title: Role of quorum sensing in the pathogenicity of Burkholderia pseudomallei.
abstract: Burkholderia pseudomallei is the causative agent of human and animal melioidosis. The role of quorum sensing (QS) in the in vivo pathogenicity of B. pseudomallei via inhalational exposure of BALB/c mice and intraperitoneal challenge of Syrian hamsters has not been reported. This investigation demonstrates that B. pseudomallei encodes a minimum of three luxI and five luxR homologues that are involved in animal pathogenicity. Mass spectrometry analysis of culture supernatants revealed that wild-type B. pseudomallei and the luxI mutants synthesized numerous signalling molecules, including N-octanoyl-homoserine lactone, N-decanoyl-homoserine lactone, N-(3-hydroxyoctanoyl)-L-homoserine lactone, N-(3-hydroxydecanoyl)-L-homoserine lactone and N-(3-oxotetradecanoyl)-L-homoserine lactone, which was further confirmed by heterologous expression of the B. pseudomallei luxI alleles in Escherichia coli. Mutagenesis of the B. pseudomallei QS system increased the time to death and reduced organ colonization of aerosolized BALB/c mice. Further, intraperitoneal challenge of Syrian hamsters with the B. pseudomallei QS mutants resulted in a significant increase in the LD50. Using semi-quantitative plate assays, preliminary analysis suggests that QS does not affect lipase, protease and phospholipase C biosynthesis/secretion in B. pseudomallei. The findings of the investigation demonstrate that B. pseudomallei encodes multiple luxIR genes, and disruption of the QS alleles reduces animal pathogenicity, but does not affect exoproduct secretion.
authors.affiliation: Bacteriology Division1 and Toxinology/Aerobiology Division2, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, MD 21702-5011, USA 3Microbiology, Dstl, CBS Porton Down, Salisbury SP4 0JQ, UK 4Orion Genomics, Center for Emerging Technologies, 4041 Forest Park, St. Louis, MO 63108, USA.
authors.forename: Ricky L
authors.initials: RL
authors.lastname: Ulrich
authors.affiliation: Bacteriology Division1 and Toxinology/Aerobiology Division2, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, MD 21702-5011, USA 3Microbiology, Dstl, CBS Porton Down, Salisbury SP4 0JQ, UK 4Orion Genomics, Center for Emerging Technologies, 4041 Forest Park, St. Louis, MO 63108, USA.
authors.forename: David
authors.initials: D
authors.lastname: DeShazer
authors.affiliation: Bacteriology Division1 and Toxinology/Aerobiology Division2, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, MD 21702-5011, USA 3Microbiology, Dstl, CBS Porton Down, Salisbury SP4 0JQ, UK 4Orion Genomics, Center for Emerging Technologies, 4041 Forest Park, St. Louis, MO 63108, USA.
authors.forename: Ernst E
authors.initials: EE
authors.lastname: Brueggemann
authors.affiliation: Bacteriology Division1 and Toxinology/Aerobiology Division2, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, MD 21702-5011, USA 3Microbiology, Dstl, CBS Porton Down, Salisbury SP4 0JQ, UK 4Orion Genomics, Center for Emerging Technologies, 4041 Forest Park, St. Louis, MO 63108, USA.
authors.forename: Harry B
authors.initials: HB
authors.lastname: Hines
authors.affiliation: Bacteriology Division1 and Toxinology/Aerobiology Division2, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, MD 21702-5011, USA 3Microbiology, Dstl, CBS Porton Down, Salisbury SP4 0JQ, UK 4Orion Genomics, Center for Emerging Technologies, 4041 Forest Park, St. Louis, MO 63108, USA.
authors.forename: Petra C
authors.initials: PC
authors.lastname: Oyston
authors.affiliation: Bacteriology Division1 and Toxinology/Aerobiology Division2, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, MD 21702-5011, USA 3Microbiology, Dstl, CBS Porton Down, Salisbury SP4 0JQ, UK 4Orion Genomics, Center for Emerging Technologies, 4041 Forest Park, St. Louis, MO 63108, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Jeddeloh
mesh_terms: D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D016957:Burkholderia pseudomallei / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D015169:Colony Count, Microbial; D006224:Cricetinae; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics / Q000502:physiology*; D005798:Genes, Bacterial; D006714:Homoserine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D019570:Inhalation Exposure; D007783:Lactones; D007928:Lethal Dose 50; D008049:Lipase / Q000032:analysis; D008554:Melioidosis / Q000382:microbiology* / Q000473:pathology; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D010447:Peptide Hydrolases / Q000032:analysis; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D010738:Type C Phospholipases / Q000032:analysis
chemical_list: D001426:Bacterial Proteins; D007783:Lactones; C085427:LuxI protein, Bacteria; C091088:N-octanoylhomoserine lactone; D011994:Recombinant Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C064778:LuxR autoinducer binding proteins; D006714:Homoserine; D008049:Lipase; D010738:Type C Phospholipases; D010447:Peptide Hydrolases