4.6 Article

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

期刊

MICROBIOLOGY SPECTRUM
卷 -, 期 -, 页码 -

出版社

AMER SOC MICROBIOLOGY
DOI: 10.1128/spectrum.00547-22

关键词

methicillin-resistant Staphylococcus aureus; WYBQ-4; PBP2a; bactericidal agent

资金

  1. Science Foundation of Jilin Province, China [20220101286JC]
  2. National Natural Science Foundation of China [32273058]
  3. National Key Research and Development Program of China [2018YFD0500300]

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Antibiotic resistance is spreading rapidly, causing a public health crisis. There is an urgent need for new antimicrobial agents against MRSA. WYBQ-4 has been found to have potent bactericidal activity against MRSA and shows significant efficacy in in vitro and in vivo experiments. This compound has the potential to control MRSA infection.
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. 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.

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