The contribution of quorum sensing to the pathogenesis of pseudomonas aeruginosa in burn wound infections

Abstract

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes severe infections in burned patients. In this work, we examined the contribution ofthe cell-to-cell communication systems or quorum sensing (QS) systems to the pathogenesis of P aeruginosa infection of burn wounds. For these studies, we used the thermally-injured mouse model and specific mutants that carry deletions in genes encoding specific components of the P aeruginosa QS systems {lasR, rhlR, lasl and rhll). In comparison with their parent strain (PAOl), all mutants displayed decreased lethality. The mutants were defective in their ability to spread systemically throughout the body of the mice. In addition, the lasR (PAO-Rl) and the lasl/rhll (PAO-JP2) mutants were defective in their ability to spread locally within the burned skin at 8 and 16 hours post-bum/infection. The defects in the PAO-JP2 strain were complemented upon the introduction of a plasmid carrying intact lasl and rhll genes. To determine if the defect in PAO-JP2 is due to the loss of one or more of the QScontrolled virulence factors, isogenic mutants that carry deletions in lasA, lasB, lasAAasB, toxA, lasB/toxA or rpoS were examined. With the exception of the rpoS mutant, all mutants were defective in their in vivo virulence. However, none was as severely defective as PAO-JP2. Our attempt to ascertain the role of autoinducers as virulence factors was confounded by the influence of the solvent used to purify them. Host production of cytokines in response to P aeruginosa infection in bum wounds was examined using the Multi-Probe Template/RNase protection assay. The expression of several proinflammatory and hematopoietic cytokines was up-regulated in burned mice infected with PAOl at 40 hours post-bum/infection. In contrast, the expression of most of these cytokines was not enhanced in burned mice infected with PAO-JP2. These results suggest that: (1) the QS systems play an important role in the pathogenesis of P aeruginosa in bum wound infections; (2) their effects may be contributed to by autoinducers or other, yet undefined, QS-controlled factors; and (3) QS may play a role in modulating the host immune system in response to P. aeruginosa.