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

• Published in: Microbiology spectrum 2022-10, Vol.10 (5), p.e0054722-e0054722
• Main Authors: Guan, Shuhan, Yu, Hangqian, Xiang, Hua, Wang, Li, Liu, Jingyu, Wu, Anfang, Zheng, Jianze, Dong, Hongbo, Wang, Lin, Wang, Dacheng
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antimicrobial Chemotherapy; bactericidal agent; Cephalosporins; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; PBP2a; Penicillin-Binding Proteins - metabolism; Penicillin-Binding Proteins - pharmacology; Research Article; Staphylococcal Infections - drug therapy; WYBQ-4
• ISSN: 2165-0497; 2165-0497
• DOI: 10.1128/spectrum.00547-22

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.