The Burkholderia pseudomallei Proteins BapA and BapC Are Secreted TTSS3 Effectors and BapB Levels Modulate Expression of BopE

PLoS One. 2015 Dec 1;10(12):e0143916. doi: 10.1371/journal.pone.0143916. eCollection 2015.

Abstract

Many Gram-negative pathogens use a type III secretion system (TTSS) for the injection of bacterial effector proteins into host cells. The injected effector proteins play direct roles in modulation of host cell pathways for bacterial benefit. Burkholderia pseudomallei, the causative agent of melioidosis, expresses three different TTSSs. One of these systems, the TTSS3, is essential for escape from host endosomes and therefore intracellular survival and replication. Here we have characterized three putative TTSS3 proteins; namely BapA, BapB and BapC. By employing a tetracysteine (TC)-FlAsH™ labelling technique to monitor the secretion of TC-tagged fusion proteins, BapA and BapC were shown to be secreted during in vitro growth in a TTSS3-dependant manner, suggesting a role as TTSS3 effectors. Furthermore, we constructed B. pseudomallei bapA, bapB and bapC mutants and used the well-characterized TTSS3 effector BopE as a marker of secretion to show that BapA, BapB and BapC are not essential for the secretion process. However, BopE transcription and secretion were significantly increased in the bapB mutant, suggesting that BapB levels modulate BopE expression. In a BALB/c mouse model of acute melioidosis, the bapA, bapB and bapC mutants showed a minor reduction of in vivo fitness. Thus, this study defines BapA and BapC as novel TTSS3 effectors, BapB as a regulator of BopE production, and all three as necessary for full B. pseudomallei in vivo fitness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism*
  • Biological Transport / genetics
  • Burkholderia pseudomallei / genetics*
  • Burkholderia pseudomallei / metabolism*
  • Female
  • Melioidosis / genetics
  • Melioidosis / metabolism
  • Melioidosis / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Mutation / genetics
  • Virulence / genetics
  • Virulence Factors / genetics
  • Virulence Factors / metabolism

Substances

  • Bacterial Proteins
  • Virulence Factors

Grants and funding

This work was funded by Australian Research Council (AU), Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics (Grant number CE0562063); National Health and Medical Research Council (AU) (Project Grant number 545855). Jamunarani Vadivelu gratefully acknowledges receipt of a travel fellowship from the Australia-Malaysia Institute and University of Malaya High Impact Research (HIR)-MOHE project (E000013-20001). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.