Immunospecific Responses to Bacterial Elongation Factor Tu during Burkholderia Infection and Immunization

Wildaliz Nieves,Kerstin Höner zu Bentrup,Chad J. Roy,Saja Asakrah,Lisa A. Morici,Julie Heang,Ramy K. Aziz

doi:10.1371/journal.pone.0014361

Wildaliz Nieves, Kerstin Höner zu Bentrup + Show 5 more

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https://doi.org/10.1371/journal.pone.0014361

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Journal: PloS one	Publication Date: Dec 17, 2010
Citations: 81	License type: CC BY 4.0

Affiliation: Tulane University

Abstract

Burkholderia pseudomallei is the etiological agent of melioidosis, a disease endemic in parts of Southeast Asia and Northern Australia. Currently there is no licensed vaccine against infection with this biological threat agent. In this study, we employed an immunoproteomic approach and identified bacterial Elongation factor-Tu (EF-Tu) as a potential vaccine antigen. EF-Tu is membrane-associated, secreted in outer membrane vesicles (OMVs), and immunogenic during Burkholderia infection in the murine model of melioidosis. Active immunization with EF-Tu induced antigen-specific antibody and cell-mediated immune responses in mice. Mucosal immunization with EF-Tu also reduced lung bacterial loads in mice challenged with aerosolized B. thailandensis. Our data support the utility of EF-Tu as a novel vaccine immunogen against bacterial infection.

Highlights

The bacterium Burkholderia pseudomallei is a Gram-negative, facultative intracellular bacillus and the causative agent of melioidosis, a serious emerging disease responsible for significant morbidity and mortality in Southeast Asia and Northern Australia [1]
Pooled antisera from B. malleiimmunized rabbits was used to probe a B. thailandensis whole cell lysate that was separated by 2D-gel electrophoresis (Figure 1A)
We hypothesized that proteins shared by B. mallei, B. pseudomallei, and B. thailandensis could be detected by this approach due to the extensive homology between the three species [19]

Summary

Introduction

The bacterium Burkholderia pseudomallei is a Gram-negative, facultative intracellular bacillus and the causative agent of melioidosis, a serious emerging disease responsible for significant morbidity and mortality in Southeast Asia and Northern Australia [1]. Mortality rates associated with severe B. pseudomallei infection approach 50% and can reach 80–95% in patients with septic shock despite antibiotic treatment [3,4]. This is partially due to the innate antimicrobial resistance of B. pseudomallei as well as the intracellular niche of the organism [1,5]. Preventive measures such as active immunization are needed to reduce the morbidity and mortality associated with B. pseudomallei infection

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Conclusion