Development of Vaccines Against Burkholderia Pseudomallei

Patel, Nirav; Conejero, Laura; Reynal, Melanie de; Easton, Anna; Bancroft, Gregory J.; Titball, Richard W.

doi:10.3389/fmicb.2011.00198

Cited by 67 publications

(82 citation statements)

References 174 publications

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“…Development of vaccines to prevent naturally acquired infections and to protect from use of the organism as a biological weapon is under way (56)(57)(58). These include live-attenuated, whole-cell killed, subunit, glycoconjugate, outer-membrane vesicle, DNA, and dendritic cell vaccines (56).…”

Section: Therapeutic Approaches Antimicrobial Resistance and Prevenmentioning

confidence: 99%

Burkholderia pseudomallei: Challenges for the Clinical Microbiology Laboratory

et al. 2016

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bMelioidosis is a potentially fatal infection caused by the bacterium Burkholderia pseudomallei. Clinical diagnosis of melioidosis can be challenging since there is no pathognomonic clinical syndrome, and the organism is often misidentified by methods used routinely in clinical laboratories. Although the disease is more prevalent in Thailand and northern Australia, sporadic cases may be encountered in areas where it is not endemic, including the United States. Since the organism is considered a tier 1 select agent according to the Centers for Disease Control and Prevention and the U.S. Department of Agriculture Animal and Plant Health Inspection Service, clinical laboratories must be proficient at rapidly recognizing isolates suspicious for B. pseudomallei, be able to safely perform necessary rule-out tests, and to refer suspect isolates to Laboratory Response Network reference laboratories. In this minireview, we report a case of melioidosis encountered at our institution and discuss the laboratory challenges encountered when dealing with clinical isolates suspicious for B. pseudomallei or clinical specimens from suspected melioidosis cases. CASEA 67-year-old Filipino woman with a previous history of treated tuberculosis, hypertension, type 2 diabetes, coronary artery disease, and complete heart block requiring a pacemaker and drug-eluting stent that was placed 4 months earlier presented to an outside hospital with 2 weeks of progressive left lower quadrant abdominal pain, chills, and subjective fever. She was evaluated in different emergency departments for similar complaints on two occasions in the preceding week, but was discharged home. She was admitted to an outside hospital on this visit and computed tomography (CT) of the abdomen and pelvis with intravenous contrast revealed an 8 by 8 by 8 mm suprarenal saccular aneurysm arising from the posterior aortic wall with surrounding inflammation. Blood cultures drawn in the emergency department grew a Gram-negative rod, which was identified by the Vitek 2 (bioMérieux, Durham NC) as Burkholderia pseudomallei. This identification was confirmed several weeks later by the Centers for Disease Control and Prevention (CDC). Transthoracic echocardiography showed no vegetation. The patient was treated with meropenem 1 g intravenously (i.v.) every 8 hours (q8h). Follow-up CT scans performed 9 days after presentation showed that the mycotic aneurysm had enlarged to 13 by 24 by 20 mm and revealed a second aneurysm of the lateral wall of the aorta measuring 4 by 4 mm.The patient was transferred to our institution for surgical evaluation. On arrival, two sets of blood cultures (BD Bactec FX system; Becton, Dickinson and Company, NJ) were collected. Within 48 h of transfer, the patient underwent surgical excision of the mycotic aneurysm and reconstruction of her aorta using bioprosthetic homografts. During the procedure, the aneurysm was found to have ruptured, with the resulting pseudoaneurysm encased in inflammatory material and purulent fluid. Intraoperative samples from t...

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Section: Therapeutic Approaches Antimicrobial Resistance and Prevenmentioning

confidence: 99%

Burkholderia pseudomallei: Challenges for the Clinical Microbiology Laboratory

et al. 2016

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“…Moreover, liveattenuated vaccines usually confer strong and long-lasting immunity. Several live-attenuated vaccine strains of B. pseudomallei have been tested to date [reviewed by Sarkar-Tyson and Titball (42) and Patel et al (38)]. Most of them are mutants with defects in the intracellular life stages, such as mutations in biosynthetic pathways or type III secretion systems.…”

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confidence: 99%

Role of RelA and SpoT in Burkholderia pseudomallei Virulence and Immunity

et al. 2012

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bBurkholderia pseudomallei is a Gram-negative soil bacterium and the causative agent of melioidosis, a disease of humans and animals. It is also listed as a category B bioterrorism threat agent by the U.S. Centers for Disease Control and Prevention, and there is currently no melioidosis vaccine available. Small modified nucleotides such as the hyperphosphorylated guanosine molecules ppGpp and pppGpp play an important role as signaling molecules in prokaryotes. They mediate a global stress response under starvation conditions and have been implicated in the regulation of virulence and survival factors in many bacterial species. In this study, we created a relA spoT double mutant in B. pseudomallei strain K96243, which lacks (p)ppGpp-synthesizing enzymes, and investigated its phenotype in vitro and in vivo. The B. pseudomallei ⌬relA ⌬spoT mutant displayed a defect in stationary-phase survival and intracellular replication in murine macrophages. Moreover, the mutant was attenuated in the Galleria mellonella insect model and in both acute and chronic mouse models of melioidosis. Vaccination of mice with the ⌬relA ⌬spoT mutant resulted in partial protection against infection with wild-type B. pseudomallei. In summary, (p)ppGpp signaling appears to represent an essential component of the regulatory network governing virulence gene expression and stress adaptation in B. pseudomallei, and the ⌬relA ⌬spoT mutant may be a promising live-attenuated vaccine candidate.

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“…The presence of this capsule facilitates survival as well as spreading to other organs, which can explain the overwhelming septicemia that is common in culture-positive melioidosis patients [64]. Therefore CPS I production is critical to the virulence of B. pseudomallei and further research will enhance the development of preventative strategies for melioidosis since this polysaccharide is one of the components of a B. pseudomallei subunit vaccine [28,65].…”

Section: Resultsmentioning

confidence: 99%

Capsular Polysaccharides Produced by the Bacterial Pathogen Burkholderia pseudomallei

Reckseidler-Zenteno¹

2012

The Complex World of Polysaccharides

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The Complex World of Polysaccharides 132 the weakly virulent B. thailandensis (6.8 x 10 5 CFU) [42]. This demonstrated that SR1015 is severely attenuated for virulence in this animal model of melioidosis and that type I O-PS is a major virulence determinant of B. pseudomallei. We later determined that the type I O-PS was a capsular polysaccharide (CPS I), not an O-PS moiety, which will be discussed below.

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Development of Vaccines Against Burkholderia Pseudomallei

Cited by 67 publications

References 174 publications

Burkholderia pseudomallei: Challenges for the Clinical Microbiology Laboratory

Burkholderia pseudomallei: Challenges for the Clinical Microbiology Laboratory

Role of RelA and SpoT in Burkholderia pseudomallei Virulence and Immunity

Capsular Polysaccharides Produced by the Bacterial Pathogen Burkholderia pseudomallei

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