The CepIR quorum-sensing system contributes to the virulence of Burkholderia cenocepacia respiratory infections

Abstract

The cepIR genes encode an N-acyl homoserine lactone (AHL)-dependent quorum-sensing system consisting of an AHL synthase that directs the synthesis of N-octanoyl-L-homoserine lactone (OHL) and N-hexanoyl-L-homoserine lactone and a transcriptional regulator. The virulence of cepIR mutants was examined in two animal models. Rats were infected with agar beads containing Burkholderia cenocepacia K56-2, K56-I2 (cepI : : Tp r ) or K56-R2 (cepR : : Tn5-OT182). At 10 days post-infection, the extent of lung histopathological changes was significantly lower in lungs infected with K56-I2 or K56-R2 compared to the parent strain. Intranasal infections were performed in Cftr ("/") mice and their wild-type siblings. K56-2 was more virulent in both groups of mice. K56-I2 was the least virulent strain and was not invasive in the Cftr ("/") mice. OHL was readily detected in lung homogenates from Cftr ("/") mice infected with K56-2 but was only detected at levels slightly above background in a few mice infected with K56-I2. Lung homogenates from mice infected with K56-2 had significantly higher levels of the inflammatory mediators murine macrophage inflammatory protein-2, KC/N51, interleukin-1b and interleukin-6 than those from K56-I2-infected animals. These studies indicate that a functional CepIR quorum-sensing system contributes to the severity of B. cenocepacia infections. A zinc metalloprotease gene (zmpA) was shown to be regulated by CepR and may be one of the factors that accounts for the difference in virulence between the cepI mutant and the parent strain.

Future research trends in the major chemical language of bacteria

“…CepI/R CciI/R C6-HSL, C8-HSL Virulence functions and biofilm formation (Malott et al, 2005;Sokol et al, 2003) Erwinia carotovora…”

Genome-wide analysis of DNA repeats in Burkholderia cenocepacia J2315 identifies a novel adhesin-like gene unique to epidemic-associated strains of the ET-12 lineage

“…They have the capacity of spreading between patients and lead determined (Holden et al, 2009). Although the pathogenesis of Bcc is not well understood, a few virulence factors, such as two quorum-sensing systems (Sokol et al, 2003), iron acquisition via siderophore production (Visser et al, 2004), exopolysaccharide synthesis (Moreira et al, 2003) and a type III secretion system (Tomich et al, 2003), have been identified.…”

Quorum Sensing: a Transcriptional Regulatory System Involved in the Pathogenicity of Burkholderia mallei

“…For human and plant pathogens, AHL-based communication systems allow a microbial community to strategically induce or repress expression of genes, specifically alleles encoding putative virulence factors, in response to environmental stimuli. Several reports have identified functional QS systems in various Burkholderia species and have shown that these bacterial communication networks both positively and negatively regulate numerous extracellular virulence factors in addition to contributing to animal pathogenicity (B. cepacia) (1,3,20,21,31,34,36).…”

“…Collectively, these Burkholderia QS networks have been shown to both positively and negatively regulate various cellular processes, including AHL and protease production, siderophore biosynthesis, biofilm formation, lipase and betahemolytic activities, swarming and twitching motilities, and substrate utilization (18,20,21,32,35,36). Furthermore, disruption of these cell signaling systems has been shown to reduce the pathogenicity of B. cepacia and Burkholderia pseudomallei in murine and hamster models of infection (1,31,34,36).…”