Abstract
Burkholderia pseudomallei is resistant to a diverse group of antimicrobials including third generation cephalosporins whilst quinolones and aminoglycosides have no reliable effect. As therapeutic options are limited, development of more effective forms of immunotherapy is vital to avoid a fatal outcome. In an earlier study, we reported on the B. pseudomallei serine MprA protease, which is relatively stable over a wide pH and temperature range and digests physiological proteins. The present study was carried out to evaluate the immunogenicity and protective efficacy of the MprA as a potential vaccine candidate. In BALB/c mice immunized with recombinant MprA protease (smBpF4), a significantly high IgG titer was detectable. Isotyping studies revealed that the smBpF4-specific antibodies produced were predominantly IgG1, proposing that immunization with smBpF4 triggered a Th2 immune response. Mice were immunized with smBpF4 and subsequently challenged with B. pseudomallei via the intraperitoneal route. Whilst control mice succumbed to the infection by day 9, smBpF4-immunized mice were protected against the lethal challenge and survived beyond 25 days post-infection. In conclusion, MprA is immunogenic in melioidosis patients whilst also eliciting a strong immune response upon bacterial challenge in mice and presents itself as a potential vaccine candidate for the treatment of melioidosis.
Highlights
Burkholderia pseudomallei is the Gram negative etiological agent for melioidosis, a potentially acute fulminating disease in humans and animals in Southeast Asia and Northern Australia (Cheng and Currie, 2005; Peacock, 2006)
B. pseudomallei PROTEASES ARE IMPLICATED IN C. elegans KILLING The prevalent view on the mode of action of extracellular proteases toward nematodes is that these proteases participate in cuticle penetration
To determine if B. pseudomallei proteases contribute to killing of C. elegans, a combination of serine protease inhibitors was added to the B. pseudomallei culture to inhibit the secreted proteases
Summary
Burkholderia pseudomallei is the Gram negative etiological agent for melioidosis, a potentially acute fulminating disease in humans and animals in Southeast Asia and Northern Australia (Cheng and Currie, 2005; Peacock, 2006). In areas where this bacterium is endemic, infection by B. pseudomallei has been estimated to be responsible for 20–30% mortality due to septicaemia and 40% of sepsis-related mortality (Wiersinga et al, 2006). The use of protection-eliciting pathogen proteins, for example virulence factors, is looked upon as an alternative and viable approach as previously demonstrated with the caseinolytic protease of Streptococcus pneumoniae (Cao et al, 2009), parasite cysteine proteases (Jorgensen and Buchmann, 2011), cytotoxic serine protease of Vibrio harveyi (Cheng et al, 2010), outer membrane proteins of Haemophilus parasuis (Yuan et al, 2011), and outer membrane secretin PilQ of Neisseria meningitidis (Haghi et al, 2012)
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