2. Academic Validation
  3. Interactions between host epithelial cells and Acinetobacter baumannii promote the emergence of highly antibiotic resistant and highly mucoid strains

Interactions between host epithelial cells and Acinetobacter baumannii promote the emergence of highly antibiotic resistant and highly mucoid strains

  • Emerg Microbes Infect. 2022 Oct 13;1-49. doi: 10.1080/22221751.2022.2136534.
Wang Zhang 1 2 3,  Yue Yao 1 2 3,  Hua Zhou 4,  Jintao He 1 2 3,  Jingfen Wang 1 2 3,  Li Li 5,  Minsong Gao 6,  Xiaochen Liu 1 2 3,  Ya Shi 7,  Jinzhong Lin 5,  Jianzhao Liu 6 8,  Huan Chen 7,  Yu Feng 1 9,  Zhihui Zhou 1 2 3,  Yunsong Yu 1 2 3,  Xiaoting Hua 1 2 3
Affiliations

Affiliations

  • 1 Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 2 Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 3 Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, China.
  • 4 Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 5 State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.
  • 6 MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, China.
  • 7 Hangzhou Digital-Micro Biotech Co., Ltd., Hangzhou, Zhejiang, China.
  • 8 Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang, China.
  • 9 Department of Biophysics, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
PMID: 36227610 DOI: 10.1080/22221751.2022.2136534
Abstract

Acinetobacter baumannii is an important nosocomial pathogen. Upon colonizing a host, A. baumannii are subjected to selective pressure by immune defenses as they adapt to the host environment. However, the mechanism of this pathoadaptation is unknown. Here, we established an in vitro system to evolve A. baumannii driven by the continuous selective pressure exerted by epithelial cells, and we used a combination of experimental evolution, phenotypic characterization and multi-omics analysis to address the underlying mechanism. When continuously exposed to selective pressure by pulmonary epithelial cells, A. baumannii showed ptk mutation-mediated mucoid conversion (reduced adhesion and increased anti-phagocytic ability) by enhancement of capsular exopolysaccharide chain length; rsmG mutation-mediated deficiency of 7-methylguanosine modification in the 524th nucleotide of 16S rRNA, which increased ribosome translation efficiency; and rnaseI mutation-mediated changes in outer membrane permeability and efflux pump expression. Together, these mutations altered susceptibility to a variety of antimicrobial agents, including the novel Antibiotic cefiderocol, by regulating siderophore and siderophore-receptor biosynthesis. In conclusion, pulmonary epithelial cells modulate A. baumannii pathoadaptation, implicating the host-microbe interaction in the survival and persistence of A. baumannii.

Keywords

Acinetobacter baumannii, pathoadaptation; epithelial cell; experimental evolution.

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