The genus Burkholderia consists of diverse species which includes both "friends" and "foes." Some of the "friendly" Burkholderia spp. are extensively used in the biotechnological and agricultural industry for bioremediation and biocontrol. However, several members of the genus including B. pseudomallei, B. mallei, and B. cepacia, are known to cause fatal disease in both humans and animals. B. pseudomallei and B. mallei are the causative agents of melioidosis and glanders, respectively, while B. cepacia infection is lethal to cystic fibrosis (CF) patients. Due to the high rate of infectivity and intrinsic resistance to many commonly used antibiotics, together with high mortality rate, B. mallei and B. pseudomallei are considered to be potential biological warfare agents. Treatments of the infections caused by these bacteria are often unsuccessful with frequent relapse of the infection. Thus, we are at a crucial stage of the need for Burkholderia vaccines. Although the search for a prophylactic therapy candidate continues, to date development of vaccines has not advanced beyond research to human clinical trials. In this article, we review the current research on development of safe vaccines with high efficacy against B. pseudomallei, B. mallei, and B. cepacia. It can be concluded that further research will enable elucidation of the potential benefits and risks of Burkholderia vaccines.
At present, very little is known about how Burkholderia pseudomallei (B. pseudomallei) interacts with its host to elicit melioidosis symptoms. We established a murine acute-phase melioidosis model and used DNA microarray technology to investigate the global host/pathogen interaction. We compared the transcriptome of infected liver and spleen with uninfected tissues over an infection period of 42 hr to identify genes whose expression is altered in response to an acute infection.
Burkholderia pseudomallei infection of the central nervous system (CNS) is rare with less than 50 cases reported over the last 30 years. The retrospective melioidosis study at University Malaya Medical Centre has documented three cases of CNS melioidosis out of more than 160 cases of melioidosis since 1978. There were two patients with brain abscess and one with spinal epidural abscess. The predisposing factors were: one patient was an aboriginal farmer and the other two were diabetic. Their age ranged from 17 to 45 years. Prominent neurological features were limb weakness, cranial nerve palsy (6th and 7th) and visual disturbance. CT brain scan and MRI spine showed abscess formation, subdural collection, and spinal epidural collection, osteomyelitis of vertebra and occipital bone and also sagital sinus thrombosis. All these patients underwent surgical drainage leading to bacteriological diagnosis as well as appropriate long-term antibiotic therapy. All had good recovery at 6 months after completion of treatment.
Burkholderia pseudomallei is a Gram-negative saprophytic soil bacterium, which is the etiologic agent of melioidosis, a severe and fatal infectious disease occurring in human and animals. Distinct clinical and animal isolates have been shown to exhibit differences in phenotypic trait such as growth rate, colony morphology, antimicrobial resistance, and virulence. This study was carried out to gain insight into the intrinsic differences between 4 clinical and 6 animal B. pseudomallei isolates from Malaysia. The 16S rRNA-encoding genes from these 10 isolates of B. pseudomallei were sequenced to confirm the identity of these isolates along with the avirulent Burkholderia thailandensis. The nucleotide sequences indicated that the 16S rRNA-encoding genes among the 10 B. pseudomallei isolates were identical to each other. However, the nucleotide sequence differences in the 16S rRNA-encoding genes appeared to be B. pseudomallei and B. thailandensis specific. The growth rate of all B. pseudomallei isolates was determined by generating growth curves at 37 degrees C for 72 h. The isolates were found to differ in growth rates with doubling time varying from 1.5 to 2.3 h. In addition, the B. pseudomallei isolates exhibited considerable variation in colony morphology when grown on Ashdown media, brain-heart infusion agar, and Luria-Bertani agar over 9 days of observation. Antimicrobial susceptibility tests indicated that 80% of the isolates examined were Amp(R) Cb(R) Kn(R) Gm(R) Chl(S) Te(S). Virulence of the B. pseudomallei clinical and animal isolates was evaluated in B. pseudomallei-susceptible BALB/c mice. Most of the clinical isolates were highly virulent. However, virulence did not correlate with isolate origin since 2 of the animal isolates were also highly virulent.
The disease melioidosis, caused by the soil bacteria Burkholderia pseudomallei, often manifests as acute septicemia with high fatality. Glycogen synthase kinase-3β (GSK3β) plays a key role during the inflammatory response induced by bacteria. We used a murine model of acute melioidosis to investigate the effects of LiCl, a GSK3 inhibitor on experimental animal survivability as well as TNF-α, IL-1β, IFN-γ, IL-10 and IL-1Ra cytokine levels in blood, lung, liver and spleen of B. pseudomallei-infected mice. Our results showed that administration of 100 μg/g LiCl improved survivability of mice infected with 5 X LD50 of B. pseudomallei. Bacterial counts in spleen, liver and lungs of infected mice administered with LiCl were lower than non-treated controls. Our data also revealed that GSK3β is phosphorylated in the spleen, liver and lung of animals infected with B. pseudomallei. However in infected animals administered with LiCl, higher levels of pGSK3 were detected in the organs. Levels of proinflammatory cytokines (TNF-α, IL-1β and IFN-γ) and anti-inflammatory cytokines (IL-10 and IL-1Ra) in sera and organs tested were elevated significantly following B. pseudomallei infection. With GSK3β inhibition, pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β) were significantly decreased in all the samples tested whilst the levels of anti-inflammatory cytokines, IL-10 (spleen and lung) and IL-1Ra (spleen, liver and sera) were further elevated. This study represents the first report implicating GSK3β in the modulation of cytokine production during B. pseudomallei infection thus reiterating the important role of GSK3β in the inflammatory response caused by bacterial pathogens.
Burkholderia pseudomallei, the etiological agent for melioidosis, is known to secrete a type III secretion system (TTSS) protein into the host's internal milieu. One of the TTSS effector protein, BipC, has been shown to play an important role in the B. pseudomallei pathogenesis. To identify the host response profile that was directly or indirectly regulated by this protein, genome-wide transcriptome approach was used to examine the gene expression profiles of infected mice. The transcriptome analysis of the liver and spleen revealed that a total of approximately 1,000 genes were transcriptionally affected by BipC. Genes involved in bacterial invasion, regulation of actin cytoskeleton, and MAPK signalling pathway were over-expressed and may be specifically regulated by BipC in vivo. These results suggest that BipC mainly targets pathways related to the cellular processes which could modulate the cellular trafficking processes. The host transcriptional response exhibited remarkable differences with and without the presence of the BipC protein. Overall, the detailed picture of this study provides new insights that BipC may have evolved to efficiently manipulate host-cell pathways which is crucial in the intracellular lifecycle of B. pseudomallei.
Melioidosis is an infectious disease that is initiated by a bacteria recognized as Burkholderia pseudomallei. Despite the high fatality rate from melioidosis, there is a minimal published study about the disease in Malaysia.This study aimed to identify the prognostic factors of mortality among melioidosis patients in northern Malaysia.All inpatient patients who were admitted to Hospital Sultanah Bahiyah, Kedah and Hospital Tuanku Fauziah, Perlis with culture-confirmed melioidosis during the period 2014 to 2017 were included in the study. The study retrospectively collected 510 melioidosis patients from the Melioidosis Registry. Hazard ratio (HR) used in advanced multiple Cox regression was used to obtain the final model of prognostic factors of melioidosis. The analysis was performed using STATA/SE 14.0 for Windows software.From the results, among the admitted patients, 50.1% died at the hospital. The mean age for those who died was 55 years old, and they were mostly male. The most common underlying disease was diabetes mellitus (69.8%), followed by hypertension (32.7%). The majority of cases (86.8%) were bacteremic. The final Cox model identified 5 prognostic factors of mortality among melioidosis patients. The factors were diabetes mellitus, type of melioidosis, platelet count, white blood cell count, and urea value. The results showed that bacteremic melioidosis increased the risk of dying by 3.47 (HR: 3.47, 95% confidence intervals [CI]: 1.67-7.23, P = .001) compared to non-bacteremic melioidosis. Based on the blood investigations, the adjusted HRs from the final model showed that all 3 blood investigations were included as the prognostic factors for the disease (low platelet: HR = 1.76, 95% CI: 1.22-2.54, P = .003; high white blood cell: HR = 1.49, 95% CI 1.06-2.11, P = .023; high urea: HR = 2.92, 95% CI: 1.76-4.85, P