Mobile Colistin Resistance Enzyme MCR‐3 Facilitates Bacterial Evasion of Host Phagocytosis. Issue 18 (29th July 2021)

• Record Type: Journal Article
• Authors: Yin, Wenjuan; Ling, Zhuoren; Dong, Yanjun; Qiao, Lu; Shen, Yingbo; Liu, Zhihai; Wu, Yifan; Li, Wan; Zhang, Rong; Walsh, Timothy R.; Dai, Chongshan; Li, Juan; Yang, Hui; Liu, Dejun; Wang, Yang; Gao, George Fu; Shen, Jianzhong
• Is Part Of: Advanced science. Volume 8:Issue 18(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-07-29
• Subjects: colistin -- lipid A modification -- mcr‐3 -- phagocytosis -- virulence; Science -- Periodicals; 505
• DOI: 10.1002/advs.202101336
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: Mobile colistin resistance enzyme MCR‐3 is a phosphoethanolamine transferase modifying lipid A in Gram‐negative bacteria. MCR‐3 generally mediates low‐level (≤8 mg L −1 ) colistin resistance among Enterobacteriaceae, but occasionally confers high‐level (>128 mg L −1 ) resistance in aeromonads. Herein, it is determined that MCR‐3, together with another lipid A modification mediated by the arnBCADTEF operon, may be responsible for high‐level colistin resistance in aeromonads. Lipid A is the critical site of pathogens for Toll‐like receptor 4 recognizing. However, it is unknown whether or how MCR‐3‐mediated lipid A modification affects the host immune response. Compared with the wild‐type strains, increased mortality is observed in mice intraperitoneally‐infected with mcr‐3 ‐positive Aeromonas salmonicida and Escherichia coli strains, along with sepsis symptoms. Further, mcr‐3 ‐positive strains show decreased clearance rates than wild‐type strains, leading to bacterial accumulation in organs. The increased mortality is tightly associated with the increased tissue hypoxia, injury, and post‐inflammation. MCR‐3 expression also impairs phagocytosis efficiency both in vivo and in vitro, contributing to the increased persistence of mcr‐3 ‐positive bacteria in tissues compared with parental strains. This study, for the first time, reveals a dual function of MCR‐3 in bacterial resistance and pathogenicity, which calls for caution in treating the infections caused by mcr ‐positive pathogens. Abstract : The synergistic lipid A modifications by mobile colistin resistance gene ( mcr‐3 ) and arnBCADTEF operon are responsible for high‐level colistin resistance in Aeromonas salmonicida . Both Escherichia coli and A. salmonicida strains harboring mcr‐3 suffer less phagocytosis and present enhanced pathogenicity. The dual threat, increased colistin resistance and pathogenicity, of infections caused by MCR‐producing pathogens needs considerable attention in the clinical settings.