The serine protease inhibitor Ecotin is required for full virulence of Burkholderia pseudomallei.
Burkholderia pseudomallei is a Gram negative soil saprophyte that causes the disease melioidosis where clinical symptoms can vary from localised infection to pneumonia and septic shock. Ecotin is a potent periplasmic serine protease inhibitor first identified in Escherichia coli. Ecotin, although present in only a small subset of genera, can inhibit a broad range of serine proteases including those typically associated with the innate immune system such as neutrophil elastase and cathepsin G. An Ecotin orthologue identified in B. pseudomallei was recombinantly expressed and found to inhibit elastase. To study the role of Ecotin in B. pseudomallei virulence an in-frame unmarked deletion mutant was created. Infection of a murine macrophages-like cell line revealed Ecotin was necessary for the early stages of colonisation allowing replication following cell entry. Attenuation of the Δeco mutant strain in the murine model of melioidosis further supported Ecotin as a virulence factor of B. pseudomallei.
Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK. Electronic address: pmireland@dstl.gov.uk.
Philip M
PM
Ireland
Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
Laura
L
Marshall
Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
Isobel
I
Norville
Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK; Pathology & Laboratory Medicine M504, University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009, Australia.
Mitali
M
Sarkar-Tyson
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D016957:Burkholderia pseudomallei / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D005260:Female; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008554:Melioidosis / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
D001426:Bacterial Proteins; D015842:Serine Proteinase Inhibitors
Burkholderia pseudomallei; Ecotin; Macrophage; Serine protease; Virulence