Evidence for a role of the polysaccharide capsule transport proteins in pertussis pathogenesis.

PLoS One 2014 12;9(12):e115243. Epub 2014 Dec 12.

Department of Microbiology, Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Centre for Life Science #03-05, 28 Medical Drive, Singapore 117597, Singapore.

Polysaccharide (PS) capsules are important virulence determinants for many bacterial pathogens. Bordetella pertussis, the agent of whooping cough, produces a surface associated microcapsule but its role in pertussis pathogenesis remained unknown. Here we showed that the B. pertussis capsule locus is expressed in vivo in murine lungs and that absence of the membrane-associated protein KpsT, involved in the transport of the PS polymers across the envelope, but not the surface-exposed PS capsule itself, affects drastically B. pertussis colonization efficacy in mice. Microarray analysis revealed that absence of KpsT in B. pertussis resulted in global down-regulation of gene expression including key virulence genes regulated by BvgA/S, the master two-component system. Using a BvgS phase-locked mutant, we demonstrated a functional link between KpsT and BvgA/S-mediated signal transduction. Whereas pull-down assays do not support physical interaction between BvgS sensor and any of the capsule locus encoded proteins, absence of KpsT impaired BvgS oligomerization, necessary for BvgS function. Furthermore, complementation studies indicated that instead of KpsT alone, the entire PS capsule transport machinery spanning the cell envelope likely plays a role in BvgS-mediated signal transduction. Our work thus provides the first experimental evidence of a role for a virulence-repressed gene in pertussis pathogenesis.

Download full-text PDF

Source
https://pdfs.semanticscholar.org/8eb7/0dc9c3f5555f88b7850695
Web Search
http://dx.plos.org/10.1371/journal.pone.0115243
Publisher Site
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0115243PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264864PMC
March 2016
4 Reads

Publication Analysis

Top Keywords

pertussis pathogenesis
12
signal transduction
8
absence kpst
8
capsule locus
8
evidence role
8
capsule transport
8
pertussis
7
capsule
5
kpst
5
revealed absence
4
analysis revealed
4
microarray analysis
4
expression including
4
complementation studies
4
kpst pertussis
4
function complementation
4
bvgs function
4
down-regulation gene
4
mice microarray
4
global down-regulation
4

References

(Supplied by CrossRef)
Polysaccharide capsule-mediated resistance to opsonophagocytosis in Klebsiella pneumoniae
P Domenico et al.
Infect Immun 1994
Bacterial evasion of antimicrobial peptides by biofilm formation
M Otto et al.
Curr Top Microbiol Immunol 2006
What is new in pertussis?
ES Bamberger et al.
Eur J Pediatr 2008
Improving pertussis vaccination
GA Berbers et al.
Hum Vaccin 2009

Similar Publications