1. rpoS-mutation variants are selected in Pseudomonas aeruginosa biofilms under imipenem pressure
- Author
-
Ke Wang, Lian-Hui Zhang, Xiangke Duan, Moxiao Liu, Liang Yang, Yang Liu, Yingdan Zhang, Zhao Cai, Yumei Liu, and Yanrong Pan
- Subjects
Imipenem ,QH301-705.5 ,Mutant ,Virulence ,QD415-436 ,Biology ,medicine.disease_cause ,Biochemistry ,General Biochemistry, Genetics and Molecular Biology ,Microbiology ,Sigma factor RpoS ,03 medical and health sciences ,chemistry.chemical_compound ,Pyocyanin ,medicine ,Experimental biofilm evolution ,Biology (General) ,030304 developmental biology ,Cyclic-di-GMP ,0303 health sciences ,030306 microbiology ,Pseudomonas aeruginosa ,Point mutation ,Research ,Biofilm ,biochemical phenomena, metabolism, and nutrition ,chemistry ,Biofilms ,rpoS ,TP248.13-248.65 ,Biotechnology ,medicine.drug - Abstract
Background Pseudomonas aeruginosa is a notorious opportunistic pathogen causing various types of biofilm-related infections. Biofilm formation is a unique microbial strategy that allows P. aeruginosa to survive adverse conditions such as antibiotic treatment and human immune clearance. Results In this study, we experimentally evolved P. aeruginosa PAO1 biofilms for cyclic treatment in the presence of high dose of imipenem, and enriched hyperbiofilm mutants within six cycles in two independent lineages. The competition assay showed that the evolved hyperbiofilm mutants can outcompete the ancestral strain within biofilms but not in planktonic cultures. Whole-genome sequencing analysis revealed the hyperbiofilm phenotype is caused by point mutations in rpoS gene in all independently evolved mutants and the same mutation was found in P. aeruginosa clinical isolates. We further showed that mutation in rpoS gene increased the intracellular c-di-GMP level by turning on the expression of the diguanylate cyclases. Mutation in rpoS increased pyocyanin production and virulence in hyperbiofilm variants. Conclusion Here, our study revealed that antibiotic treatment of biofilm-related P. aeruginosa infections might induce a hyperbiofilm phenotype via rpoS mutation, which might partially explain antimicrobial treatment failure of many P. aeruginosa biofilm-related infections.
- Published
- 2021