Outer membrane permeability of mcr-positive bacteria reveals potent synergy of colistin and macromolecular antibiotics against colistin-resistant Acinetobacter baumannii

• Published in: Frontiers in microbiology Vol. 15; p. 1468682
• Main Authors: Li, Meisong, Ma, Furong, Zhao, Hui, Zhou, Dianrong, Liang, Lujie, Lv, Runling, Li, Jiachen, Wang, Yaxuan, Xu, Lin, Liu, Chenfei, Tian, Guo-Bao, Feng, Siyuan, Xia, Yong
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 19.11.2024
• Subjects: Acinetobacter baumannii; colistin; MCR; Microbiology; outer membrane permeability; rifampicin; rifampicin; Acinetobacter baumannii; MCR; outer membrane permeability; colistin
• ISSN: 1664-302X; 1664-302X
• DOI: 10.3389/fmicb.2024.1468682

Colistin (CT) is the last-resort of antibiotic against multidrug-resistance (MDR) Acinetobacter baumannii ( A. baumannii ) infection. However, colistin resistance is increasingly reported in A. baumannii isolates partially due to the global emergence and dissemination of plasmid-borne mobile colistin resistance ( mcr ) gene and is a threat to human health. Thus, available treatment strategies urgently required in the fight against colistin-resistant A. baumannii . Here, we showed that mcr confers damaged outer membrane (OM) permeability in A. baumannii , which could compromise the viability of A. baumannii . Consistently, A. baumannii with colistin resistance exhibits increased susceptibility to macromolecular antibiotics such as rifampicin (RIF) and erythromycin (ERY). Moreover, the combination therapy of colistin and rifampicin demonstrates efficacy against colistin-resistant A. baumannii , regardless of the presence of mcr . Altogether, our data suggest that the synergy of colistin in combination with macromolecular hydrophobic antibiotics poses a promising therapeutic alternative for colistin-resistant A. baumannii .