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

Abstract

ThecepIRgenes encode anN-acyl homoserine lactone (AHL)-dependent quorum-sensing system consisting of an AHL synthase that directs the synthesis ofN-octanoyl-l-homoserine lactone (ohl) andn-hexanoyl-l-homoserine lactone and a transcriptional regulator. The virulence ofcepIRmutants was examined in two animal models. Rats were infected with agar beads containingBurkholderia cenocepaciaK56-2, K56-I2 (cepI : : Tpr) 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 inCftr(−/−)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 theCftr(−/−)mice. OHL was readily detected in lung homogenates fromCftr(−/−)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-1βand interleukin-6 than those from K56-I2-infected animals. These studies indicate that a functional CepIR quorum-sensing system contributes to the severity ofB. cenocepaciainfections. 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 thecepImutant and the parent strain.