title: Neutrophil extracellular traps exhibit antibacterial activity against burkholderia pseudomallei and are influenced by bacterial and host factors.
abstract: Burkholderia pseudomallei is the causative pathogen of melioidosis, of which a major predisposing factor is diabetes mellitus. Polymorphonuclear neutrophils (PMNs) kill microbes extracellularly by the release of neutrophil extracellular traps (NETs). PMNs play a key role in the control of melioidosis, but the involvement of NETs in killing of B. pseudomallei remains obscure. Here, we showed that bactericidal NETs were released from human PMNs in response to B. pseudomallei in a dose- and time-dependent manner. B. pseudomallei-induced NET formation required NADPH oxidase activation but not phosphatidylinositol-3 kinase, mitogen-activated protein kinases, or Src family kinase signaling pathways. B. pseudomallei mutants defective in the virulence-associated Bsa type III protein secretion system (T3SS) or capsular polysaccharide I (CPS-I) induced elevated levels of NETs. NET induction by such mutants was associated with increased bacterial killing, phagocytosis, and oxidative burst by PMNs. Taken together the data imply that T3SS and the capsule may play a role in evading the induction of NETs. Importantly, PMNs from diabetic subjects released NETs at a lower level than PMNs from healthy subjects. Modulation of NET formation may therefore be associated with the pathogenesis and control of melioidosis.
authors.affiliation: The Centre for Research & Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Donporn
authors.initials: D
authors.lastname: Riyapa
authors.forename: Surachat
authors.initials: S
authors.lastname: Buddhisa
authors.forename: Sunee
authors.initials: S
authors.lastname: Korbsrisate
authors.forename: Jon
authors.initials: J
authors.lastname: Cuccui
authors.forename: Brendan W
authors.initials: BW
authors.lastname: Wren
authors.forename: Mark P
authors.initials: MP
authors.lastname: Stevens
authors.forename: Manabu
authors.initials: M
authors.lastname: Ato
authors.forename: Ganjana
authors.initials: G
authors.lastname: Lertmemongkolchai
mesh_terms: D000907:Antibodies, Bacterial / Q000032:analysis; D001426:Bacterial Proteins; D016957:Burkholderia pseudomallei / Q000276:immunology* / Q000472:pathogenicity; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D006801:Humans; D008554:Melioidosis / Q000276:immunology*; D050296:Microbial Viability; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis; D016897:Respiratory Burst / Q000276:immunology*; D014774:Virulence; D037521:Virulence Factors
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D037521:Virulence Factors