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WYBQ-4: a New Bactericidal Agent against Methicillin-Resistant Staphylococcus aureus.

ABSTRACT: Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant pathogen that currently poses a serious threat to global health. Novel antimicrobial agents against MRSA are urgently being developed. In this study, we investigated WYBQ-4, which is an effective antibacterial agent with potent bactericidal activity and bactericidal efficiency against MRSA USA300 and clinical isolate strains. In addition, WYBQ-4 exhibited low cytotoxicity without hemolytic activity according to a safety evaluation. Importantly, WYBQ-4 showed potent in vivo efficacy in an MRSA-induced mouse pneumonia model, systemic infection model, and intramuscular infection model. The efficacy of this new cephalosporin against MRSA was associated with a high affinity for penicillin-binding proteins (PBP1, PBP2, PBP3, PBP4, PBP2a) evaluated in a competition assay using bocillin as a reporter. In conclusion, WYBQ-4 has a significant bactericidal effect in vitro and in vivo, indicating that it is a promising compound to control MRSA infection. IMPORTANCE Antibiotic resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis. Novel antimicrobial agents against MRSA are urgently being developed. In this study, we investigated WYBQ-4, which is an effective antibacterial agent with potent bacteriostatic activity and bactericidal efficiency against MRSA USA300 and clinical isolate strains. WYBQ-4 showed potent in vivo efficacy in MRSA-induced mouse models. Subsequently, we further revealed its antibacterial mechanism. In conclusion, WYBQ-4 has a significant bactericidal effect in vitro and in vivo, indicating that it is a promising compound to control MRSA infection.

SUBMITTER: Guan S

PROVIDER: S-EPMC9603521 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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WYBQ-4: a New Bactericidal Agent against Methicillin-Resistant Staphylococcus aureus.

Guan Shuhan S Yu Hangqian H Xiang Hua H Wang Li L Liu Jingyu J Wu Anfang A Zheng Jianze J Dong Hongbo H Wang Lin L Wang Dacheng D

Microbiology spectrum 20220913 5

Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant pathogen that currently poses a serious threat to global health. Novel antimicrobial agents against MRSA are urgently being developed. In this study, we investigated WYBQ-4, which is an effective antibacterial agent with potent bactericidal activity and bactericidal efficiency against MRSA USA300 and clinical isolate strains. In addition, WYBQ-4 exhibited low cytotoxicity without hemolytic activity according to a safety ...[more]

PMID: 36098533

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Project description:BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) has been responsible for serious hospital infections worldwide. Nanomaterials are an alternative to conventional antibiotic compounds, because bacteria are unlikely to develop microbial resistance against nanomaterials. In the past decade, graphene oxide (GO) has emerged as a material that is often used to support and stabilize silver nanoparticles (AgNPs) for the preparation of novel antibacterial nanocomposites. In this work, we report the synthesis of the graphene-oxide silver nanocomposite (GO-Ag) and its antibacterial activity against relevant microorganisms in medicine.Materials and methodsGO-Ag nanocomposite was synthesized through the reduction of silver ions (Ag(+)) by sodium citrate in an aqueous GO dispersion, and was extensively characterized using ultraviolet-visible absorption spectroscopy, X-ray diffraction, thermogravimetric analysis, X-ray photoelectron spectroscopy, and transmission electron microscopy. The antibacterial activity was evaluated by microdilution assays and time-kill experiments. The morphology of bacterial cells treated with GO-Ag was investigated via transmission electron microscopy.ResultsAgNPs were well distributed throughout GO sheets, with an average size of 9.4±2.8 nm. The GO-Ag nanocomposite exhibited an excellent antibacterial activity against methicillin-resistant S. aureus, Acinetobacter baumannii, Enterococcus faecalis, and Escherichia coli. All (100%) MRSA cells were inactivated after 4 hours of exposure to GO-Ag sheets. In addition, no toxicity was found for either pristine GO or bare AgNPs within the tested concentration range. Transmission electronic microscopy images offered insights into how GO-Ag nanosheets interacted with bacterial cells.ConclusionOur results indicate that the GO-Ag nanocomposite is a promising antibacterial agent against common nosocomial bacteria, particularly antibiotic-resistant MRSA. Morphological injuries on MRSA cells revealed a likely loss of viability as a result of the direct contact between bacteria and the GO-Ag sheets.

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WYBQ-4: a New Bactericidal Agent against Methicillin-Resistant Staphylococcus aureus.

Publications

WYBQ-4: a New Bactericidal Agent against Methicillin-Resistant Staphylococcus aureus.

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