title: Superoxide dismutase C is required for intracellular survival and virulence of Burkholderia pseudomallei.
abstract: Burkholderia pseudomallei is an intracellular pathogen and the causative agent of melioidosis, a life-threatening disease of humans. Within host cells, superoxide is an important mediator of pathogen killing. In this study, we have identified the B. pseudomallei K96243 sodC gene, shown that it has superoxide dismutase activity, and constructed an allelic deletion mutant of this gene. Compared with the wild-type, the mutant was more sensitive to killing by extracellular superoxide, but not to superoxide generated intracellularly. The sodC mutant showed a markedly decreased survival in J774A.1 mouse macrophages, and reduced numbers of bacteria were recovered from human polymorphonuclear neutrophils (PMNs) when compared with the wild-type. The numbers of wild-type or mutant bacteria recovered from human diabetic neutrophils were significantly lower than from normal human neutrophils. The sodC mutant was attenuated in BALB/c mice. Our results indicate that SodC plays a key role in the virulence of B. pseudomallei, but that diabetics are not more susceptible to infection because of a reduced ability of PMNs to kill by superoxide.
authors.affiliation: Department of Microbiology and Immunology, Mahidol University, Rajvithi Road, Bangkok 10400, Thailand.|College of Life and Environmental Sciences, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter EX4 4QD, UK.
authors.forename: Muthita
authors.initials: M
authors.lastname: Vanaporn
authors.affiliation: Health Protection Agency, Porton Down, Salisbury SP4 0JG, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Wand
authors.affiliation: College of Life and Environmental Sciences, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter EX4 4QD, UK.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Michell
authors.affiliation: Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK.
authors.forename: Mitali
authors.initials: M
authors.lastname: Sarkar-Tyson
authors.affiliation: Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Ireland
authors.affiliation: Genetic Chemistry Inc., 200 Page Mill Road, Palo Alto, CA 94306, USA.
authors.forename: Stan
authors.initials: S
authors.lastname: Goldman
authors.affiliation: The Center for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Chidchamai
authors.initials: C
authors.lastname: Kewcharoenwong
authors.affiliation: The Center for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Darawan
authors.initials: D
authors.lastname: Rinchai
authors.affiliation: The Center for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Ganjana
authors.initials: G
authors.lastname: Lertmemongkolchai
authors.affiliation: College of Life and Environmental Sciences, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter EX4 4QD, UK.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Titball
mesh_terms: D000818:Animals; D016957:Burkholderia pseudomallei / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008554:Melioidosis / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D012376:Rodent Diseases / Q000382:microbiology / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D037521:Virulence Factors; D013482:Superoxide Dismutase