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Dictyostelium discoideum is a phagocytic amoeba continuously eating, killing, and digesting bacteria. Previous studies have detected in D. discoideum cell extracts a bacteriolytic activity effective against Klebsiella pneumoniae bacteria. In this study, we characterized bacteriolytic activities found in D. discoideum cell extracts against five different bacteria ( K. pneumoniae , Escherichia coli , Pseudomonas aeruginosa , Staphylococcus aureus , and Bacillus subtilis ). We first analyzed the bacteriolytic activity against these five bacteria in parallel over a range of pH values. We then measured the remaining bacteriolytic activity in D. discoideum kil1 and modA knockout mutants. We also performed partial fractionation of D. discoideum extracts and assessed activity against different bacteria. Together our results indicate that optimal bacteriolytic activity against different bacteria results from the action of different effectors. Proteomic analysis allowed us to propose a list of potential bacteriolytic effectors.IMPORTANCEMany antibacterial effectors have been characterized over the past decades, and their biological importance, mode of action, and specificity are often still under study. Here we characterized in vitro bacteriolytic activity in D. discoideum extracts against five species of Gram-negative and Gram-positive bacteria. Our results reveal that optimal lysis of different bacteria mobilizes different effectors. Proteomic analysis generated a list of potential bacteriolytic effectors. This work opens the way for future analysis of the role of individual effectors in living D. discoideum cells., Competing Interests: The authors declare no conflict of interest.

This study retrospectively reviewed the microbiological and clinical characteristics of patients diagnosed with bacteremia. Results from the first positive blood cultures were consecutively collected from July 2022 to June 2023 at a public secondary hospital, a university-affiliated tertiary hospital, and a university-affiliated secondary hospital in the Seoul metropolitan area. Antibiotic spectrum coverage (ASC) scores were calculated on the day the blood culture was performed (B0) and on two days after the blood culture results were reported (R+2). A total of 3,397 isolates were collected from 3,094 patients. Among these, 949 isolates obtained from 893 patients were classified as multidrug-resistant organisms (MDRO), including 170 imipenem-resistant gram-negative bacteria, 714 methicillin-resistant staphylococci, and 65 vancomycin-resistant enterococci. Interestingly, 13 and 42 gram-positive isolates were resistant to linezolid and quinupristin/dalfopristin, respectively. Moreover, 44 and 181 gram-negative isolates were resistant to amikacin and tigecycline, respectively. The proportion of ASC scores corresponding to broad or extremely broad-spectrum coverage was not significantly different between MDRO and non-MDRO groups at B0 (p = 0.0925). However, it increased in the MDRO group at R+2 (p <0.001). This study found that resistance to last-resort antimicrobials is emerging. Therefore, developing and incorporating molecular diagnostics using a wide range of resistance targets may facilitate rapid, tailored antimicrobial treatments., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yoo 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.)

The dynamic nature of bacterial lipid membranes significantly impacts the efficacy of antimicrobial therapies. However, traditional assay methods often fall short in replicating the complexity of these membranes, necessitating innovative approaches. Herein, we successfully fabricated model bacterially supported lipid bilayers (SLBs) that closely mimic the characteristics of Gram-positive bacteria using the solvent-assisted lipid bilayer (SALB) technique. By employing a quartz crystal microbalance with dissipation and fluorescence microscopy, we investigated the interactions between these bacterial mimetic membranes and long-chain unsaturated fatty acids. Specifically, linolenic acid (LNA) and linoleic acid (LLA) demonstrated interaction behaviors correlated with the critical micelle concentration (CMC) on Gram-positive membranes, resulting in membrane remodeling and removal at concentrations above their respective CMC values. In contrast, oleic acid (OA), while showing similar membrane remodeling patterns to LNA and LLA, exhibited membrane insertion and CMC-independent activity on the Gram-positive membranes. Particularly, LNA and LLA demonstrated bactericidal effects and promoted membrane permeability and ATP leakage in the bacterial membranes. OA, characterized by a CMC-independent activity profile, exhibited potent bactericidal effects due to its robust penetration into the SLBs, also enhancing membrane permeability and ATP leakage. These findings shed light on the intricate molecular mechanisms governing the interactions between long-chain unsaturated fatty acids and bacterial membranes. Importantly, this study underscores the potential of using biologically relevant model bacterial membrane systems to develop innovative strategies for combating bacterial infections and designing effective therapeutic agents.

Background: Alteration in the etiology of pediatric bloodstream infections (BSIs) and antimicrobial resistance (AMR) is not well known during the Coronavirus disease 2019 (COVID-19) pandemic. This study aimed to investigate the impact of the COVID-19 pandemic on pediatric BSIs and alteration in antimicrobial resistance phenotypes in Gram-positive bacteria., Methods: The frequency of BSIs among children under 18 years old was retrospectively recorded in a tertiary children's hospital in Tehran, Iran from February 2020 to December 2022. The status of COVID-19 infection using reverse transcription polymerase chain reaction, bacteremia/fungemia according to BACTEC 9120 Culture System results, characterization of bacteria using biochemical tests, and antimicrobial susceptibility patterns for Gram-positive bacterial isolates using disk diffusion method were determined. Statistical analysis was done to measure the correlation of COVID-19 infection with BSIs and AMR., Results: Out of 13,345 COVID-19 tests and 4,194 BACTEC blood culture requests, bacteremia/fungemia were confirmed in 10.37% (435/4,194) of the patients who requested both tests simultaneously. The COVID-19 infection was confirmed in 25.3% (110/435) of the patients with bacteremia/fungemia. The infection with characterized Gram-positive bacteria (GPB) and fungi was detected in 32.3% (140/433) and 8.31% (36/433) of the cases, respectively. Coagulase-negative Staphylococcus (CNS, 72, 16.62%), S. aureus (36, 8.3%), and Enterococcus spp. (22, 5%) were among the common isolates. Candida spp. and non-Candida yeasts were detected in 6.7% and 13.4% of the cases, respectively. A positive correlation was shown between the CNS bacteremia and COVID-19 infection (p-value = 0.019). Antibiotic susceptibility testing results showed the highest frequency of resistance to azithromycin among CNS, azithromycin and tetracycline among S. aureus and tetracycline among Enterococcus spp. Methicillin-resistance phenotype in the S. aureus (MRSA) and coagulase-negative Staphylococcus spp. (MR-CNS) was detected in 40% and 61.5% of the strains, respectively and the Enterococci were resistant to vancomycin in 33.3% of the isolates., Conclusion: A decline in the trend of BSIs by GPB and an increase in AMR was shown in children during the COVID-19 pandemic. Increasing antibiotic resistance is a concern; however, chloramphenicol, linezolid, and vancomycin remain active against common causes of GPB-BSIs., (© 2024. The Author(s).)

Intending to homogenize the biological activities of both quinoxaline and imidazole moieties, the proligand, 1-methyl-3-quinoxaline-imidazolium hexaflurophosphate (1.HPF 6 ), and [Ag(1) 2 ][PF 6 ], (2); [Au(1) 2 ][PF 6 ], (3); and [Au(1)Cl 3 ], (4) NHC complexes were synthesized. All the synthesized compounds were characterized by elemental analysis, NMR, and UV-Vis spectroscopy. Finally, single crystal X-ray structures revealed a linear geometry for complex 2 whereas a square planar geometry for complex 4. The formation of complex 3 was confirmed and supported by its MS spectra. The antibacterial activities of all the synthesized complexes were investigated against gram-positive bacteria and gram-negative bacteria. The Au(III)-NHC complex, 4 showed the highest antibacterial activity with extremely low MIC values against both the bacterial strains (0.24 μg mL -1 ). Monitoring of zeta potential supports the higher activity of complex 4 compared to 2 and 3. ROS production by complex 4 has also been measured in vitro in the CT26 cancer cell lines, which is directly responsible for targetting and killing the bacterial pathogens. Cell cytotoxicity assay using 293T cell lines has been performed to investigate the biocompatibility nature of complex 4. Also, an excellent hemocompatibility was assigned to it from its hemolytic studies, which provide valuable insights into the design of novel antibacterial agents., (© 2024 Wiley-VCH GmbH.)

The present study reports on the valorisation of starch waste biomass to produce dual-active cryogels and hydrogels able to adsorb water and deliver antimicrobial substances for fresh food packaging applications. Starch hydrogels were prepared by oxidation with sodium metaperiodate in water and mild conditions, while cryogels were obtained by freeze-drying process. To explore the role of starch composition on the final properties of materials, two starches differing in amylose/amylopectin ratio, were evaluated. The prepared materials were microstructurally and morphologically characterized by FTIR and NMR spectroscopy (1D, 2D, and DOSY experiments), and SEM microscopy. To provide the materials with active properties, they were loaded with antimicrobial molecules by absorption, or by crosslinking via Schiff-base reaction. All materials demonstrated high water absorption capacity and ability to deliver volatile molecules, including diacetyl and complex mixtures like mint essential oil. The release profiles of the adsorbed molecules were determined through quantitative NMR spectroscopy over time. The antibacterial activity was successfully demonstrated against Gram-positive bacterial strains for unloaded cryogels and hydrogels, and after loading with diacetyl and essential oil. The developed materials can be regarded as part of active pads for food packaging applications capable to control moisture inside the package and inhibit microbial contamination., 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.)

The paper reports new hydrogels based on quaternary ammonium salts of chitosan designed as biocidal products. The chitosan derivative was crosslinked with salicylaldehyde via reversible imine bonds and supramolecular self-assemble to give dynamic hydrogels which respond to environmental stimuli. The crosslinking mechanism was demonstrated by 1 H NMR and FTIR spectroscopy, and X-ray diffraction and polarized light microscopy. The hydrogel nature, self-healing and thixotropy were proved by rheological investigation and visual observation, and their morphology was assessed by scanning electron microscopy. The relevant properties for application as biocidal products, such as swelling, dissolution, bioadhesiveness, antimicrobial activity and ex-vivo hemocompatibility and in vivo local toxicity and biocompatibility on experimental mice were measured and analyzed in relationship with the imination degree and the influence of each component. It was found that the hydrogels are superabsorbent, have good adhesivity to skin and various surfaces and antimicrobial activity against relevant gram-positive and gram-negative bacteria, while being hemocompatible and biocompatible. Besides, the hydrogels are easily biodegraded in soil. All these properties recommend the studied hydrogels as ecofriendly biocidal agents for living tissues and surfaces, but also open the perspectives of their use as platform for in vivo applications in tissue engineering, wound healing, or drug delivery 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The question being posed by scientists around the world is how different chemical modifications of naturally occurring compounds will affect their antimicrobial properties. In the current study, sulfur derivatives of camphor containing a sulfur atom were tested to detect their antimicrobial and antibiofilm potentials. The new compounds were tested on eight Gram-positive strains ( S. aureus (3 isolates), S. epidermidis (4 isolates), and E. faecalis (1 isolate)) and eight Gram-negative strains ( E. coli (6 isolates), A. baumannii (1 isolate), and P. aeruginosa (1 isolate)). The ability of the strains to eradicate a biofilm was evaluated under standard stationary and flow-through conditions using the Bioflux system. Two synthesized compounds, namely rac -thiocamphor ( 1a ) and (S, S)-(+)-thiocamphor ( 2a ), exhibited an effect on the 24 h biofilm formed by the Gram-positive strains. Our results are an important contribution to the science of natural compounds and allow us to classify our sulfur derivatives of camphor as potential prophylactic agents in treating skin infections, antiseptics, and disinfectants. The Gram-negative strains were excluded from further stages of the tests due to their high activity (MIC ≥ 512 µg/mL). On the other hand, the compound with the strongest antimicrobial activity against the Gram-positive strains was 2a , as it led led to a reductions in cell viability of 17-52% (for MIC), 37-66% (for 2MIC), and 40-94% (for 4MIC). In addition, the experimental retention index of thiocamphor was calculated for the first time.

This study investigates the potential of antimicrobial peptides (AMPs) as alternatives to combat antibiotic resistance, with a focus on two AMPs containing unnatural amino acids (UAAs), E2-53R (16 AAs) and LE-54R (14 AAs). In both peptides, valine is replaced by norvaline (Nva), and tryptophan is replaced by 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic). Microbiological studies reveal their potent activity against both Gram-negative (G(-)) and Gram-positive (G(+)) bacteria without any toxicity to eukaryotic cells at test concentrations up to 32 μM. Circular dichroism (CD) spectroscopy indicates that these peptides maintain α-helical structures when interacting with G(-) and G(+) lipid model membranes (LMMs), a feature linked to their efficacy. X-ray diffuse scattering (XDS) demonstrates a softening of G(-), G(+) and eukaryotic (Euk33) LMMs and a nonmonotonic decrease in chain order as a potential determinant for bacterial membrane destabilization. Additionally, XDS finds a significant link between both peptides' interfacial location in G(-) and G(+) LMMs and their efficacy. Neutron reflectometry (NR) confirms the AMP locations determined using XDS. Lack of toxicity in eukaryotic cells may be related to their loss of α-helicity and their hydrocarbon location in Euk33 LMMs. Both AMPs with UAAs offer a novel strategy to wipe out antibiotic-resistant strains while maintaining human cells. These findings are compared with previously published data on E2-35, which consists of the natural amino acids arginine, tryptophan, and valine.

Antimicrobial peptides (AMPs) are short, usually cationic peptides with an amphiphilic structure, which allows them to easily bind and interact with the cellular membranes of viruses, bacteria, fungi, and other pathogens. Bacterial AMPs, or bacteriocins, can be produced from Gram-negative and Gram-positive bacteria via ribosomal synthesis to eliminate competing organisms. Bacterial AMPs are vital in addressing the increasing antibiotic resistance of various pathogens, potentially serving as an alternative to ineffective antibiotics. Bacteriocins have a narrow spectrum of action, making them highly specific antibacterial compounds that target particular bacterial pathogens. This review covers the two main groups of bacteriocins produced by Gram-negative and Gram-positive bacteria, their modes of action, classification, sources of positive effects they can play on the human body, and their limitations and future perspectives as an alternative to antibiotics.

Gram-negative bacteria (GNB) pose a major global public health challenge as they exhibit a remarkable level of resistance to antibiotics. One of the factors responsible for promoting resistance against a wide range of antibiotics is the outer membrane (OM) of Gram-negative bacteria. The OM acts as a barrier that prevents the entry of numerous antibiotics by reducing their influx (due to membrane impermeability) and enhancing their efflux (with the help of efflux pumps). Our study focuses on analyzing the effect of IMT-P8, a cell-penetrating peptide (CPP), to enhance the influx of various Gram-positive specific antibiotics in multi-drug resistant Gram-negative pathogens. In the mechanistic experiments, IMT-P8 permeabilizes the OM at the same concentrations at which it enhances the activity of various antibiotics against GNB. Cytoplasmic membrane permeabilization was also observed at these concentrations, indicating that IMT-P8 acts on both the outer and cytoplasmic membranes. IMT-P8 interferes with the intrinsic resistance mechanism of GNB and has the potential to make Gram-positive specific antibiotics effective against GNB. IMT-P8 extends the post-antibiotic effect and in combination with antibiotics shows anti-persister activity. The IMT-P8/fusidic acid combination is effective in eliminating intracellular pathogens. IMT-P8 with negligible toxicity displayed good efficacy in murine lung and thigh infection models. Based on these findings, IMT-P8 is a potential antibiotic adjuvant to treat Gram-negative bacterial infections that pose a health hazard., Competing Interests: The authors declare no conflict of interest.

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 R 2 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 IC 50 value of carotenoids was used to indicate the antioxidant activity. IC 50 value from the DPPH assay was 152.80 mg/100mL. An IC 50 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 IC 50 values demonstrate biosafety. Overall, this bioprocess for enhanced carotenoid production coupled with bioactivity profiling and low cytotoxicity support the application of M. luteus carotenoids., (© 2024. The Author(s).)

Four synthetic Schiff bases (PSB1 [(E)-2-(((4-aminopyridin-3-yl)imino)methyl)-4,6-dibromophenol], PSB2 [(E)-2-(((4-aminopyridin-3-yl)imino)methyl)-4,6-diiodophenol], PSB3 [(E)-2-(((4-aminopyridin-3-yl)imino)methyl)-4-iodophenol], and PSB4 [(E)-2-(((4-aminopyridin-3-yl)imino)methyl)-4-chloro-6-iodophenol]) were fully characterized. These compounds exhibit an intramolecular hydrogen bond between the hydroxyl group of the phenolic ring and the nitrogen of the azomethine group, contributing to their stability. Their antimicrobial activity was evaluated against various Gram-negative and Gram-positive bacteria, and it was found that the synthetic pyridine Schiff bases, as well as their precursors, showed no discernible antimicrobial effect on Gram-negative bacteria, including Salmonella Typhi (and mutant derivatives), Salmonella Typhimurium, Escherichia coli , and Morganella morganii . In contrast, a more pronounced biocidal effect against Gram-positive bacteria was found, including Bacillus subtilis , Streptococcus agalactiae , Streptococcus pyogenes , Enterococcus faecalis , Staphylococcus aureus , and Staphylococcus haemolyticus . Among the tested compounds, PSB1 and PSB2 were identified as the most effective against Gram-positive bacteria, with PSB2 showing the most potent biocidal effects. Although the presence of reactive oxygen species (ROS) was noted after treatment with PSB2, the primary mode of action for PSB2 does not appear to involve ROS generation. This conclusion is supported by the observation that antioxidant treatment with vitamin C only partially mitigated bacterial inhibition, indicating an alternative biocidal mechanism.

The focus of current advances in nanotechnology has shifted significantly towards environmentally conscious methods that use harmless ingredients and moderated reaction circumstances to promote equitable development. Zinc oxide nanoparticles (NPs) currently grabbed attention of multiple medical fields owing to their unique ability to safeguard against cellular damage and alleviate serious human diseases via processes related to metabolism. This work focused on the generation of ZnO NPs using the peel of Cucumis melo fruit. The NPs were then analyzed and characterized using UV-Vis spectroscopy. The results indicated that at a wavelength of 352 nm, it was proven that the biosynthesis of ZnO NPs had occurred. The XRD pattern indicated the presence of dense crystal structures. The field emission scanning electron microscope (FE-SEM) picture confirmed the existence of polygonal-shaped ZnO NPs. The findings indicate that the produced ZnO NPs possess tough antibacterial properties against Gram-positive and Gram-negative microorganisms. When the ZnO NPs were exposed to direct sunshine for 80 min, they showed an 89% dye breakdown efficiency. This research specifically focused on the decomposition of reactivity dyes, with methylene blue dye being used as the target dye. The work demonstrates that the biosynthesis of ZnO NPs has a crucial and versatile role in the biological and environmental sectors., (© 2024 John Wiley & Sons Ltd.)

Three series of thiazolidinedione (TZD) derivatives (5a-f, 7a-f, and 9a-f) were prepared efficiently. Afterward, the synthesized candidates' antibacterial efficacy against both gram-positive and gram-negative bacteria was assessed. Compounds 7c, 7d, and 7f had values comparable to that of ampicillin, a reference antibiotic, whereas compounds 5c, 5d, and 7e exhibited the greatest values (23.0±1.0, 27.7±0.6, and 20.0±1.0, respectively) against gram-positive bacteria (Staphylococcus aureus). The optimal structure of the produced molecules was determined by DFT computing. To assess the binding energy and elucidate the interaction between the potential candidates and different proteins, in silico docking is employed. ADMET analysis to assess the synthesized compounds' toxicity, metabolism, excretion, distribution, and absorption., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Starch-based biofilms are biodegradable, but their application is limited by lower mechanical strength and absence of antimicrobial properties. In this context, the present study attempted to unleash the potential of nanotechnology for synthesizing nano-starch (NS) and tannic acid-coated nano-starch (T-NS) for augmenting the tensile strength and antimicrobial properties of starch-based biofilms. Moreover, this study reports one of the first such attempts to improve the commercial viability of starch extracted from the corms of Amorphophallus paeoniifolius. In this study, NS and T-NS samples were first synthesized by the physical and chemical modification of the native starch (S) molecules. The NS and T-NS samples showed significantly smaller granule size, lower moisture content, and swelling power. Further, amendments with NS and T-NS samples (25 % and 50 %) to the native starch molecules were performed to obtain biofilm samples. The NSB (NS amended) and T-NSB (T-NS amended) biofilms showed comparatively higher tensile strength than SB films (100 % starch-based). The T-NSB showed greater antimicrobial activity against gram-positive and gram-negative bacteria. All the biofilms showed almost complete biodegradation in soil (in 10 days). Therefore, it can be concluded that additives like NS and T-NS can improve starch-based biofilms' mechanical strength and antimicrobial properties with considerable biodegradability., 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.)

With the emergence of drug-resistance, there is a need for novel anti-bacterials or to enhance the efficacy of existing drugs. In this study, Patuletin (PA), a flavanoid was loaded onto Gallic acid modified Zinc oxide nanoparticles (PA-GA-ZnO), and evaluated for antibacterial properties against Gram-positive (Bacillus cereus and Streptococcus pneumoniae) and Gram-negative (Samonella enterica and Escherichia coli) bacteria. Characterization of PA, GA-ZnO and PA-GA-ZnO' nanoparticles was accomplished utilizing fourier-transform infrared spectroscopy, efficiency of drug entrapment, polydispersity index, zeta potential, size, and surface morphology analysis through atomic force microscopy. Using bactericidal assays, the results revealed that ZnO conjugation displayed remarkable effects and enhanced Patuletin's effects against both Gram-positive and Gram-negative bacteria, with the minimum inhibitory concentration observed at micromolar concentrations. Cytopathogenicity assays exhibited that the drug-nanoconjugates reduced bacterial-mediated human cell death with minimal side effects to human cells. When tested alone, drug-nanoconjugates tested in this study showed limited toxic effects against human cells in vitro. These are promising findings, but future work is needed to understand the molecular mechanisms of effects of drug-nanoconjugates against bacterial pathogens, in addition to in vivo testing to determine their translational value. This study suggests that Patuletin-loaded nano-formulation (PA-GA-ZnO) may be implicated in a multi-target mechanism that affects both Gram-positive and Gram-negative pathogen cell structures, however this needs to be ascertained in future work., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Gram-positive bacteria are frequently resistant to empirical beta-lactams in febrile neutropenic patients with cancer. As microbiology and antibiotic susceptibility changes, we reevaluated the risk factors for resistant Gram-positive bacteremia in febrile neutropenic patients with cancer., Methods: Episodes of bacteremic febrile neutropenia in Seoul National University Hospital from July 2019 to June 2022 were reviewed. Resistant Gram-positive bacteria were defined as a pathogen susceptible only to glycopeptide or linezolid in vitro (e.g., methicillin-resistant staphylococci, penicillin-resistant viridans streptococci, and ampicillin-resistant enterococci). Episodes were compared to identify independent risk factors for resistant Gram-positive bacteremia., Results: Of 225 episodes, 78 (34.7%) involved resistant Gram-positive bacteremia. Multivariate analysis revealed that breakthrough bacteremia while being administered antibiotics (adjusted odds ratio [aOR], 6.794; 95% confidence interval [95% CI], 3.130-14.749; P < 0.001) and catheter-related infection (aOR 4.039, 95% CI 1.366-11.946; P = 0.012) were associated with resistant Gram-positive bacteremia. Chronic liver disease (aOR 0.231, 95% CI 0.059-0.905; P = 0.035) and hypotension at bacteremia (aOR 0.454, 95% CI 0.218-0.945; P = 0.035) were inversely associated with resistant Gram-positive bacteremia., Conclusions: Resistant Gram-positive bacteria should be considered in breakthrough bacteremia and catheter-related infection in febrile neutropenic patients with cancer., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (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.)

Abstract: Infection of wounds delays healing, increases treatment costs, and leads to major complications. Current methods to manage such infections include antibiotic ointments and antimicrobial wound dressings, both of which have significant drawbacks, including frequent reapplication and contribution to antimicrobial resistance. In this work, we developed wound dressings fabricated with a medical-grade polyurethane coating composed of natural plant secondary metabolites, cinnamaldehyde, and alpha-terpineol. Our wound dressings are easy to change and do not adhere to the wound bed. They kill gram-positive and -negative microbes in infected wounds due to the Food and Drug Administration-approved for human consumption components. The wound dressings were fabricated by dip coating. Antimicrobial efficacy was determined by quantifying the bacteria colonies after a 24 h of immersion. Wound healing and bacterial reduction were assessed in an in vivo full-thickness porcine burn model. Our antimicrobial wound dressings showed a > 5-log reduction (99.999%) of different gram-positive and gram-negative bacteria, while maintaining absorbency. In the in vivo porcine burn model, our wound dressings were superior to bacitracin in decreasing bacterial burden during daily changes, without interfering with wound healing. Additionally, the dressings had a significantly lower adhesion to the wound bed. Our antimicrobial wound dressings reduced the burden of clinically relevant bacteria more than commercial antimicrobial wound dressings. In an in vivo infected burn wound model, our coatings performed as well or better than bacitracin. We anticipate that our wound dressings would be useful for the treatment of various types of acute and chronic wounds., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

In this study, six compounds were obtained from a methanolic extract of air-dried leaves of Senna alata and one of them, a triterpenoid (secofriedelane) named as 7-(2-carboxyethyl)-3, 4b, 6a, 8, 10a, 12a-hexamethyl-8-vinyloctadecahydrochrysene-3-carboxylic acid ( 5 ) was isolated for the first time from this plant. Then, its chemical structure was detailed and characterised by FT-IR, 1 H and 13 C- NMR and ESI-MS. Besides, two chemical-modified derivatives of secofriedelane ( 5a , 5b ) were synthesised by methylation and allylation reactions, respectively, and their in vitro antibacterial activities were also evaluated. The results revealed that all the triterpenes showed, against gram-positive and -negative bacterial strains, good and moderate antibacterial activities with bactericidal effects that were enhanced by the methyl groups and altered with the allyl ones. Moreover, the molecular docking results of 5 , 5a and 5b in the DNA gyrase (2XCT) active site showed that triterpene 5 has a good score very close to reference (ciprofloxacin).

Schiff bases of existing antimicrobial drugs are an area, which is still to be comprehensively explored to improve drug efficiency against consistently resisting bacterial species. In this study, we have targeted a new and eco-friendly method of condensation reaction that allows the "green synthesis" as well as improved biological efficacy. The transition metal complexes of cefpodoxime with well-enhanced biological activities were synthesized. The condensation reaction product of cefpodoxime and vanillin was further reacted with suitable metal salts of [Mn (II), Cu (II), Fe (II), Zn (II), and Ni (II)] with 1:2 molar ratio (metal: ligand). The characterization of all the products were carried out by using UV-Visible, elemental analyzer, FTIR, 1 H-NMR, ICP-OES, and LC-MS. Electronic data obtained by UV-Visible proved the octahedral geometry of metal complexes. The biological activities Schiff base ligand and its transition metal complexes were tested by using in-vitro anti-bacterial analysis against various Gram-negative, as well as Gram-positive bacterial strains. Proteinase and protein denaturation inhibition assays were utilized to evaluate the products in-vitro anti-inflammatory activities. The in vitro antioxidant activity of the ligand and its complexes was evaluated by utilizing the 2,2-diphenyl-1-picrylhydrazyl (DPPH) in-vitro method. The final results proved metal complexes to be more effective against bacterial microorganisms as compared to respective parent drug as well as their free ligands. Patch Dock, a molecular docking tool, was used to dock complexes 1a-5e with the crystal structure of GlcN-6-P synthase (ID: 1MOQ). According to the docking results, complex 2b exhibited a highest score (8,882; ACE = -580.43 kcal/mol) that is well correlated with a high inhibition as compared to other complexes which corresponds to the antibacterial screening outcomes., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The novel donor-acceptor (D-A) type covalent organic frameworks TATF-COF and TATP-COF, with multiple fluorine groups as electron storage units, were successfully constructed to achieve efficient charge transfer and photocatalytic activity for antibacterial photocatalytic therapy. Fluorine, the most electronegative element, was utilized as an electron-withdrawing substituent for the acceptor, which could unite the donor unit together and efficiently improve the charge transfer from the donor to acceptor. The unique D-A structures of TATF-COF and TATP-COF ensure that they have narrow band gaps, strong photocurrent responses, long fluorescence lifetimes, and good capacity to generate reactive oxygen species (ROS) to realize good antibacterial activity. Meanwhile, the inclusion of multiple hydrophilic fluorine groups means that TATF-COF and TATP-COF are highly water dispersible, which is also beneficial in terms of promoting the generation of adequate quantities of ROS. Hence, in view of their excellent photoelectric properties and good water dispersibility, further investigations were performed, and excellent antibacterial activities in vitro against both gram-negative and gram-positive bacteria were demonstrated for TATF-COF and TATP-COF. In addition, we also showed that they can function as effective antibacterial dental materials., 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.)

Bryophyllum pinnatum is used to cure infections worldwide. Although the flavonoids of this plant are well known, it is still unknown how much of the plant's Ag and ZnO nanoparticles are beneficial. In the current research work, silver and zinc oxide nanoparticles were prepared using Bryophyllum pinnatum extract. The synthesized particles were characterized by UV-visible spectroscopy, SEM, EDS, XRD and FTIR. Synthesized particles were subjected to evaluation of their bactericidal and antifungal activity at various doses. Uv vis spectra at 400 nm corresponding to AgNPs confirmed their synthesis. Strong peaks in the EDS spectra of Ag and ZnO indicate the purity of the sample. The scanning electron microscopic images of ZnONPs showed a size of about 60 nm ± 3 nm, which demonstrated the presence of triangular-shaped ZnO nanoparticles. Green synthesized nanoparticles showed bactericidal activity against both Gram-positive (Micrococcus luteus, Staphylococcus aureus, Bacillus subtilis) and Gram-negative (Agrobacterium tumifaciens, Salmonella setubal, Enterobacter aerogenes) strains. AgNPs proved to be more effective against Gram-negative bacterial strains compared to Gram-positive owing to MIC values (10 ppm and 20 ppm respectively). Whereas, ZnONPs were found more effective against Gram-positive bacteria with lower MIC values (10 ppm) as compared to Gram-negative ones (20 ppm). Also, the synthesized nanoparticles exhibited moderate dose-dependent antifungal activity against tested fungal strains ranging from 10 to 70%. Cytotoxicity of nanoparticles was found significant using Brine shrimp's lethality assay with IC 50 values of 4.09 ppm for AgNPs, 13.72 ppm for ZnONPs, and 24.83 ppm for plant extract. Conclusively, Ag and ZnO nanoparticles were more effective than plant extract and AgNPs had higher activities than those of ZnONPs. Further research is warranted to explore the precise mechanism of action and the potential applications of these nanoparticles in the medical field., (© 2024. The Author(s).)

The World Health Organization has identified antibiotic resistance as one of the three greatest threats to human health. The need for antibiotics is a pressing matter that requires immediate attention. Here, computer-aided drug design is used to develop a structurally unique antibiotic family targeting holo-acyl carrier protein synthase (AcpS). AcpS is a highly conserved enzyme essential for bacterial survival that catalyzes the first step in lipid synthesis. To the best of our knowledge, there are no current antibiotics targeting AcpS making this drug development program of high interest. We synthesize a library of > 700 novel compounds targeting AcpS, from which 33 inhibit bacterial growth in vitro at ≤ 2 μg/mL. We demonstrate that compounds from this class have stand-alone activity against a broad spectrum of Gram-positive organisms and synergize with colistin to enable coverage of Gram-negative species. We demonstrate efficacy against clinically relevant multi-drug resistant strains in vitro and in animal models of infection in vivo including a difficult-to-treat ischemic infection exemplified by diabetic foot ulcer infections in humans. This antibiotic family could form the basis for several multi-drug-resistant antimicrobial programs., (© 2024. The Author(s).)

Background: The growing concern of antibiotic-resistant microbial strains worldwide has prompted the need for alternative methods to combat microbial resistance. Biofilm formation poses a significant challenge to antibiotic efficiency due to the difficulty of penetrating antibiotics through the sticky microbial aggregates. Drug repurposing is an innovative technique that aims to expand the use of non-antibiotic medications to address this issue. The primary objective of this study was to evaluate the antimicrobial properties of Diltiazem HCl, a 1,5-benzothiazepine Ca 2 + channel blocker commonly used as an antihypertensive agent, against four pathogenic bacteria and three pathogenic yeasts, as well as its antiviral activity against the Coxsackie B4 virus (CoxB4)., Methods: To assess the antifungal and antibacterial activities of Diltiazem HCl, the well diffusion method was employed, while crystal violet staining was used to determine the anti-biofilm activity. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay was utilized to evaluate the antiviral activity of Diltiazem HCl against the CoxB4 virus., Results: This study revealed that Diltiazem HCl exhibited noticeable antimicrobial properties against Gram-positive bacteria, demonstrating the highest inhibition of Staphylococcus epidermidis , followed by Staphylococcus aureus . It effectively reduced the formation of biofilms by 95.1% and 90.7% for S. epidermidis , and S. aureus , respectively. Additionally, the antiviral activity of Diltiazem HCl was found to be potent against the CoxB4 virus, with an IC 50 of 35.8 ± 0.54 μg mL -1 compared to the reference antiviral Acyclovir (IC 50 42.71 ± 0.43 μg mL -1 )., Conclusion: This study suggests that Diltiazem HCl, in addition to its antihypertensive effect, may also be a potential treatment option for infections caused by Gram-positive bacteria and the CoxB4 viruses, providing an additional off-target effect for Diltiazem HCl., Competing Interests: The authors declare that they have no competing interests., (© 2024 Alduaij et al.)

The global crisis of antimicrobial resistance (AMR) necessitates the development of broad-spectrum antibacterial drugs effective against multi-drug resistant (MDR) pathogens. BWC0977, a Novel Bacterial Topoisomerase Inhibitor (NBTI) selectively inhibits bacterial DNA replication via inhibition of DNA gyrase and topoisomerase IV. BWC0977 exhibited a minimum inhibitory concentration (MIC 90 ) of 0.03-2 µg/mL against a global panel of MDR Gram-negative bacteria including Enterobacterales and non-fermenters, Gram-positive bacteria, anaerobes and biothreat pathogens. BWC0977 retains activity against isolates resistant to fluoroquinolones (FQs), carbapenems and colistin and demonstrates efficacy against multiple pathogens in two rodent species with significantly higher drug levels in the epithelial lining fluid of infected lungs. In healthy volunteers, single-ascending doses of BWC0977 administered intravenously ( https://clinicaltrials.gov/study/NCT05088421 ) was found to be safe, well tolerated (primary endpoint) and achieved dose-proportional exposures (secondary endpoint) consistent with modelled data from preclinical studies. Here, we show that BWC0977 has the potential to treat a range of critical-care infections including MDR bacterial pneumonias., (© 2024. The Author(s).)

This study describes the discovery and characterization of raffinocyclicin, a novel plasmid-encoded circular bacteriocin, produced by the raw milk isolate Lactococcus raffinolactis APC 3967. This bacteriocin has a molecular mass of 6,092 Da and contains 61 amino acids with a three-amino acid leader peptide. It shows the highest identity to the circular bacteriocins bacicyclicin XIN-1 (42.62%), aureocyclicin 4185 (42.62%), and garvicin ML (41.53%). A broad inhibitory spectrum includes strains from Staphylococcus , Enterococcus , Streptococcus , Micrococcus , Lactobacillus , Leuconostoc, and Listeria , in addition to a pronounced inhibitory effect against Lactococcus and Clostridium . It displays low sensitivity to trypsin, most likely as a result of its circular nature. The raffinocyclicin gene cluster is composed of 10 genes: 6 core genes, genes encoding an accessory three-component ABC transporter ( rafCDE ), and a putative transcriptional regulator related to the MutR family. A lack of inhibitory activity in the cell-free supernatant combined with the pronounced activity of cell extracts suggests that the majority of raffinocyclicin is associated with the cell rather than being released to the extracellular environment. This is the first report of a bacteriocin produced by the L. raffinolactis species.IMPORTANCEThe present study aimed to characterize raffinocyclicin, a novel circular bacteriocin produced by the lactic acid bacteria Lactococcus raffinolactis APC 3967. Bacteriocins are generally cationic and hydrophobic peptides with antimicrobial activity, which present diverse biotechnological properties of interest for the food industry. Raffinocyclicin inhibits a wide range of bacteria, including foodborne pathogens, and is stable against different treatments which suggest its potential as a natural biopreservative. Whole-genome sequencing and the genetic analysis of the raffinocyclicin gene cluster showed that it is encoded by plasmid that could be used in the future to transfer the ability to produce the bacteriocin to other lactic acid bacteria for industrial applications. These results together highlight the potential of this novel antimicrobial as a biopreservative to be used by the food industry., Competing Interests: The authors declare no conflict of interest.

A novel class of pleuromutilin derivatives possessing 1,2,3-triazole as the linker connected to phenyl analogues were designed. The antibacterial properties of the prepared compounds were assessed in vitro against five strains (E. coli, S. aureus, S. epidermidis, and E. faecalis). Most of the tested compounds displayed potent antibacterial activities against gram-positive bacteria and 14-O-[2-(4-((2,4-dinitrophenoxy)-methyl-1H-1,2,3-triazol-1-yl) acetamide)-2-methylpropan-2-yl) thioacetyl]mutilin (7c) exerted antibacterial activities against S. aureus, MRSA and S. epidermidis with MIC values 0.0625 μg/mL, representing 64-fold, 4-fold and 8-fold higher than tiamulin respectively. Compound 6e, 7c and 8c were chosen to carry out killing kinetics, which exhibited concentration-dependent effect. Subsequently, molecular modeling was conducted to further explore the binding of compound 6e, 7a, 7c, 8c and tiamulin with 50S ribosomal subunit from deinococcus radiodurans. The investigation revealed that the main interactions between compound 7c and the ribosomal residues were three hydrogen bonds, π-π, and p-π conjugate effects. Additionally, the free binding energy and docking score of 7c with the ribosome demonstrated the lowest values of -11.90 kcal/mol and -7.97 kcal/mol, respectively, consistent with its superior antibacterial activities., 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.)

The direct-linked coumarin-benzimidazole hybrids, featuring aryl and n-butyl substituents at the N1-position of benzimidazole were synthesized through a Knoevenagel condensation reaction. This reaction involved the condensation of 1,2-diaminobenzene derivatives with coumarin-3-carboxylic acids in the presence of polyphosphoric acid (PPA) at 154 °C. The in vitro antibacterial potency of the hybrid molecules against different gram-positive and gram-negative bacterial strains led to the identification of the hybrids 6m and 6p with a MIC value of 6.25 μg/mL against a gram-negative bacterium, Klebsiella pneumonia ATCC 27736. Cell viability studies on THP-1 cells demonstrated that the compounds 6m and 6p were non-toxic at a concentration of 50 µM. Furthermore, in vivo efficacy studies using a murine neutropenic thigh infection model revealed that both compounds significantly reduced bacterial (Klebsiella pneumonia ATCC 27736) counts (more than 2 log) compared to the control group. Additionally, both compounds exhibited favorable physicochemical properties and drug-likeness characteristics. Consequently, these compounds hold promise as lead candidates for further development of effective antibacterial drugs., 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.)

Metal complexes have emerged as a promising source for novel classes of antibacterial agents to combat the rise of antimicrobial resistance around the world. In the exploration of the transition metal chemical space for novel metalloantibiotics, the rhenium tricarbonyl moiety has been identified as a promising scaffold. Here we have prepared eight novel rhenium bisquinoline tricarbonyl complexes and explored their antibacterial properties. Significant activity against both Gram-positive and Gram-negative bacteria was observed. However, all complexes also showed significant toxicity against human cells, putting into question the prospects of this specific rhenium compound class as metalloantibiotics. To better understand their biological effects, we conduct the first mode of action studies on rhenium bisquinoline complexes and show that they are able to form pores through bacterial membranes. Their straight-forward synthesis and tuneability suggests that further optimisation of this compound class could lead to compounds with enhanced bacterial specificity., (© 2024 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

Herein, we report the anti-malarial, anti-bacterial and anti-inflammatory activities of the N 2 O 2 donor tetradentate salen type ligand and its CoL, NiL, and CuL metal complexes. The synthesized compounds were characterized by various spectroscopic analytical methods. The in-vitro anti-malarial investigations revealed that the complex CuL exhibited equipotency with quinine drug having IC 50 value 0.25 μg/mL. The compound L showed significant inhibition of bacterial spp. viz. E. Coli, P. Aeruginosa, and S. Aureus (MIC=12.5-50 μg/mL), while the compound CoL (MIC=12.5 μg/mL) exhibited potency against gram-positive bacteria. In the in-vitro anti-inflammatory study, the compound CuL displayed moderate activity than other tested compounds. The compound CuL showed the highest anti-malarial docking score with enzyme pLDH at -8.12 Kcal/mol. The DFT study also gives authentication of higher antimalarial activity of CuL due to high dipole moment. None of the potent compounds was found cytotoxic towards vero cell lines., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

The diminishing effectiveness of existing aminoglycoside antibiotics (AGs) compels scientists to seek new approaches to enhance the sensitivity of current AGs. Despite ongoing efforts, currently available approaches remain restricted. Herein, a novel strategy involving the rational construction of an aggregation-induced-emission luminogen (AIEgen) is introduced to significantly enhance Gram-positive bacteria's susceptibility to AGs. The application of this approach involves the simple addition of AIEgens to bacteria followed by a 5 min light irradiation. Under light exposure, AIEgens efficiently generate reactive oxygen species (ROS), elevating intrabacterial ROS levels to a nonlethal threshold. Post treatment, the bacteria swiftly enter a hypersensitive state, resulting in a 21.9-fold, 15.5-fold, or 7.2-fold increase in susceptibility to three AGs: kanamycin, gentamycin, and neomycin, respectively. Remarkably, this approach is specific to AGs, and the induced hypersensitivity displays unparalleled longevity and heritability. Further in vivo studies confirm a 7.0-fold enhanced bactericidal ability of AGs against Gram-positive bacteria through this novel approach. This research not only broadens the potential applications of AIEgens but also introduces a novel avenue to bolster the effectiveness of AGs in combating bacterial infections., (© 2024 Wiley‐VCH GmbH.)

The brassicas have the potential to prevent chronic non-communicable diseases and it is proposed to evaluate the chemical composition, antioxidant and antimicrobial potential of broccoli, cabbage and extracts. The extracts were prepared and characterized and the antioxidant potential was evaluated against three radicals while the antimicrobial potential was analyzed using three techniques against four bacteria. The extracts have glucosinolates and phenolic compounds in their composition, and effectively inhibit the 2,2-diphenyl-1-picrylhydrazyl radical. The extracts of broccoli and cauliflower showed an inhibitory effect against hydroxyl radicals and nitric oxide. Disk diffusion showed that broccoli and cauliflower extract were active against three bacteria, while kale extract showed active halos for Gram-negative bacteria. Kale extract had an inhibitory effect Gram-positive bacteria, cauliflower extract inhibited the growth of Staphylococcus aureus. The cauliflower extract thus had a higher concentration of phenols, a strong antioxidant activity and promising results at a concentration of 100 mg/mL against S. aureus., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The quest for novel antibacterial agents is imperative in the face of escalating antibiotic resistance. Naturally occurring tetrahydro-β-carboline (THβC) alkaloids have been highlighted due to their significant biological derivatives. However, these structures have been little explored for antibacterial drugs development. In this study, a series of 1,2,3,4-THβC derivatives were synthesized and assessed for their antibacterial prowess against both gram-positive and gram-negative bacteria. The compounds exhibited moderate to good antibacterial activity, with some compounds showing superior efficacy against gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), to that of Gentamicin. Among these analogs, compound 3k emerged as a hit compound, demonstrating rapid bactericidal action and a significant post-antibacterial effect, with significant cytotoxicity towards human LO2 and HepG2 cells. In addition, compound 3k (10 mg/kg) showed comparable anti-MRSA efficacy to Ciprofloxacin (2 mg/kg) in a mouse model of abdominal infection. Overall, the present findings suggested that THβC derivatives based on the title compounds hold promising applications in the development of antibacterial drugs., 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.)

Phyllanthus emblica L. (syn. Emblica officinalis) fruits have been traditionally exploited to enhance the immune system and provide protection against bacterial and fungal diseases. The present study aimed to evaluate the synergistic interactions between chloramphenicol and several phenolic compounds found in P. emblica fruits against bacterial strains. The combination of P. emblica fruit extracts and its phenolic compounds demonstrated synergistic antibacterial activity when used in conjunction with chloramphenicol against both Gram-positive and Gram-negative bacteria. The combination of MIC GA with ½MIC Chl exhibited a significant increase in bioactivity, with a 333.33-fold enhancement against B. subtilis. Similarly, the combination of MIC GA with 2MIC Chl displayed a bioactivity enhancement of 16.02 folds against S. aureus. The co-administration of ½MIC Q and ½MIC Chl resulted in a significant 35.71-fold increase in bioactivity against P. aeruginosa. Similarly, the combination of MIC GA and ½MIC Chl exhibited a remarkable 166.66-fold enhancement in bioactivity against E. coli. The combinations of 2MIC FPE and ½MIC Chloramphenicol , as well as ½MIC GA and ½MIC Chl demonstrated the highest bioactivity enhancement of 17.85 folds for K. pneumoniae. This study claimed that the fruit extracts of P. emblica and its phenolic compounds could be utilized to augment the effectiveness of conventional antibiotics, which have acquired resistance to bacterial infections., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Antimicrobial susceptibility testing (AST) from blood culture (BC) may take several days, limiting the eventual impact on antimicrobial stewardship. Hence, rapid AST systems represent a valuable support in shorting the time-to-response. In this work, the Quantamatrix dRAST TM system (dRAST) was evaluated for rapid AST on 100 monomicrobial BCs (50 Gram-negatives and 50 Gram-positives), including several isolates with clinically relevant resistance mechanisms. AST results were provided in 6-hours, on average. Compared to Micronaut (Merlin) system based on broth microdilution, dRAST exhibited an overall categorical agreement of 92.5 %, essential agreement of 89.0 %, and mean bias of 15.9 %. Category overestimation (potentially leading to unnecessary high-dosage treatment or to exclude active agents) and category underestimation (potentially leading to underdosing or using ineffective agents) were observed in 4.3 % and 3.1 % of cases, respectively. Even though several issues were reported, results confirmed the potential contribution of dRAST to shorten the BCs clinical microbiology workflow and management., Competing Interests: Declaration of competing interest Outside the submitted work, AA reports consulting fees form Menarini; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events by Angelini, Menarini, Seegene, Ada, SD Biosensor, Qvella. Outside the submitted work, TG reports grants from Arrow, Coris, Merlin, Venatorx; Consulting fees for bioMérieux, Menarini, Thermofisher. Outside the submitted work, GMR reports grants or contracts to the laboratory from Ada, Alifax, Angelini, Arrow Diagnostics, Biomedical Service, bioMérieux, Cepheid, Hain Lifescience GmbH, Menarini, Meridian, MSD, Nordic Pharma, Qlinea, Quidel, Qvella, SD Biosensor, Seegene, Shionogi, Symcel; consulting fees from bioMérieux, MSD; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events by bioMérieux, Menarini, MSD, Pfizer, Shionogi, Relab. CC, MC and FM have none to declare. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: This study aims to investigate the changing epidemiology and antimicrobial susceptibility of bacteria isolated from cerebrospinal fluid (CSF) in the Shandong region., Methodology: We conducted a retrospective analysis of bacterial distribution and resistance patterns in CSF samples, utilizing data from the SPARSS network and analyzed with WHONET 5.6 software., Results: A total of 3968 pathogenic bacterial strains were isolated, consisting of 70.6% Gram-positive bacteria, 27.2% Gram-negative bacteria, and 0.2% fungi. The six most commonly detected bacteria were coagulase-negative staphylococcus, Acinetobacter baumannii, Klebsiella pneumoniae, Streptococcus pneumoniae, Escherichia coli, and staphylococcus aureus. Analysis revealed gender and seasonal variations in the distribution of CSF pathogens, with a higher incidence observed in males and during autumn compared to other seasons. The susceptibility profiles of these bacterial species varied significantly, with many exhibiting multidrug resistances. A. baumannii showed a high resistance rate to cephalosporins and carbapenems but was sensitive to tigecycline and polymyxins. For treating multidrug-resistant A. baumannii infections, polymyxin-based combinations with tigecycline or sulbactam are recommended for adults, while tigecycline combined with meropenem is suggested for children. Enterobacteriaceae species were generally sensitive to carbapenems, such as meropenem and other carbapenems that can penetrate the blood-brain barrier can be recommended. Linezolid and vancomycin are the first choice for treating common gram-positive bacterial infections., Conclusions: The high resistance rates observed among common CSF isolates and their varied distributions across different demographics highlight the necessity for customized treatment strategies., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Chunyan Zhang, Zheng Li, Mengyuan Wang, Shifu Wang.)

Background: Gram-positive bacteria residing in the nasopharynx can lead to severe illnesses in children, such as otitis media, pneumonia, and meningitis. Despite the potential threat, there is a lack of comprehensive data regarding the carriage rates of these bacteria among children in outpatient departments in the study area., Objective: This study aimed to assess the nasopharyngeal carriage, antimicrobial resistance patterns, and associated factors of Gram-positive bacteria among children attending the outpatient department at the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia., Methods: A hospital-based cross-sectional study was conducted from May 1, 2023, to August 30, 2023. A total of 424 nasopharyngeal swab samples were collected using sterile nasopharyngeal swabs, inoculated on Blood Agar and Mannitol Salt Agar plates, and identified through colony morphology, Gram stain, and biochemical tests. Antimicrobial susceptibility of the identified bacterial isolates was determined employing both the Kirby-Bauer and modified Kirby-Bauer methods. D-tests were conducted using clindamycin and erythromycin discs to detect inducible clindamycin resistance, while cefoxitin disc tests were utilized to ascertain methicillin resistance. Data entry was executed using Epi-Data version 4.6, and subsequent analysis was performed utilizing SPSS version 25. Bivariable and multivariable logistic regression analyses were employed to identify associated factors. An adjusted odds ratio at a 95% confidence interval with a P-value of < 0.05 was considered statistically significant., Results: The overall nasopharyngeal carriage rate of Gram-positive bacteria was 296/424 (69.8%, 95% CI: 65.3-74.0). Staphylococcus aureus was the most prevalent 122/424 (28.8%), followed by Streptococcus pneumoniae 92/424 (21.7%). Methicillin resistance was observed in 19/122 (15.6%) of S. aureus and 3/60 (5%) of coagulase-negative staphylococcus (CoNS) species. Inducible clindamycin resistance was 10/122 (8.2%) in S. aureus and 4/53 (7.5%) in coagulase-negative staphylococcus species. Multidrug resistance was found in 146/296 (49.3%, 95% CI: 43.6-55.0) of the isolates. Associated factors with a bacterial carriage were large family size (AOR = 3.061, 95% CI: 1.595-5.874, P = 0.001), having siblings under five years old (AOR = 1.991, 95% CI: 1.196-3.313, P = 0.008), indoor cooking (AOR = 2.195, 95% CI: 1.275-3.778, P = 0.005), an illiterate mother (AOR = 3.639, 95% CI: 1.691-7.829, P = 0.001), and hospital visits (AOR = 2.690, 95% CI: 1.405-5.151, P = 0.003)., Conclusion: The study found a high nasopharyngeal carriage of Gram-positive bacteria in outpatient children, including notable levels of methicillin-resistant S. aureus and multi-drug-resistant isolates. Clindamycin, rifampin, and erythromycin were the most effective antimicrobials for the tested isolates. Factors contributing to bacterial carriage include visits to healthcare facilities, larger family sizes, having younger siblings, maternal illiteracy, and indoor cooking. This emphasizes the need for methicillin-resistant S. aureus surveillance in pediatric outpatient settings and community health education, especially for children's guardians. Additionally, improving household ventilation by separating kitchens from sleeping areas and regular screening of younger siblings in healthcare environments were recommended to reduce bacterial transmission within family members. The study also called for studies with advanced procedures like minimum inhibitory concentration testing and molecular characterization to better comprehend the resistance patterns and genes in circulating bacteria., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Birhanu 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.)

The cell wall is an indispensable element of bacterial cells and a long-known target of many antibiotics. Penicillin, the first discovered beta-lactam antibiotic inhibiting the synthesis of cell walls, was successfully used to cure many bacterial infections. Unfortunately, pathogens eventually developed resistance to it. This started an arms race, and while novel beta-lactams, either natural or (semi)synthetic, were discovered, soon upon their application, bacteria were developing resistance. Currently, we are facing the threat of losing the race since more and more multidrug-resistant (MDR) pathogens are emerging. Therefore, there is an urgent need for developing novel approaches to combat MDR bacteria. The cell wall is a reasonable candidate for a target as it differentiates not only bacterial and human cells but also has a specific composition unique to various groups of bacteria. This ensures the safety and specificity of novel antibacterial agents that target this structure. Due to the shortage of low-molecular-weight candidates for novel antibiotics, attention was focused on peptides and proteins that possess antibacterial activity. Here, we describe proteinaceous agents of various origins that target bacterial cell wall, including bacteriocins and phage and bacterial lysins, as alternatives to classic antibiotic candidates for antimicrobial drugs. Moreover, advancements in protein chemistry and engineering currently allow for the production of stable, specific, and effective drugs. Finally, we introduce the concept of selective targeting of dangerous pathogens, exemplified by staphylococci, by agents specifically disrupting their cell walls.

Bacterial infections have been a serious threat to mankind throughout history. Natural antimicrobial peptides (AMPs) and their membrane disruption mechanism have generated immense interest in the design and development of synthetic mimetics that could overcome the intrinsic drawbacks of AMPs, such as their susceptibility to proteolytic degradation and low bioavailability. Herein, by exploiting the self-assembly and pore-forming capabilities of sequence-defined peptoids, we discovered a family of low-molecular weight peptoid antibiotics that exhibit excellent broad-spectrum activity and high selectivity toward a panel of clinically significant Gram-positive and Gram-negative bacterial strains, including vancomycin-resistant Enterococcus faecalis (VREF), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), Escherichia coli , Pseudomonas aeruginosa , and Klebsiella pneumoniae . Tuning the peptoid side chain chemistry and structure enabled us to tune the efficacy of antimicrobial activity. Mechanistic studies using transmission electron microscopy (TEM), bacterial membrane depolarization and lysis, and time-kill kinetics assays along with molecular dynamics simulations reveal that these peptoids kill both Gram-positive and Gram-negative bacteria through a membrane disruption mechanism. These robust and biocompatible peptoid-based antibiotics can provide a valuable tool for combating emerging drug resistance.

Antimicrobial resistance is a critical global health issue, with rising resistance among bacteria and fungi. Marine organisms have emerged as promising, but underexplored, sources of new antimicrobial agents. Among them, marine polychaetes, such as Halla parthenopeia , which possess chemical defenses, could attract significant research interest. This study explores the antimicrobial properties of hallachrome, a unique anthraquinone found in the purple mucus of H. parthenopeia , against Gram-negative bacteria ( Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 9027), Gram-positive bacteria ( Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228), and the most common human fungal pathogen Candida albicans ATCC 10231. Antibacterial susceptibility testing revealed that Gram-negative bacteria were not inhibited by hallachrome at concentrations ≤2 mM. However, Gram-positive bacteria showed significant growth inhibition at 0.12-0.25 mM, while C. albicans was inhibited at 0.06 mM. Time-kill studies demonstrated dose-dependent growth inhibition of susceptible strains by hallachrome, which exerted its effect by altering the membrane permeability of C. albicans , E. faecalis , and S. epidermidis after 6 h and S. aureus after 24 h. Additionally, hallachrome significantly reduced biofilm formation and mature biofilm in S. aureus , E. faecalis , and C. albicans . Additionally, it inhibited hyphal growth in C. albicans . These findings highlight hallachrome's potential as a novel antimicrobial agent, deserving further exploration for clinical experimentation.

Introduction: Bloodstream infections are a significant threat to soldiers wounded in combat and contribute to preventable deaths. Novel and combination therapies that can be delivered on the battlefield or in lower roles of care are urgently needed to address the threat of bloodstream infection among military personnel. In this manuscript, we tested the antibacterial capability of silver ions (Ag+), with long-appreciated antibacterial properties, against ESKAPEE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, and Escherichia coli) pathogens., Materials and Methods: We used the GENESYS (RAIN LLC) device to deliver Ag+ to Gram-positive and Gram-negative ESKAPEE organisms grown in broth, human blood, and serum. Following the Ag+ treatment, we quantified the antibacterial effects by quantifying colony-forming units., Results: We found that Ag+ was bactericidal against 5 Gram-negative organisms, K pneumoniae, A baumannii, P aeruginosa, E cloacae, and E coli, and bacteriostatic against 2 Gram-positive organisms, E faecium and S aureus. The whole blood and serum inhibited the bactericidal activity of Ag+ against a common agent of bloodstream infection, P aeruginosa. Finally, when Ag+ was added in conjunction with antibiotic in the presence of whole blood, there was no significant effect of Ag+ over antibiotic alone., Conclusions: Our results confirmed that Ag+ has broad-spectrum antibacterial properties. However, the therapeutic value of Ag+ may not extend to the treatment of bloodstream infections because of the inhibition of Ag+ activity in blood and serum., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Antimicrobial photodynamic treatment (aPDT) offers an alternative option for combating microbial pathogens, and in this way, addressing the challenges of growing antimicrobial resistance. In this promising and effective approach, cationic porphyrins and related macrocycles have emerged as leading photosensitizers (PS) for aPDT. In general, their preparation occurs via N -alkylation of nitrogen-based moieties with alkyl halides, which limits the ability to fine-tune the features of porphyrin-based PS. Herein, is reported that the conjugation of porphyrin macrocycles with triphenylphosphonium units created a series of effective cationic porphyrin-based PS for aPDT. The presence of positive charges at both the porphyrin macrocycle and triphenylphosphonium moieties significantly enhances the photodynamic activity of porphyrin-based PS against both Gram-positive and Gram-negative bacterial strains. Moreover, bacterial photoinactivation is achieved with a notable reduction in irradiation time, exceeding 50%, compared to 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin ( TMPyP ), used as the reference and known as good PS. The improved capability of the porphyrin macrocycle to generate singlet oxygen combined with the enhanced membrane interaction promoted by the presence of triphenylphosphonium moieties represents a promising approach to developing porphyrin-based PS with enhanced photosensitizing activity.

Microbial infections pose a significant global health threat, affecting millions of individuals and leading to substantial mortality rates. The increasing resistance of microorganisms to conventional treatments requires the development of novel antimicrobial agents. Pyrroloquinoline quinone (PQQ), a natural medicinal drug involved in various cellular processes, holds promise as a potential antimicrobial agent. In the present study, our aim was, for the first time, to explore the antimicrobial activity of PQQ against 29 pathogenic microbes, including 13 fungal strains, 8 Gram-positive bacteria, and 8 Gram-negative bacteria. Our findings revealed potent antifungal properties of PQQ, particularly against Syncephalastrum racemosum , Talaromyces marneffei , Candida lipolytica , and Trichophyton rubrum . The MIC values varied between fungal strains, and T. marneffei exhibited a lower MIC, indicating a greater susceptibility to PQQ. In addition, PQQ exhibited notable antibacterial activity against Gram-positive and -negative bacteria, with a prominent inhibition observed against Staphylococcus epidermidis , Proteus vulgaris , and MRSA strains. Remarkably, PQQ demonstrated considerable biofilm inhibition against the MRSA, S. epidermidis , and P. vulgaris strains. Transmission electron microscopy (TEM) studies revealed that PQQ caused structural damage and disrupted cell metabolism in bacterial cells, leading to aberrant morphology, compromised cell membrane integrity, and leakage of cytoplasmic contents. These findings were further affirmed by shotgun proteomic analysis, which revealed that PQQ targets several important cellular processes in bacteria, including membrane proteins, ATP metabolic processes, DNA repair processes, metal-binding proteins, and stress response. Finally, detailed molecular modeling investigations indicated that PQQ exhibits a substantial binding affinity score for key microbial targets, including the mannoprotein Mp1P, the transcriptional regulator TcaR, and the endonuclease PvuRTs1I. Taken together, our study underscores the effectiveness of PQQ as a broad-spectrum antimicrobial agent capable of combating pathogenic fungi and bacteria, while also inhibiting biofilm formation and targeting several critical biological processes, making it a promising therapeutic option for biofilm-related infections., Competing Interests: The authors affirm that they are not aware of any personal or financial conflicts that would have seemed to affect the findings of this study&rsquo;s research.

Due to envelope differences between Gram-positive and Gram-negative bacteria, engineering precision bactericidal contractile nanomachines requires atomic-level understanding of their structures; however, only those killing Gram-negative bacteria are currently known. Here, we report the atomic structures of an engineered diffocin, a contractile syringe-like molecular machine that kills the Gram-positive bacterium Clostridioides difficile. Captured in one pre-contraction and two post-contraction states, each structure fashions six proteins in the bacteria-targeting baseplate, two proteins in the energy-storing trunk, and a collar linking the sheath with the membrane-penetrating tube. Compared to contractile machines targeting Gram-negative bacteria, major differences reside in the baseplate and contraction magnitude, consistent with target envelope differences. The multifunctional hub-hydrolase protein connects the tube and baseplate and is positioned to degrade peptidoglycan during penetration. The full-length tape measure protein forms a coiled-coil helix bundle homotrimer spanning the entire diffocin. Our study offers mechanical insights and principles for designing potent protein-based precision antibiotics., (© 2024. The Author(s).)

Recently, pharmaceutical research has been focused on the design of new antibacterial drugs with higher selectivity towards several strains. Major issues concern the possibility to obtain compounds with fewer side effects, at the same time effectively overcoming the problem of antimicrobial resistance. Several solutions include the synthesis of new pharmacophores starting from piperazine or morpholine core units. Mass spectrometry-based techniques offer important support for the structural characterization of newly synthesized compounds to design safer and more effective drugs for various medical conditions. Here, two new piperazine derivatives and four new morpholine derivatives were synthesized and structurally characterized through a combined approach of Fourier transform-ion cyclotron resonance (FT-ICR) and Linear Trap Quadrupole (LTQ) mass spectrometry. The support of both high-resolution and low-resolution mass spectrometric data namely accurate mass measurements, isotopic distribution and MS n spectra, was crucial to confirm the success of the synthesis. These compounds were further evaluated for inhibitory activity against a total of twenty-nine Gram-positive and Gram-negative bacteria to determine the action spectrum and the antimicrobial effectiveness. Results demonstrated compounds' antimicrobial activity against many tested bacterial species, providing an inhibitory effect linked to different chemical structure and suggesting that the new-synthesized derivatives could be considered as promising antimicrobial agents., 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 B.V. All rights reserved.)

One interesting field of research in the view of developing novel surfactants for pharmaceutical and cosmetic applications is the design of amphiphiles showing further bioactive properties in addition to those commonly displayed by surface-active compounds. We propose here the chemical synthesis, and characterization of 1-o-tolyl alkyl biguanide derivatives, having different lengths of the hydrocarbon chain (C3, C6, and C10), and showing surface active and antibacterial/disinfectant activities toward both Gram-positive and Gram-negative bacteria. Both surface active properties in terms of critical micelle concentration (CMC) and surface tension at CMC (γCMC), as well as the antimicrobial activity in terms of minimum inhibitory concentrations (MICs), were strongly dependent on the length of the hydrocarbon chain. Particularly, the C6 and C10 derivatives have a good ability to decrease surface tension (γCMC <40 mN/m) at low concentrations (CMC < 12 mM) and a satisfactory antibacterial effect (MIC values between 0.230 and 0.012 mM against S. aureus strains and between 0.910 and 0.190 against P.aeruginosa strains). Interestingly, these compounds showed a disinfectant activity at the tested concentrations that was comparable to that of the reference compound chlorhexidine digluconate. All these results support the possible use of these amphiphilic compounds as antibacterial agents and disinfectants in pharmaceutical or cosmetic formulations., 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 B.V.)

Strategies to increase the efficacy and/or expand the spectrum of activity of existing antibiotics provide a potentially fast path to clinically address the growing crisis of antibiotic-resistant infections. Here, we report the synthesis, antibacterial efficacy, and mechanistic activity of an unprecedented class of biguanide-antibiotic conjugates. Our lead biguanide-vancomycin conjugate, V-C6-Bg-PhCl ( 5e ), induces highly effective cell killing with up to a 2 orders-of-magnitude improvement over its parent compound, vancomycin ( V ), against vancomycin-resistant enterococcus . V-C6-Bg-PhCl ( 5e ) also exhibits improved activity against mycobacteria and each of the ESKAPE pathogens, including the Gram-negative organisms. Furthermore, we uncover broad-spectrum killing activity against biofilm-associated Gram-positive and Gram-negative bacteria as well as mycobacteria not observed for clinically used antibiotics such as oritavancin. Mode-of-action studies reveal that vancomycin-like cell wall synthesis inhibition with improved efficacy attributed to enhanced engagement at vancomycin binding sites through biguanide association with relevant cell-surface anions for Gram-positive and Gram-negative bacteria. Due to its potency, remarkably broad activity, and lack of acute mammalian cell toxicity, V-C6-Bg-PhCl ( 5e ) is a promising candidate for treating antibiotic-resistant infections and notoriously difficult-to-treat slowly growing and antibiotic-tolerant bacteria associated with chronic and often incurable infections. More generally, this study offers a new strategy (biguanidinylation) to enhance antibiotic activity and facilitate clinical entry.

In this paper, three different Zn(II) complexes with ( E )-2-(2-(1-(6-bromopyridin-2-yl)ethylidene)hydrazinyl)- N , N , N -trimethyl-2-oxoethan-1-aminium chloride (HLCl) have been synthesized and characterized by single crystal X-ray diffraction, elemental analysis, IR and NMR spectroscopy. All complexes are mononuclear, with the ligand (L) coordinated in a deprotonated formally neutral zwitterionic form via NNO donor set atoms. Complex 1 forms an octahedral geometry with the composition [ZnL 2 ](BF 4 ) 2 , while complexes 2 [ZnL(NCO) 2 ] and 3 [ZnL(N 3 ) 2 ] form penta-coordinated geometry. Density functional theory (DFT) calculations were performed to enhance our understanding of the structures of the synthesized complexes and the cytotoxic activity of the complexes was tested against five human cancer cell lines (HeLa, A549, MDA-MB-231, K562, LS 174T) and normal human fibroblasts MRC-5. Additionally, antibacterial and antifungal activity of these complexes was tested against a panel of Gram-negative and Gram-positive bacteria, two fungal strains, and a yeast strain. It is noteworthy that all three complexes show selective antifungal activity comparable to that of amphotericin B. Molecular docking analysis predicted that geranylgeranyl pyrophosphate synthase, an enzyme essential for sterol biosynthesis, is the most likely target for inhibition by the tested complexes.

Endophytic bacteria found in marine macroalgae have been studied for their potential antimicrobial activity, consequently, they could serve as a valuable source of bioactive compounds to control pathogenic bacteria, yeasts, and fungi. Algae endophytic bacteria were isolated from Caulerpa sp., Ulva sp., Ahnfeltiopsis sp., and Chondracantus chamissoi from Yacila and Cangrejo Beaches (Piura, Peru). Antimicrobial assays against pathogenic bacteria were evaluated using cross-culture, over-plate, and volatile organic compound tests. Afterward, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of selected crude extracts were determined, also ITS molecular analysis, antifungal activity, and PCR of iturin, fengycin, and surfactin genes were performed for bacteria strains exhibiting better activity. Forty-six algae endophytic bacteria were isolated from algae. Ten strains inhibited gram-positive pathogenic bacteria (Enterococcus faecalis, Staphylococcus epidermidis, S. aureus, and Listeria monocytogenes), and 12 inhibited gram-negative bacteria (Escherichia coli and Salmonella enteric sv typhimurium). Bacteria with better activity belong to Bacillus sp., Kluyvera ascorbata, Pantoea agglomerans, Leclercia adecarboxylata, and Enterobacter sp., which only four showed antifungal activities against Candida albicans, C. tropicalis, Colletotrichium sp., Fusarium sp., Fusarium oxysporum, and Alternaria sp. Furthermore, K. ascorbata YAFE21 and Bacillus sp. YCFE4 exhibited iturin and fengycin genes. The results indicate that the algae endophytic bacteria found in this study, particularly K. ascorbata YAFE21, Bacillus sp. YCFR6, L. adecarboxylata CUFE2, Bacillus sp. YUFE8, Enterobacter sp. YAFL1, and P. agglomerans YAFL6, could be investigated as potential producers of antimicrobial compounds due to their broad activity against various microorganisms., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)