Azalomycin F4a targets peptidoglycan synthesis of Gram-positive bacteria revealed by high-throughput CRISPRi-seq analysis.
Microbiol Res
; 280: 127584, 2024 Mar.
Article
en En
| MEDLINE
| ID: mdl-38157688
ABSTRACT
Azalomycin F4a is a promising 36-membered polyhydroxy macrolide that shows antibacterial activity against drug-resistant Gram-positive bacteria, but its exact working mechanism remains to be elusive. Here, we isolated the azalomycin F4a product from a Streptomyces solisilvae and demonstrated its antibacterial activity against Gram-positive pathogens including Streptococcus pneumoniae, Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA). We further showed that combination of azalomycin F4a with methicillin has an additive antimicrobial effect on MRSA, where the minimal inhibitory concentrations (MIC) of methicillin to MRSA was decreased by 1000-fold in the presence of sublethal concentration of azalomycin F4a. A CRISPRi-seq based whole genome screen was employed to identify the potential targets of azalomycin F4a, which revealed that peptidoglycan synthesis (PGS) was inhibited by azalomycin F4a. Furthermore, azalomycin F4a treatment could significantly impair S. aureus biofilm formation. Our research highlights that cell wall synthesis is an additional target for novel classes of macrolide besides ribosome.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Staphylococcus aureus Resistente a Meticilina
Idioma:
En
Revista:
Microbiol Res
Asunto de la revista:
MICROBIOLOGIA
/
SAUDE AMBIENTAL
Año:
2024
Tipo del documento:
Article
País de afiliación:
China