Cell division factor ZapE regulates Pseudomonas aeruginosa biofilm formation by impacting the pqs quorum sensing system
Xi Liu,
Minlu Jia,
Jing Wang,
Hang Cheng,
Zhao Cai,
Zhaoxiao Yu,
Yang Liu,
Luyan Z. Ma,
Lianhui Zhang,
Yingdan Zhang,
Liang Yang
Affiliations
Xi Liu
State Key Laboratory of Microbial Resources, Institute of Microbiology Chinese Academy of Sciences Beijing China
Minlu Jia
Key University Laboratory of Metabolism and Health of Guangdong, School of Medicine Southern University of Science and Technology Shenzhen China
Jing Wang
Key University Laboratory of Metabolism and Health of Guangdong, School of Medicine Southern University of Science and Technology Shenzhen China
Hang Cheng
Key University Laboratory of Metabolism and Health of Guangdong, School of Medicine Southern University of Science and Technology Shenzhen China
Zhao Cai
Key University Laboratory of Metabolism and Health of Guangdong, School of Medicine Southern University of Science and Technology Shenzhen China
Zhaoxiao Yu
State Key Laboratory of Microbial Resources, Institute of Microbiology Chinese Academy of Sciences Beijing China
Yang Liu
Medical Research Center Southern University of Science and Technology Hospital Shenzhen China
Luyan Z. Ma
State Key Laboratory of Microbial Resources, Institute of Microbiology Chinese Academy of Sciences Beijing China
Lianhui Zhang
Guangdong Province Key Laboratory of Microbial Signals and Disease Control, Integrative Microbiology Research Center South China Agricultural University Guangzhou China
Yingdan Zhang
Key University Laboratory of Metabolism and Health of Guangdong, School of Medicine Southern University of Science and Technology Shenzhen China
Liang Yang
Key University Laboratory of Metabolism and Health of Guangdong, School of Medicine Southern University of Science and Technology Shenzhen China
Abstract Pseudomonas aeruginosa is one of the leading nosocomial pathogens that causes both severe acute and chronic infections. The strong capacity of P. aeruginosa to form biofilms can dramatically increase its antibiotic resistance and lead to treatment failure. The biofilm resident bacterial cells display distinct gene expression profiles and phenotypes compared to their free‐living counterparts. Elucidating the genetic determinants of biofilm formation is crucial for the development of antibiofilm drugs. In this study, a high‐throughput transposon‐insertion site sequencing (Tn‐seq) approach was employed to identify novel P. aeruginosa biofilm genetic determinants. When analyzing the novel biofilm regulatory genes, we found that the cell division factor ZapE (PA4438) controls the P. aeruginosa pqs quorum sensing system. The ∆zapE mutant lost fitness against the wild‐type PAO1 strain in biofilms and its production of 2‐heptyl‐3‐hydroxy‐4(1H)‐quinolone (PQS) had been reduced. Further biochemical analysis showed that ZapE interacts with PqsH, which encodes the synthase that converts 2‐heptyl‐4‐quinolone (HHQ) to PQS. In addition, site‐directed mutagenesis of the ATPase active site of ZapE (K72A) abolished the positive regulation of ZapE on PQS signaling. As ZapE is highly conserved among the Pseudomonas group, our study suggests that it is a potential drug target for the control of Pseudomonas infections.
