A Novel Sensor Kinase Is Required for Bordetella bronchiseptica To Colonize the Lower Respiratory Tract

Abstract

Bacterial virulence is influenced by the activity of two-component regulator systems (TCSs), which consist of membrane-bound sensor kinases that allow bacteria to sense the external environment and cytoplasmic, DNA-binding response regulator proteins that control appropriate gene expression. Respiratory pathogens of the Bordetella genus require the well-studied TCS BvgAS to control the expression of many genes required for colonization of the mammalian respiratory tract. Here we describe the identification of a novel gene in Bordetella bronchiseptica, plrS, the product of which shares sequence homology to several NtrY-family sensor kinases and is required for B. bronchiseptica to colonize and persist in the lower, but not upper, respiratory tract in rats and mice. The plrS gene is located immediately 5 to and presumably cotranscribed with a gene encoding a putative response regulator, supporting the idea that PlrS and the product of the downstream gene may compose a TCS. Consistent with this hypothesis, the PlrS-dependent colonization phenotype requires a conserved histidine that serves as the site of autophosphorylation in other sensor kinases, and in strains lacking plrS, the production and/or cellular localization of several immune-recognized proteins is altered in comparison to that in the wild-type strain. Because plrS is required for colonization and persistence only in the lower respiratory tract, a site where innate and adaptive immune mechanisms actively target infectious agents, we hypothesize that its role may be to allow Bordetella to resist the host immune response.

The NtrY/X two‐component system of Brucella spp. acts as a redox sensor and regulates the expression of nitrogen respiration enzymes

“…The insertion of a transposon in the ntrY gene affects the intracellular survival of B. suis in an in vitro human macrophage infection model (Foulongne et al ., 2000). A mutation in the ntrY homologous (named plrS ) of the respiratory pathogen B. bronchiseptica affects bacterial colonization and persistence in the lower respiratory tract of infected rats (Kaut et al ., 2011). However, the signal sensed by NtrY and its mechanism of action are largely unknown.…”

Bordetella PlrSR regulatory system controls BvgAS activity and virulence in the lower respiratory tract

“…Taken together, these data suggest that PlrS, via PlrR, exerts its effects on BvgAS activity posttranscriptionally. ΔbvgS mutants from the LRT of mice (13,18), we hypothesized that PlrS may influence BvgAS activity within the host. To test this hypothesis, we used two reporter systems developed in our laboratory.…”

“…In a survey of putative TCSs in B. bronchiseptica, we discovered a gene (BB0264) predicted to encode an NtrY-like sensor kinase that is essential for B. bronchiseptica to colonize the trachea of rats following low-dose, low-volume intranasal inoculation and to persist in the lungs of mice following high-dose, large-volume intranasal inoculation (18). We named BB0264 plrS, for persistence in the lower respiratory tract (LRT) sensor.…”

Porcine Respiratory Disease Complex and Biofilms

“…Bordetella bronchiseptica is a Gram negative bacteria pathogen of respiratory tract and can infect a wide range of mammals [82][83]. B. bronchiseptica is also being increasingly isolated from humans, mainly from immunocompromised patients [84].…”

“…It is considered one of the mains causative agents of atrophic rhinitis in pigs [85] along with P. multocida [86]. Infections with this microorganism are transmitted by aerosol and bacteria can be localized invading the epithelial cells of the respiratory tract [83], where the damage to the respiratory tract is fundamentally caused by dermonecrotic toxins [86]. Several recent reports have demonstrated the isolation of B. bronchiseptica from cystic fibrosis (CF) patients [87].…”