Evidence for a Role of the Polysaccharide Capsule Transport Proteins in Pertussis Pathogenesis

Abstract

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.

Transcriptional profiling of human macrophages during infection withBordetella pertussis

“…In line with these observations, the expression of virulence repressed gene vrg6 was induced during the infection. Of note, increased expression of vrg6 gene was observed also in B. pertussis cells recovered from lungs of intranasally infected mice [74]. While this gene was one of the first described virulence repressed genes in B. pertussis [75], its cellular function remained unclear.…”

Widespread Antibiotic, Biocide, and Metal Resistance in Microbial Communities Inhabiting a Municipal Waste Environment and Anthropogenically Impacted River

“…Some shared modules are rare in their distribution among prokaryotes, including pathways for polyamine biosynthesis (M00134), vitamin and cofactor biosynthesis (M00124 and M00121), drug efflux (M00720), as well as transport systems for biotin (M00581), capsular polysaccharide (M00249), rhamnose (M00220), and l -arabinose or lactose (M00199). These rare modules have been shown to contribute to stress tolerance, viability, or virulence in some microbes ( 23 – 25 ). Benzoate degradation (M00551) is a restricted, rare pathway that is also shared by MAGs of the leachate and river metagenomes.…”

The Bordetella bronchiseptica nic locus encodes a nicotinic acid degradation pathway and the 6‐hydroxynicotinate‐responsive regulator BpsR

“…The cellular benefit or function of the Bordetella modulation response is unknown although the Bvg− phase is thought to be important for survival outside of a host or for transmission between hosts (Cotter and Miller, ). However, recent studies indicate that Bordetella cells do experience Bvg− conditions in vivo (Mason et al ., ; Hoo et al ., , Dewan et al ., ). In another study, investigators identified B .…”

“…The cellular benefit or function of the Bordetella modulation response is unknown although the Bvg2 phase is thought to be important for survival outside of a host or for transmission between hosts (Cotter and Miller, 1997). However, recent studies indicate that Bordetella cells do experience Bvg2 conditions in vivo (Mason et al, 2013;Hoo et al, 2014, Dewan et al, 2017. In another study, investigators identified B. bronchiseptica brtA, a lapA ortholog, and demonstrated it was a Bvg2 phase gene involved in biofilm formation and expressed in infected rat trachea (Nishikawa et al, 2016).…”