Cell division factor ZapE regulates Pseudomonas aeruginosa biofilm formation by impacting the pqs quorum sensing system

Liu，Xi1,2,3; Jia，Minlu2; Wang，Jing2; Cheng，Hang2; Cai，Zhao2; Yu，Zhaoxiao1; Liu，Yang4; Ma，Luyan Z.1; Zhang，Lianhui3; Zhang，Yingdan2,5; Yang，Liang2,5

2023-03-01

10.1002/mlf2.12059

mLife   影响因子和分区

2097-1699

2770-100X

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.

biofilm Pseudomonas aeruginosa Pseudomonas quinolone signal transposon-insertion site sequencing (Tn-seq) ZapE

ESCI

英语

通讯

Guangdong Natural Science Foundation for Distinguished Young Scholar[2020B1515020003] ; Shenzhen Science and Technology Program[KQTD20200909113758004] ; China Postdoctoral Science Foundation[2020M672649] ; National Natural Science Foundation of China["91951204","32200155"] ; Guangdong Basic and Applied Basic Research Foundation["2019A1515110640","2020A1515010316"]

Microbiology

Microbiology

WOS:001153996800007

WILEY

2-s2.0-85152645193

Scopus

1.State Key Laboratory of Microbial Resources,Institute of Microbiology,Chinese Academy of Sciences,Beijing,China
2.Key University Laboratory of Metabolism and Health of Guangdong,School of Medicine,Southern University of Science and Technology,Shenzhen,China
3.Guangdong Province Key Laboratory of Microbial Signals and Disease Control,Integrative Microbiology Research Center,South China Agricultural University,Guangzhou,China
4.Medical Research Center,Southern University of Science and Technology Hospital,Shenzhen,China
5.Shenzhen Third People's Hospital,National Clinical Research Center for Infectious Disease,The Second Affiliated Hospital of Southern University of Science and Technology,Shenzhen,China

Liu，Xi,Jia，Minlu,Wang，Jing,et al. Cell division factor ZapE regulates Pseudomonas aeruginosa biofilm formation by impacting the pqs quorum sensing system[J]. mLife,2023,2(1):28-42.

Liu，Xi.,Jia，Minlu.,Wang，Jing.,Cheng，Hang.,Cai，Zhao.,...&Yang，Liang.(2023).Cell division factor ZapE regulates Pseudomonas aeruginosa biofilm formation by impacting the pqs quorum sensing system.mLife,2(1),28-42.

Liu，Xi,et al."Cell division factor ZapE regulates Pseudomonas aeruginosa biofilm formation by impacting the pqs quorum sensing system".mLife 2.1(2023):28-42.