Iizuchalasin A: A Marine Fungal Metabolite With a Cage‐Like Structure That Binds TarG to Inhibit Wall Teichoic Acid Biosynthesis by Multidrug‐Resistant <i>S. aureus</i>
Abstract
ABSTRACT To address the ongoing Staphylococcus aureus drug resistance, we screened marine fungal extracts against a multidrug‐resistant strain and performed a metabolome analysis to identified new antibiotics with larger molecular size. Targeted isolation yielded eight merocytochalasans, including four new compounds ( 1 , 4 ‐ 6 ), structurally characterized by MS, NMR, and x‐ray single‐crystal diffraction data analysis. Compound 1 possessing a unique cage‐like symmetrical skeleton, effectively suppressed growth, adhesion, and virulence of methicillin‐resistant S. aureus (MRSA), demonstrated potent efficacy in reducing bacterial burden in a mouse skin infection model, and exhibited low resistance development potential. Mechanistically, 1 binds the transmembrane component of the ABC transporter TarGH, and inhibiting its ATPase activity.
Article Details
Authors (13)
Rui Zhang
Huanqin Dai
State Key Laboratory of Microbial Diversity and Innovative Utilization Beijing Key Laboratory of Antimicrobial‐Resistant Pathogen Microbiology and AI‐Empowered Containment Institute of Microbiology Chinese Academy of Sciences Beijing China
Baosong Chen
State Key Laboratory of Microbial Diversity and Innovative Utilization,Institute of Microbiology Chinese Academy of Sciences Beijing China
Haifeng Wang
Yuxi Qin
State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University
Jinwei Ren
State Key Laboratory of Microbial Diversity and Innovative Utilization
Ming Zhang
Ruopeng Yin
State Key Laboratory of Microbial Diversity and Innovative Utilization Beijing Key Laboratory of Antimicrobial‐Resistant Pathogen Microbiology and AI‐Empowered Containment Institute of Microbiology Chinese Academy of Sciences Beijing China
Jingzu Sun
State Key Laboratory of Microbial Diversity and Innovative Utilization Beijing Key Laboratory of Antimicrobial‐Resistant Pathogen Microbiology and AI‐Empowered Containment Institute of Microbiology Chinese Academy of Sciences Beijing China
Junjie Han
Yaojun Tong
State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University
Yonghui Zhang
Hongwei Liu
The Australian Centre for Microscopy and Microanalysis