Perturbation of the two-component signal transduction system, BprRS, results in attenuated virulence and motility defects in Burkholderia pseudomallei

BMC Genomics

Research Article

Brenda Govan¹  Elizabeth M. Allwood²  Stephen Watts²  Natalie R. Lazar Adler³  Puthayalai Treerat⁴  Priyangi Alwis⁵  Ben Adler⁶  John D. Boyce⁶  Deanna Deveson Lucas⁶  Marina Harper⁶  Mark Prescott⁷  Alexandra Dimitropoulos⁷  Rodney J. Devenish⁷  Paul Harrison⁸ 

[1] Department of Microbiology and Immunology, James Cook University, Townsville, Queensland, Australia;Department of Microbiology, Monash University, 19 Innovation Walk, Clayton, 3800, Victoria, Australia;Department of Microbiology, Monash University, 19 Innovation Walk, Clayton, 3800, Victoria, Australia;Core Biotechnology Services, University of Leicester, LE1 9HN, Leicester, UK;Department of Microbiology, Monash University, 19 Innovation Walk, Clayton, 3800, Victoria, Australia;Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA;Department of Microbiology, Monash University, 19 Innovation Walk, Clayton, 3800, Victoria, Australia;Faculty of Dentistry, National University of Singapore, Singapore, Singapore;Department of Microbiology, Monash University, 19 Innovation Walk, Clayton, 3800, Victoria, Australia;Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Victoria, Australia;Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Victoria, Australia;Department of Biochemistry and Molecular Biology, Monash University, Victoria, Australia;Victorian Bioinformatics Platform, Monash University, Victoria, Australia;

关键词: Burkholderia pseudomallei;    Two-component signal transduction;    Transcriptomics;    Flagella;    Virulence;   

DOI  :  10.1186/s12864-016-2668-4

 received in 2015-11-26, accepted in 2016-04-26,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundBurkholderia pseudomallei is the causative agent of melioidosis, a severe invasive disease of humans and animals. Initial screening of a B. pseudomallei signature-tagged mutagenesis library identified an attenuated mutant with a transposon insertion in a gene encoding the sensor component of an uncharacterised two-component signal transduction system (TCSTS), which we designated BprRS.ResultsSingle gene inactivation of either the response regulator gene (bprR) or the sensor histidine kinase gene (bprS) resulted in mutants with reduced swarming motility and reduced virulence in mice. However, a bprRS double mutant was not attenuated for virulence and displayed wild-type levels of motility. The transcriptomes of the bprS, bprR and bprRS mutants were compared with the transcriptome of the parent strain K96243. Inactivation of the entire BprRS TCSTS (bprRS double mutant) resulted in altered expression of only nine genes, including both bprR and bprS, five phage-related genes and bpss0686, encoding a putative 5, 10-methylene tetrahydromethanopterin reductase involved in one carbon metabolism. In contrast, the transcriptomes of each of the bprR and bprS single gene mutants revealed more than 70 differentially expressed genes common to both mutants, including regulatory genes and those required for flagella assembly and for the biosynthesis of the cytotoxic polyketide, malleilactone.ConclusionsInactivation of the entire BprRS TCSTS did not alter virulence or motility and very few genes were differentially expressed indicating that the definitive BprRS regulon is relatively small. However, loss of a single component, either the sensor histidine kinase BprS or its cognate response regulator BprR, resulted in significant transcriptomic and phenotypic differences from the wild-type strain. We hypothesize that the dramatically altered phenotypes of these single mutants are the result of cross-regulation with one or more other TCSTSs and concomitant dysregulation of other key regulatory genes.

【 授权许可】

CC BY   
© Lazar Adler et al. 2016