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10 26, 2022;10 (5): e0054722.

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

Shuhan Guan, Hangqian Yu, Hua Xiang, Li Wang, Jingyu Liu, Anfang Wu, Jianze Zheng, Hongbo Dong, Lin Wang, Dacheng Wang
Author Information
  1. Shuhan Guan: College of Animal Science, Jilin Universitygrid.64924.3d, Changchun, China.
  2. Hangqian Yu: College of Animal Science, Jilin Universitygrid.64924.3d, Changchun, China.
  3. Hua Xiang: College of Animal Medicine, Jilin Agricultural University, Changchun, China.
  4. Li Wang: College of Animal Science, Jilin Universitygrid.64924.3d, Changchun, China.
  5. Jingyu Liu: College of Animal Science, Jilin Universitygrid.64924.3d, Changchun, China.
  6. Anfang Wu: College of Animal Science, Jilin Universitygrid.64924.3d, Changchun, China.
  7. Jianze Zheng: College of Animal Science, Jilin Universitygrid.64924.3d, Changchun, China.
  8. Hongbo Dong: School of Pharmacy, Chengdu University, Chengdu, China.
  9. Lin Wang: State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin Universitygrid.64924.3d, Changchun, China.
  10. Dacheng Wang: College of Animal Science, Jilin Universitygrid.64924.3d, Changchun, China. ORCID
PMID: 36098533 DOI: 10.1128/spectrum.00547-22

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 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 and , indicating that it is a promising compound 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. 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 efficacy in MRSA-induced mouse models. Subsequently, we further revealed its antibacterial mechanism. In conclusion, WYBQ-4 has a significant bactericidal effect and , indicating that it is a promising compound to control MRSA infection.

Keywords

PBP2a WYBQ-4 bactericidal agent methicillin-resistant Staphylococcus aureus

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MeSH Term

Mice
Animals
Methicillin-Resistant Staphylococcus aureus
Penicillin-Binding Proteins
Microbial Sensitivity Tests
Anti-Bacterial Agents
Cephalosporins
Staphylococcal Infections

Chemicals

Penicillin-Binding Proteins
Anti-Bacterial Agents
Cephalosporins
Journal Article Research Support, Non-U.S. Gov't
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Word Cloud

Created with Highcharts 10.0.0MRSAWYBQ-4bactericidalpotentinfectionStaphylococcusaureusantibacterialagentactivityclinicalefficacymodelhealthNovelantimicrobialagentsurgentlydevelopedstudyinvestigatedeffectiveefficiencyUSA300isolatestrainsshowedMRSA-inducedmousenewPBP2aconclusionsignificanteffectindicatingpromisingcompoundcontrolMethicillin-resistantmultidrug-resistantpathogencurrentlyposesseriousthreatglobaladditionexhibitedlowcytotoxicitywithouthemolyticaccordingsafetyevaluationImportantlypneumoniasystemicintramuscularcephalosporinassociatedhighaffinitypenicillin-bindingproteinsPBP1PBP2PBP3PBP4evaluatedcompetitionassayusingbocillinreporterAntibioticresistancespreadingfasterintroductioncompoundspracticecausingpubliccrisisbacteriostaticmodelsSubsequentlyrevealedmechanismWYBQ-4:NewBactericidalAgentMethicillin-Resistantmethicillin-resistant

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