A proteasome inhibitor produced by Burkholderia pseudomallei modulates intracellular growth.
The NRPS/PKS cluster encodes the enzymes necessary for glidobactin synthesis it is partially conserved in various members of the Burkholderia genus including B. pseudomallei. In this study we have shown that the insertional inactivation or deletion of glbC in this cluster in B. pseudomallei could reduce the ability of the bacterium to survive or grow in murine macrophages or in human neutrophils. Exogenously added proteasome inhibitors were able to chemically complement the mutation. The insertional inactivation or deletion of glbC increased virulence in an acute model of infection in Balb/c or C57BL/6 mice but virulence in a chronic model of infection was similar to that of the wild type. Our findings contrast with the previous finding that inactivation of the glb gene cluster in B. pseudomallei strain 1026b resulted in marked attenuation, and provides evidence of differential roles for some genes in virulence of different strains of B. pseudomallei.
College of Life and Environmental Sciences, University of Exeter, Exeter, Devon, EX4 4QD, UK.
Sariqa
S
Wagley
Department of Microbiology and Immunology, Mahidol University, Rajvithi Road, Bangkok, 10400, Thailand.
Muthita
M
Vanaporn
The Cellular and Molecular Immunology Unit, The Center for Research and Development of Medical Diagnostic Laboratories (CMDL), Faculty of Associated Medical Sciences, Khon Kaen University, Thailand.
Darawan
D
Rinchai
Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, UK.
Laura
L
Conejero
The Cellular and Molecular Immunology Unit, The Center for Research and Development of Medical Diagnostic Laboratories (CMDL), Faculty of Associated Medical Sciences, Khon Kaen University, Thailand.
Ganjana
G
Lertmemongkolchai
Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, UK.
Gregory J
GJ
Bancroft
College of Life and Environmental Sciences, University of Exeter, Exeter, Devon, EX4 4QD, UK. Electronic address: r.w.titball@exeter.ac.uk.
Richard W
RW
Titball
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D016957:Burkholderia pseudomallei / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism* / Q000472:pathogenicity; D002460:Cell Line; D004269:DNA, Bacterial / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000235:genetics; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000187:drug effects / Q000235:genetics; D008264:Macrophages / Q000382:microbiology; D008554:Melioidosis / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D005810:Multigene Family / Q000235:genetics; D016254:Mutagenesis, Insertional / Q000379:methods; D009154:Mutation; D009504:Neutrophils / Q000382:microbiology; D010453:Peptide Synthases / Q000235:genetics; D048630:Polyketide Synthases / Q000235:genetics; D061988:Proteasome Inhibitors / Q000378:metabolism*; D017384:Sequence Deletion; D013534:Survival; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics*
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D061988:Proteasome Inhibitors; D037521:Virulence Factors; C057880:glidobactin C; D048630:Polyketide Synthases; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase; D008239:Lysine
Burkholderia; Melioidosis; Proteasome