Type VI secretion is a major virulence determinant in Burkholderia mallei

Abstract

SummaryBurkholderia mallei is a host-adapted pathogen and a category B biothreat agent. Although the B. mallei VirAG two-component regulatory system is required for virulence in hamsters, the virulence genes it regulates are unknown. Here we show with expression profiling that overexpression of virAG resulted in transcriptional activation of~60 genes, including some involved in capsule production, actin-based intracellular motility, and type VI secretion (T6S). The 15 genes encoding the major sugar component of the homopolymeric capsule were up-expressed >2.5-fold, but capsule was still produced in the absence of virAG. Actin tail formation required virAG as well as bimB, bimC and bimE, three previously uncharacterized genes that were activated four-to 15-fold when VirAG was overproduced. Surprisingly, actin polymerization was found to be dispensable for virulence in hamsters. In contrast, genes encoding a T6S system were up-expressed as much as 30-fold and mutations in this T6S gene cluster resulted in strains that were avirulent in hamsters. SDS-PAGE and mass spectrometry demonstrated that BMAA0742 was secreted by the T6S system when virAG was overexpressed. Purified His-tagged BMAA0742 was recognized by glanders antiserum from a horse, a human and mice, indicating that this Hcp-family protein is produced in vivo during infection.

Direct and Indirect Impairment of Human Dendritic Cell Function by VirulentFrancisella tularensisSchu S4

“…Interestingly, an important function of these proteases is the induction of LPS tolerance in macrophages (18,41). Type VI secretion systems have also been identified in Yersinia and Burkholderia species (44,52). While their presence is associated with virulence, the specific effectors and their mechanisms of action on a cellular level have not been defined.…”

Genomic versatility and functional variation between two dominant heterotrophic symbionts of deep-sea Osedax worms

“…Both Osedax symbionts contain pil genes responsible for Type IV pili formation, including pilin subunits, a prepilin peptidase, assembly and retraction ATPases, an inner membrane protein, and a secretin (Supplementary Results;Craig and Li, 2008). Similarly, they possess imp genes that encode Type VI pili formation, as well as the clpB and vrgG genes observed to be necessary for host cell interactions and virulence in many pathogens (Table 3; Supplementary Results; Schlieker et al, 2005;Schell et al, 2007;Schwarz et al, 2010). Neither of the closest free-living relatives, Neptuniibacter caesariensis and Neptunomonas japonica, possess Type VI secretion systems.…”

Structural similarity of tailed phages and pathogenic bacterial secretion systems

“…However, less is known about the organization, function, and mechanism of the T6SS system first discovered by Mekalanos and coworkers in 2006 (3). After their initial report, a number of bioinformatics-based comparative analyses of the T6SS gene clusters between bacterial strains have been made to assess possible function (4)(5)(6)(7)(8)(9)(10). In this issue of PNAS, both Leiman et al (11) and Pell et al (12) use structure-based analysis to demonstrate the existence of a structure/function relationship between the molecular components of T6SS and the tail proteins of bacteriophages T4 (11) and (12).…”