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

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外文摘要：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 ΔzapE mutant lost fitness against the wild-type PAO1 strain in biofilms and its production of 2-heptyl-3-hydroxy-4(1 H)-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.

外文关键词：

biofilmPseudomonas aeruginosaPseudomonas quinolone signaltransposon-insertion site sequencing(Tn-seq)ZapE

作者：

Xi Liu、Minlu Jia、Jing Wang、Hang Cheng、Zhao Cai、Zhaoxiao Yu、Yang Liu、Luyan Z.Ma、Lianhui Zhang、Yingdan Zhang、Liang Yang

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作者单位：

State Key Laboratory of Microbial Resources,Institute of Microbiology,Chinese Academy of Sciences,Beijing,China

Key University Laboratory of Metabolism and Health of Guangdong,School of Medicine,Southern University of Science and Technology,Shenzhen,China

Guangdong Province Key Laboratory of Microbial Signals and Disease Control,Integrative Microbiology Research Center,South China Agricultural University,Guangzhou,China

Medical Research Center,Southern University of Science and Technology Hospital,Shenzhen,China

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

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基金：

Southern University of Science and Technology for the assistance on SPR experimentShenzhen Science and Technology ProgramChina Postdoctoral science FoundationNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaGuangdong Basic and Applied Basic Research FoundationGuangdong Basic and Applied Basic Research Foundation

项目编号：

2020B1515020003KQTD202009091137580042020M67264991951204322001552019A15151106402020A1515010316

出版年：

2023

DOI：

10.1002/mlf2.12059

微生物(英文)

ISSN：

年,卷(期)：2023.2(1)

参考文献量56