Pseudomonas aeruginosa Citrate Synthase GltA Influences Antibiotic Tolerance and the Type III Secretion System through the Stringent Response
Hao Chen, Xuetao Gong, Zheng Fan, Yushan Xia, Yongxin Jin, Fang Bai, Zhihui Cheng, Xiaolei Pan, Weihui Wu
Abstract
Rising antimicrobial resistance imposes a severe threat to human health. It is urgent to develop novel antimicrobial strategies by understanding bacterial regulation of virulence and antimicrobial resistance determinants. The stringent response plays an essential role in virulence and antibiotic tolerance. Pseudomonas aeruginosa is an opportunistic pathogen that causes acute and chronic infections in humans. The bacterium produces an arsenal of virulence factors and is highly resistant to a variety of antibiotics. In this study, we provide evidence that citrate synthase GltA plays a critical role in P. aeruginosa metabolism and influences the antibiotic tolerance and virulence. We further reveal a role of the stringent response in the regulation of the antibiotic tolerance and virulence. The significance of this work is in elucidation of novel regulatory pathways that control both antibiotic tolerance and virulence in P. aeruginosa.