Quorum Sensing: A transcriptional Regulatory System Involved in the Pathogenicity of Burkholderia mallei

Abstract

Numerous gram-negative bacterial pathogens regulate virulence factor expression by using a cell density mechanism termed quorum sensing (QS). An in silico analysis of the Burkholderia mallei ATCC 23344 genome revealed that it encodes at least two luxI and four luxR homologues. Using mass spectrometry, we showed that wild-type B. mallei produces the signaling molecules N-octanoyl-homoserine lactone and N-decanoyl-homoserine lactone. To determine if QS is involved in the virulence of B. mallei, we generated mutations in each putative luxIR homologue and tested the pathogenicities of the derivative strains in aerosol BALB/c mouse and intraperitoneal hamster models. Disruption of the B. mallei QS alleles, especially in RJ16 (bmaII) and RJ17 (bmaI3), which are luxI mutants, significantly reduced virulence, as indicated by the survival of mice who were aerosolized with 10(4) CFU (10 50% lethal doses LD50s). For the B. mallei transcriptional regulator mutants (luxR homologues), mutation of the bmaR5 allele resulted in the most pronounced decrease in virulence, with 100% of the challenged animals surviving a dose of 10 LD50s. Using a Syrian hamster intraperitoneal model of infection, we determined the LD50s for wild-type B. mallei and each QS mutant. An increase in the relative LD50 was found for RJ16 (bmaI1) (>967 CFU), RJ17 (bmaI3) (115 CFU), and RJ20 (bmaR5) (151 CFU) compared to wild-type B. mallei (<13 CFU). These findings demonstrate that B. mallei carries multiple luxIR homologues that either directly or indirectly regulate the biosynthesis of an essential virulence factor(s) that contributes to the pathogenicity of B. mallei in vivo.

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Document Details

Document Type
Technical Report
Publication Date
Nov 01, 2004
Accession Number
ADA429432

Entities

People

  • David Deshazer
  • Harry B. Hines
  • Jeffrey A. Jeddeloh
  • Ricky L. Ulrich

Organizations

  • United States Army Medical Research Institute of Infectious Diseases

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Anabolism
  • Bacteria
  • Biological Toxins
  • Carrier Proteins
  • Cells
  • Homoserine
  • Infection
  • Mass Spectrometry
  • Metabolism
  • Microorganisms
  • Molecules
  • Pathogenic Bacteria
  • Rodents
  • Spectrometry
  • United States
  • Wound Infections

Fields of Study

  • Biology

Readers

  • Microbial Pathology