introduction of new antibacterial drugs active against Gram-negative bacteria is improving the clinical scenario, it is crucial that the use of new antibacterial drugs be implemented by appropriate antimicrobial stewardship, surveillance programs, and monitoring efforts to prevent further spread of resistance. This study showed that the new antibiotics have good efficacy against MDR bacteria and cause negligible side effects. [ABSTRACT FROM AUTHOR]

Background: Proteus mirabilis is a Gram-negative, rod-shaped bacterium widely found in natural environments. It is known for causing a range of severe illnesses in mammals, particularly urinary tract infections (UTIs). This study evaluates the therapeutic efficacy of phage P2-71 against Proteus mirabilis in vivo and in vitro environments. Methods: The in vitro therapeutic potential of bacteriophage P2-71 was assessed through the ability of phage to kill Proteus mirabilis by using a plate counting assay, and biofilm inhibition and biofilm lysis assays using a microtitre plate method. Additionally, an in vivo UTI model in C57BL/6Jmice was developed via urethral inoculation of the bacterium. Phage therapy was administered through urethral injection over a period of 5 days. Therapeutic outcomes were measured by analyzing bacterial load, phage titer, inflammatory markers, and histopathological changes in the urine, urogenital tissues, and spleen. Results: In vitro, bacteriophage P2-71 achieved significant reductions in P. mirabilis concentrations, with log reductions of 1.537 and 0.7009 CFU/mL in laboratory and urine environments, respectively (p < 0.001). The phage also decreased biofilm formation by 34-49% and lysed 15-25% of mature biofilms at various multiplicities of infection (MOIs) (p < 0.001). In vivo, phage treatment significantly lowered bacterial concentrations in the urine on Days 1 and 3 (p < 0.0001), achieving a maximum reduction of 4.602 log10 CFU/mL; however, its effectiveness diminished by Day 5 (p > 0.05). Concurrently, phage titers decreased over time. Importantly, phage treatment notably reduced bacterial load in the bladder, kidneys, and spleen (p < 0.001). Inflammatory markers such as IL-6, IL-1β, and TNF-α were significantly lower in the treatment group, especially in the bladder (p < 0.0001), indicating an effective reduction in inflammation. Histopathological analysis showed significant mitigation of tissue damage. Conclusion: The results demonstrated that bacteriophage P2-71 is a promising alternative therapy for UTIs caused by MDR Proteus mirabilis. This bacteriophage therapy offers a viable strategy for managing infections where traditional antimicrobials fail, highlighting its potential in clinical applications. [ABSTRACT FROM AUTHOR]

The study successfully produced a hybrid nanocomposite of silver nanoparticles embedded with end-of-life battery-derived sheets-like nitrogen and sulfur-doped reduced-graphene oxide (AgNPs@NSG), which was utilized to remove methylene blue (MB) and paracetamol (PC) from aqueous solutions. The AgNPs@NSG nanocomposite was analyzed using various techniques. Several conditions, including pH value, adsorbent dose, initial concentration, and contact time, were studied to improve the removal efficiency of MB and PC. The pseudo-second-order model was the best fit for both MB and PC adsorption kinetics. The Langmuir model effectively described the experimental data for the adsorption isotherm, with maximum adsorption capacities of 61.72 and 52.6 mg/g for MB and PC, respectively, at room temperature. Additionally, the AgNPs@NSG nanocomposite demonstrated promising antibacterial activity against Gram-positive and Gram-negative bacteria. The nanocomposite showed inhibition zone diameters of 12.00 mm for Bacillus subtilis, 10.33 mm for Staphylococcus aureus, 9.67 mm for Streptococcus mutans, 10.00 mm for Escherichia coli, 11.33 mm for Proteus vulgaris, 9.67 mm for Serratia marcescens, and 10.67 mm for Vibrio parahaemolyticus. These results indicate the potential of AgNPs@NSG for reducing microorganism infections, especially in wastewater treatment. Overall, this study presents a simple and cost-effective process for producing an efficient material to remove harmful pollutants from wastewater. It also demonstrates its additional antimicrobial properties, highlighting its potential for versatile applications in environmental cleanup and infection control. [ABSTRACT FROM AUTHOR]

Arthropod-borne rickettsioses comprise a wide variety of subtypes that are endemic in Cambodia, but there remains very little data on the geographic distribution of the pathogens or their vectors. Surveys were conducted in Koh Kong and Preah Sihanouk Provinces between September 2017 and June 2018 to collect ectoparasites from peridomestic animals and the environment using dragging and flagging methods. Collected ectoparasites were sorted and identified morphologically, then pooled by species, host, and location for molecular detection using Rickettsia genus- and species-specific qPCR and/or multilocus sequence typing (MLST) assays. A total of 14,254 ectoparasites were collected including seven new locality records. Rickettsia species were detected in 35.5% (174/505) of the pools screened representing 3,149 randomly selected ectoparasites from the total collected. Rickettsia asembonensis was detected in 89.6% (147/164) of Rickettsia-positive flea pools and 3.6% (6/164) of the flea pools were positive for both R. asembonensis and Rickettsia felis. Candidatus Rickettsia senegalensis from Ctenocephalides orientis fleas and Rickettsia sp. close to Rickettsia japonica and Rickettsia heilongjiangensis from Haemaphysalis ticks were identified by MLST. This appears to be the first report of these new ectoparasite records and rickettsial species in southern Cambodia, suggesting a potential health risk to military and civilians in this region. Author summary: Rickettsiae are Gram-negative bacteria that cause acute undifferentiated febrile illness in humans. These pathogens are associated with arthropods and primarily transmitted by ectoparasites such as ticks, fleas, and mites. In Cambodia, rickettsial diseases have been documented in local patients, travelers and military personnel. However, the lack of entomological studies and awareness of these diseases hindered our comprehensive understanding of these pathogens and their arthropod vectors. Our manuscript provides a description of ectoparasite diversity and sheds light on their potential role in rickettsial disease transmission. Through molecular techniques, we uncover the prevalence and diversity of Rickettsia species in ectoparasites collected from various animal hosts in Koh Kong and Preah Sihanouk province. Rickettsia asembonensis, Rickettsia felis, and Candidatus Rickettsia senegalensis were all identified from Ctenocephalides orientis fleas, while Rickettsia species closely related to Rickettsia japonica, Rickettsia heilongjiangensis, and Rickettsia raoultii were found from Haemaphysalis ticks. Additionally, Rickettsia were also detected in Heterodoxus spiniger lice and Laelapidae mites, although we were unable to characterize the species. Insights into this pathogen-vector-host interface will better inform healthcare professionals, leading to more accurate diagnoses and increased awareness for better management of these diseases. [ABSTRACT FROM AUTHOR]

The rapid emergence and spread of multidrug-resistant bacterial pathogens require the development of antibacterial agents that are robustly effective while inducing no toxicity or resistance development. In this context, we designed and synthesized amphiphilic dendrimers as antibacterial candidates. We report the promising potent antibacterial activity shown by the amphiphilic dendrimer AD1b, composed of a long hydrophobic alkyl chain and a tertiary amine-terminated poly(amidoamine) dendron, against a panel of Gram-negative bacteria, including multidrug-resistant Escherichia coli and Acinetobacter baumannii. AD1b exhibited effective activity against drug-resistant bacterial infections in vivo. Mechanistic studies revealed that AD1b targeted the membrane phospholipids phosphatidylglycerol (PG) and cardiolipin (CL), leading to the disruption of the bacterial membrane and proton motive force, metabolic disturbance, leakage of cellular components, and, ultimately, cell death. Together, AD1b that specifically interacts with PG/CL in bacterial membranes supports the use of small amphiphilic dendrimers as a promising strategy to target drug-resistant bacterial pathogens and addresses the global antibiotic crisis. [ABSTRACT FROM AUTHOR]

Healthcare-associated infections (HAIs) caused by multidrug-resistant organisms (MDROs) represent a global threat to human health and well-being. Because transmission of MDROs to patients often occurs via transiently contaminated hands of healthcare personnel (HCP), hand hygiene is considered the most important measure for preventing HAIs. Environmental surfaces contaminated with MDROs from colonized or infected patients represent an important source of HCP hand contamination and contribute to transmission of pathogens. Accordingly, facilities are encouraged to adopt and implement recommendations included in the World Health Organization hand hygiene guidelines and those from the Society for Healthcare Epidemiology of America/Infectious Diseases Society of America/Association for Professionals in Infection Control and Epidemiology. Alcohol-based hand rubs are efficacious against MDROs with the exception of Clostridiodes difficile, for which soap and water handwashing is indicated. Monitoring hand hygiene adherence and providing HCP with feedback are of paramount importance. Environmental hygiene measures to curtail MDROs include disinfecting high-touch surfaces in rooms of patients with C. difficile infection daily with a sporicidal agent such as sodium hypochlorite. Some experts recommend also using a sporicidal agent in rooms of patients colonized with C. difficile, and for patients with multidrug-resistant Gram-negative bacteria. Sodium hypochlorite, hydrogen peroxide, or peracetic acid solutions are often used for daily and/or terminal disinfection of rooms housing patients with Candida auris or other MDROs. Products containing only a quaternary ammonium agent are not as effective as other agents against C. auris. Portable medical equipment should be cleaned and disinfected between use on different patients. Detergents are not recommended for cleaning high-touch surfaces in MDRO patient rooms, unless their use is followed by using a disinfectant. Facilities should consider using a disinfectant instead of detergents for terminal cleaning of floors in MDRO patient rooms. Education and training of environmental services employees is essential in assuring effective disinfection practices. Monitoring disinfection practices and providing personnel with performance feedback using fluorescent markers, adenosine triphosphate assays, or less commonly cultures of surfaces, can help reduce MDRO transmission. No-touch disinfection methods such as electrostatic spraying, hydrogen peroxide vapor, or ultraviolet light devices should be considered for terminal disinfection of MDRO patient rooms. Bundles with additional measures are usually necessary to reduce MDRO transmission. [ABSTRACT FROM AUTHOR]

Background: Colistin, administered as intravenous colistimethate (CMS), is still used in the critical care setting and current guidelines recommend high dosage CMS in patients undergoing continuous renal replacement therapy (CRRT). Due to the paucity of real-life data, we aimed to describe colistin pharmacokinetic/pharmacodynamic (PK/PD) profile in a cohort of critically ill patients with infections due to carbapenem-resistant (CR) bacteria undergoing CRRT. Results: All consecutive patients admitted to three Intensive Care Units (ICUs) of a large metropolitan University Hospital, treated with colistin for at least 48 h at the dosage of 6.75 MUI q12, after 9 MIU loading dose, and undergoing CRRT were included. After the seventh dose, patients underwent blood serial sampling during a time frame of 24 h. We included 20 patients, who had CR-Acinetobacter baumannii ventilator-associated pneumonia and were characterized by a median SAPS II and SOFA score of 41 [34.5–59.3] and 9 [6.7–11], respectively. Fifteen patients died during ICU stay and six recovered renal function. Median peak and trough colistin concentrations were 16.6 mcg/mL [14.8–20.6] and 3.9 mcg/mL [3.3–4.4], respectively. Median area under the time–concentration curve (AUC0 − 24) and average steady-state concentration (Css, avg) were 193.9 mcg h/mL [170.6–208.6] and 8.07 mcg/mL [7.1–8.7]. Probability of target attainment of colistin pharmacodynamics according to the fAUC0 − 24/MIC target ≥ 12 was 100% for MIC ≤ 2 mcg/mL and 85% for MIC = 4 mcg/ML, although exceeding the toxicity limit of Css, avg 3–4 mcg/mL. Conclusions: In critically ill patients with CR infections undergoing CRRT, recommended CMS dosage resulted in colistin plasmatic levels above bacterial MIC90, but exceeding the safety Css, avg. limit. Trial registration: This trial was registered in ClinicalTrials.gov on 23/07/2021 with the ID NCT04995133 (https//clinicaltrials.gov/study/NCT04995133). [ABSTRACT FROM AUTHOR]

Background: Acinetobacter baumannii continued to be an important Gram-negative pathogen of concern in the clinical context. The resistance of this pathogen to carbapenems due to the production of carbapenemases is considered a global threat. Despite the efforts to track carbapenemase synthesis among A. baumannii in the Philippines, local data on its molecular features are very scarce. This study aims to characterize A. baumannii clinical isolates from a Philippine tertiary hospital through genotyping of the pathogen's carbapenemase genes. Methods: Antibiotic susceptibility profiling, phenotypic testing of carbapenemase production, and polymerase chain reaction assays to detect the different classes of carbapenemase genes (class A blaKPC, class B blaNDM, blaIMP, blaVIM, and class D blaOXA-23-like, blaOXA-24/40-like, blaOXA-48-like, blaOXA-51-like, ISAba1-blaOXA-51-like, blaOXA-58-like) were performed in all collected A. baumannii, both carbapenem resistant and susceptible (n = 52). Results: Results showed that the majority of the carbapenem-resistant strains phenotypically produced carbapenemases (up to 84% in carbapenem inactivation methods) and possessed the ISAba1-blaOXA-51-like gene complex (80%). Meanwhile, both carbapenem-resistant and carbapenem-susceptible isolates possessed multi-class carbapenemase genes including blaNDM (1.9%), blaVIM (3.9%), blaOXA-24/40-like (5.8%), blaOXA-58-like (5.8%), blaKPC (11.5%), and blaOXA-23-like (94.2%), which coexist with each other in some strains (17.3%). In terms of the intrinsic blaOXA-51-like (oxaAb) genes, 23 unique alleles were reported (blaOXA-1058 to blaOXA-1080), the majority of which are closely related to blaOXA-66. Isolates possessing these alleles showed varying carbapenem resistance profiles. Conclusions: In summary, this study highlighted the importance of molecular genotyping in the characterization of A. baumannii by revealing the carbapenemase profiles of the pathogen (which may not be captured accurately in phenotypic tests), in identifying potent carriers of transferrable carbapenemase genes (which may not be expressed straightforwardly in antimicrobial susceptibility testing), and in monitoring unique pathogen epidemiology in the local clinical setting. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is a worldwide Gram-negative bacterium with a high resistance rate, responsible for a broad spectrum of hospital-acquired infections. A computational chemogenomics framework was applied to investigate the repurposing of approved drugs to target A. baumannii. This comprehensive approach involved compiling and preparing proteomic data, identifying homologous proteins in drug-target databases, evaluating the evolutionary conservation of targets, and conducting molecular docking studies and in vitro assays. Seven drugs were selected for experimental assays. Among them, tavaborole exhibited the most promising antimicrobial activity with a minimum inhibitory concentration (MIC) value of 2 μg/ml, potent activity against several clinically relevant strains, and robust efficacy against biofilms from multidrug-resistant strains at a concentration of 16 μg/ml. Molecular docking studies elucidated the binding modes of tavaborole in the editing and active domains of leucyl-tRNA synthetase, providing insights into its structural basis for antimicrobial activity. Tavaborole shows promise as an antimicrobial agent for combating A. baumannii infections and warrants further investigation in preclinical studies. [ABSTRACT FROM AUTHOR]

Ciprofloxacin has been used to replace tryptophan at positions 3 and 6 in the antimicrobial peptide (AMP) Bac8c. Bac8c(Cip3,6) showed comparable antimicrobial activity but increased selectivity toward some Gram-negative bacteria with MIC values of ≤6.25 μM. Bac8c(Cip3,6) was also non-cytotoxic to cultured HepG2 cells at antimicrobial concentrations, with a CC50 >300 μM. [ABSTRACT FROM AUTHOR]

Background: Given the limited treatment options available for oral lichen planus (OLP), a study was undertaken to obtain preliminary information on the therapeutic efficacy of tinidazole mouth rinse in patients with OLP. Methods: A prospective, open-label pilot study was conducted to assess the efficacy of thrice-daily tinidazole mouth rinse for one week in OLP patients (n = 27). Reticulation/erythema/ulceration (REU) scores and visual analog scale (VAS) scores were used to measure lesions at baseline and after one week of treatment. Mucosal samples were collected, and the abundance of Fusobacterium nucleatum was quantified using RT-PCR. Statistical analysis using t-test, Wilcoxon signed rank test and Pearson correlation test. Results: After treatment, VAS scores significantly decreased in both reticular (P = 0.03) and erosive OLP patients (P = 0.003). However, REU scores significantly decreased only in erosive OLP patients (P = 0.002). The relative abundance of Fusobacterium nucleatum on the damaged mucosa surface significantly decreased in all OLP patients (P = 0.01). In erosive OLP patients, the triamcinolone group showed a significantly greater improvement in VAS scores compared to the tinidazole group (P = 0.01). However, there was no statistically significant correlation between the relative abundance of Fusobacterium nucleatum and REU scores in OLP patients (r = 0.0754, P = 0.61). Conclusion: Tinidazole mouth rinse showed potential in reducing disease severity in OLP patients and was well-tolerated, suggesting its viability as a local therapeutic option. However, randomized controlled studies are warranted to confirm these preliminary findings. [ABSTRACT FROM AUTHOR]

Bacterial biofilms have been implicated in several chronic infections. After initial attachment, a critical first step in biofilm formation is a cell inducing a surface-sensing response. In the Gram-negative opportunistic pathogen Pseudomonas aeruginosa, two second messengers, cyclic diguanylate monophosphate (c-di-GMP) and cyclic adenosine monophosphate (cAMP), are produced by different surface-sensing mechanisms. However, given the disparate cellular behaviors regulated by these second messengers, how newly attached cells coordinate these pathways remains unclear. Some of the uncertainty relates to studies using different strains, experimental systems, and usually focusing on a single second messenger. In this study, we developed a tricolor reporter system to simultaneously gauge c-di-GMP and cAMP levels in single cells. Using PAO1, we show that c-di-GMP and cAMP are selectively activated in two commonly used experimental systems to study surface sensing. By further examining the conditions that differentiate a c-di-GMP or cAMP response, we demonstrate that an agarose-air interface activates cAMP signaling through type IV pili and the Pil-Chp system. However, a liquid-agarose interface favors the activation of c-di-GMP signaling. This response is dependent on flagellar motility and correlated with higher swimming speed. Collectively, this work indicates that c-di-GMP and cAMP signaling responses are dependent on the surface context. [ABSTRACT FROM AUTHOR]

Purpose: The prevalence of biliary tract diseases, which are common gastrointestinal disorders, is steadily rising. If it progresses to sepsis or septic shock, it can endanger the patient's life. Therefore, it is crucial to promptly diagnose bacterial infection in individuals suffering from biliary diseases and comprehend the risk factors associated with infection. The objective of this study was to examine the types of bacteria present in the bile of patients with biliary tract diseases, assess any alterations in their susceptibility to antimicrobial agents, and identify the risk factors contributing to the development of infection in these patients. Patients and methods: From June 2019 to November 2022, 317 patients of biliary tract diseases with positive bile culture were included in this hospital-based descriptive analysis. The hospital's computerized medical records were used to collect data on demographic information (including gender, age, and occupation), laboratory, and clinical findings, physical examination results, comorbidities, basic diseases, treatment history, complications, and in-hospital outcomes. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) principles. Results: Of the 317 patients with positive biliary tract diseases, 247 had benign diseases and 70 had malignant diseases. Patients with benign disease experienced a higher prevalence of statistically significant symptoms such as abdominal pain (81.4% vs. 57.1%, P = 0.000), nausea (31.2% vs. 14.3%, P = 0.005), vomiting (30.0% vs. 12.9%, P = 0.004), and chills (10.9% vs. 2.9%, P = 0.039), while jaundice (12.6% vs. 37.1%, P = 0.000) was more common in patients with malignant disease. At the species level, Escherichia coli (105; 40.5%), Klebsiella pneumoniae (41; 15.8%), and Pseudomonas aeruginosa (30; 11.6%) were the most commonly found Gram-negative bacterial strains in biliary tract infection. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were most susceptible to tigecycline, ertapenem and ceftazidime/avibactam, respectively. Conclusion: Gram-negative bacteria are the most commonly isolated biliary bacteria. Clinical doctors should pay attention to patients with malignant diseases with low hemoglobin, high total bilirubin and high alkaline phosphatase. Carbapenems, tigecycline, and minocycline are the recommended antibiotics for Enterobacteriaceae. In recent years, the proportion of enterococcus has gradually increased, and clinical attention should be paid to enterococcus infection. Linezolid and vancomycin were recommended for the treatment of Enterococci infections. Overall, this work can provide reference for clinical diagnosis, treatment and effective interventions. [ABSTRACT FROM AUTHOR]

Even though an astonishing variety of spirooxindole derivatives has been synthesized until now, the look for rapid, highly efficacious, environmental‐friendly and more skilful methods is yet an ongoing challenge. Here, we present a microwave‐assisted synthetic approach for the one‐pot synthesis of spirooxindole‐pyrimidine and spiro‐chromeno indoline‐trione derivatives in water using graphite oxide (GO) as a charismatic heterogeneous metal‐free carbocatalyst.Microwave‐assisted synthesis reduces the reaction times from hours (conventional heating) to minutes. The use of a heterogeneous catalyst allows for efficient recovery and reusability up to eight cycles without losing much of its effectiveness, thereby enhancing sustainability. This method offers high product yields of diverse substrates with low catalyst loading and simple work‐up and catalyst handling. In addition, the antimicrobial activities for some randomly taken compounds have also been studied against gram positive bacteria Staphylococcos aureus (MTCC96) and gram negative bacteria Escherichia coli(MTCC730). [ABSTRACT FROM AUTHOR]

An efficient stereoselective synthesis of tetrahydro‐1H‐isobenzofuro[4,5‐c]chromene‐1,3(3aH)‐dione derivatives were achieved through a novel [4+2] cycloaddition reaction of 4‐styryl‐2H‐chromenes with cheaply available maleic anhydride. A series of new tetrahydro‐1H‐isobenzofuro[4,5‐c]chromene‐1,3(3aH)‐dione derivatives 21(a–p) were synthesized in good to excellent yield under mild reaction condition with no chromatographic purification. In this reaction, the generation of four new consecutive stereogenic centers were determined by single crystal X‐ray analysis. All the synthesized compounds were investigated further in silico and in vitro for antibacterial activities using two bacterial strain of DNA gyrase. Compounds 21 b and 21 j showed excellent docking score −9.3 kCal/mol and −8.6 kCal/mol with gram negative bacterial strain Escherichia coli (E. coli) with protein data bank (PDB ID) 3G7E. Out of all the tested molecules, 21 b and 21 j displayed good results with minimum inhibitory concentration 10 μg/ml, 10 μg/ml against the bacterial strain Escherichia coli(E. coli) and 10 μg/ml, 20 μg/ml against Staphylococcus aureus (S. aureus) respectively. [ABSTRACT FROM AUTHOR]