The Expanding Global Footprint of Burkholderia pseudomallei and Melioidosis

Currie, Bart J.; Meumann, Ella M.; Kaestli, Mirjam

doi:10.4269/ajtmh.23-0223

Cited by 5 publications

(5 citation statements)

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“…Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei , is a disease endemic in Southeast Asia and northern Australia, with increasing cases across the Pacific, South Asia, Africa and the Americas ( Limmathurotsakul et al., 2016 ; Currie et al, 2023 ; Meumann et al., 2024 ). Infections can be caused through subcutaneous inoculation, inhalation, or ingestion of the bacterium.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of macrophage infectivity potentiator in Burkholderia pseudomallei suppresses pro-inflammatory responses in murine macrophages

Iwasaki,

Bzdyl,

Lin-Sullivan

et al. 2024

Front. Cell. Infect. Microbiol.

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IntroductionMelioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is a disease endemic in many tropical countries globally. Clinical presentation is highly variable, ranging from asymptomatic to fatal septicemia, and thus the outcome of infection can depend on the host immune responses. The aims of this study were to firstly, characterize the macrophage immune response to B. pseudomallei and secondly, to determine whether the immune response was modified in the presence of novel inhibitors targeting the virulence factor, the macrophage infectivity potentiator (Mip) protein. We hypothesized that inhibition of Mip in B. pseudomallei would disarm the bacteria and result in a host beneficial immune response.MethodsMurine macrophage J774A.1 cells were infected with B. pseudomallei K96243 in the presence of small-molecule inhibitors targeting the Mip protein. RNA-sequencing was performed on infected cells four hours post-infection. Secreted cytokines and lactose dehydrogenase were measured in cell culture supernatants 24 hours post-infection. Viable, intracellular B. pseudomallei in macrophages were also enumerated 24 hours post-infection.ResultsGlobal transcriptional profiling of macrophages infected with B. pseudomallei by RNA-seq demonstrated upregulation of immune-associated genes, in particular a significant enrichment of genes in the TNF signaling pathway. Treatment of B. pseudomallei-infected macrophages with the Mip inhibitor, AN_CH_37 resulted in a 5.3-fold reduction of il1b when compared to cells treated with DMSO, which the inhibitors were solubilized in. A statistically significant reduction in IL-1β levels in culture supernatants was seen 24 hours post-infection with AN_CH_37, as well as other pro-inflammatory cytokines, namely IL-6 and TNF-α. Treatment with AN_CH_37 also reduced the survival of B. pseudomallei in macrophages after 24 hours which was accompanied by a significant reduction in B. pseudomallei-induced cytotoxicity as determined by lactate dehydrogenase release.DiscussionThese data highlight the potential to utilize Mip inhibitors in reducing potentially harmful pro-inflammatory responses resulting from B. pseudomallei infection in macrophages. This could be of significance since overstimulation of pro-inflammatory responses can result in immunopathology, tissue damage and septic shock.

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Section: Introductionmentioning

confidence: 99%

Inhibition of macrophage infectivity potentiator in Burkholderia pseudomallei suppresses pro-inflammatory responses in murine macrophages

Iwasaki,

Bzdyl,

Lin-Sullivan

et al. 2024

Front. Cell. Infect. Microbiol.

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“…Melioidosis, a systemic infectious disease prevalent in Southeast Asia, Australia, and Southern China, is caused by B. pseudomallei [1,2]. This disease manifests with symptoms like pulmonary inflammation and persistent cutaneous lesions.…”

Section: Introductionmentioning

confidence: 99%

Anti-Hcp1 Monoclonal Antibody Is Protective against Burkholderia pseudomallei Infection via Recognizing Amino Acids at Asp95-Leu114

Wu,

Rao,

Liu

et al. 2023

Pathogens

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Melioidosis, a severe tropical illness caused by Burkholderia pseudomallei, poses significant treatment challenges due to limited therapeutic options and the absence of effective vaccines. The pathogen’s intrinsic resistance to numerous antibiotics and propensity to induce sepsis during acute infections further complicate management strategies. Thus, exploring alternative methods for prevention and treatment is crucial. Monoclonal antibodies (mAbs) have emerged as a promising strategy for the prevention and treatment of infectious diseases. This study focused on generating three mAbs (13F1, 14G11, and 15D9) targeting hemolysin-coregulated protein 1 (Hcp1), a protein involved in the type VI secretion system cluster 1 (T6SS1) of B. pseudomallei. Notably, pretreatment with 13F1 mAb significantly reduced the intracellular survival of B. pseudomallei and inhibited the formation of macrophage-derived multinucleated giant cells (MNGCs). This protective effect was also observed in vivo. We identified a sequence of amino acids (Asp95-Leu114) within Hcp1 as the likely binding site for 13F1 mAb. In summary, our findings reveal that 13F1 mAb counteracts infection by targeting Hcp1, offering potential new targets and insights for melioidosis prevention.

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“…Melioidosis is also being detected in the United States. Most of the cases have been related to travel to areas with endemic melioidosis or to exposure to contaminated imported products (Dawson et al, 2021;Gee et al, 2022;Currie et al, 2023). However, three non-travel-associated cases of melioidosis in Mississippi, which were found to be genetically associated with B. pseudomallei isolated locally from soil and water samples, clearly suggest that B. pseudomallei is endemic in the southern region of the USA (CDC, 2022;Currie, et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

“…Most of the cases have been related to travel to areas with endemic melioidosis or to exposure to contaminated imported products (Dawson et al, 2021;Gee et al, 2022;Currie et al, 2023). However, three non-travel-associated cases of melioidosis in Mississippi, which were found to be genetically associated with B. pseudomallei isolated locally from soil and water samples, clearly suggest that B. pseudomallei is endemic in the southern region of the USA (CDC, 2022;Currie, et al, 2023). Similar cases in Texas have been reported that were suggestive of local acquisition; but attempts to isolate a comparable strain from environmental samples were unsuccessful (Cossaboom et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Detection of low-level animal-to-animal transmission in BALB/c mouse models of melioidosis

Klimko,

Barnes,

Rill

et al. 2023

Front. Bacteriol.

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Burkholderia pseudomallei, the causative agent of melioidosis, has two phases of infection. The acute phase occurs shortly after infection and is associated with bacterial sepsis, potentially leading to death, whilst the chronic phase occurs when infection persists for longer periods or is asymptomatic for months or years. BALB/c mice are more susceptible to melioidosis compared to C57BL/6 mice and are routinely models for the acute phase of infection. However, in some instances when medical countermeasures are being evaluated, mice continue to succumb to disease throughout the course of the experimental infection. Whilst B. pseudomallei is not known to be transmitted from mouse-to-mouse, we hypothesized that mice that have recovered from infection after medical countermeasure intervention may become reinfected from chronically infected mice. We tested this hypothesis by cohousing naïve mice with mice exposed to B. pseudomallei by the inhalational or intraperitoneal routes in either static or ventilated caging. Mice that were exposed to aerosolized B. pseudomallei transmitted the bacterium to approximately 4% of their naïve cagemates, whereas mice that were infected by the intraperitoneal route transmitted to approximately 8% of their naïve cagemates. Whilst the exact route of transmission remains to be determined, the results of this study showed that low levels of mouse-to-mouse transmission of B. pseudomallei are possible. We conclude that although the chance of reinfection is low amongst mice housed in the same cage, this possible scenario should be considered when interpreting data from the BALB/c mouse model of melioidosis in lengthy studies.

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The Expanding Global Footprint of Burkholderia pseudomallei and Melioidosis

Cited by 5 publications

References 36 publications

Inhibition of macrophage infectivity potentiator in Burkholderia pseudomallei suppresses pro-inflammatory responses in murine macrophages

Inhibition of macrophage infectivity potentiator in Burkholderia pseudomallei suppresses pro-inflammatory responses in murine macrophages

Anti-Hcp1 Monoclonal Antibody Is Protective against Burkholderia pseudomallei Infection via Recognizing Amino Acids at Asp95-Leu114

Detection of low-level animal-to-animal transmission in BALB/c mouse models of melioidosis

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