Melioidosis in Africa: Should we be Looking more Closely?

Birnie, Emma; Wiersinga, W. Joost; Limmathurotsakul, Direk; Grobusch, Martin P.

doi:10.2217/fmb.14.113

Cited by 27 publications

(23 citation statements)

References 33 publications

(68 reference statements)

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“…Pneumonia is the presenting symptom in most adult patients [3] and results in a rapidly progressive illness with a high mortality up to 40% [1, 3]. The disease is caused by Burkholderia pseudomallei , a facultative intracellular Gram-negative bacterium that is commonly found in the soil from countries located between 20° north latitude and 20° south latitude [1, 2, 4]. Due to its high lethality, poor sensitivity to antibiotics, wide availability and easy dissemination, it has been classified as a Tier 1 biological threat agent.…”

Section: Introductionmentioning

confidence: 99%

The gut microbiota as a modulator of innate immunity during melioidosis

et al. 2017

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BackgroundMelioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is an emerging cause of pneumonia-derived sepsis in the tropics. The gut microbiota supports local mucosal immunity and is increasingly recognized as a protective mediator in host defenses against systemic infection. Here, we aimed to characterize the composition and function of the intestinal microbiota during experimental melioidosis.Methodology/Principal findingsC57BL/6 mice were infected intranasally with B. pseudomallei and sacrificed at different time points to assess bacterial loads and inflammation. In selected experiments, the gut microbiota was disrupted with broad-spectrum antibiotics prior to inoculation. Fecal bacterial composition was analyzed by means of IS-pro, a 16S-23S interspacer region-based profiling method. A marked shift in fecal bacterial composition was seen in all mice during systemic B. pseudomallei infection with a strong increase in Proteobacteria and decrease in Actinobacteria, with an increase in bacterial diversity. We found enhanced early dissemination of B. pseudomallei and systemic inflammation during experimental melioidosis in microbiota-disrupted mice compared with controls. Whole-genome transcriptional profiling of the lung identified several genes that were differentially expressed between mice with a normal or disrupted intestinal microbiota. Genes involved in acute phase signaling, including macrophage-related signaling pathways were significantly elevated in microbiota disrupted mice. Compared with controls, alveolar macrophages derived from antibiotic pretreated mice showed a diminished capacity to phagocytose B. pseudomallei. This might in part explain the observed protective effect of the gut microbiota in the host defense against pneumonia-derived melioidosis.Conclusions/SignificanceTaken together, these data identify the gut microbiota as a potential modulator of innate immunity during B. pseudomallei infection.

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Section: Introductionmentioning

confidence: 99%

The gut microbiota as a modulator of innate immunity during melioidosis

et al. 2017

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“…9 Despite limited clinical reports, isolation of B. pseudomallei from soil and animals in Africa confirms hypotheses that melioidosis is widely distributed across the region. 10 Additionally, a novelty of B. pseudomallei is its ability to survive in extreme conditions, such as distilled water (for >16 years), 11 nutrient-depleted soil, 12 or desert environments. 10,13 Rivers may also be carriers and potential sentinels for B. pseudomallei, showing a shift in presence from 9% during the dry season to 57% in the rainy season (mainly in turbid water).…”

Section: Epidemiology: the Expanding Knowledge On The Distribution Ofmentioning

confidence: 99%

“…10 Additionally, a novelty of B. pseudomallei is its ability to survive in extreme conditions, such as distilled water (for >16 years), 11 nutrient-depleted soil, 12 or desert environments. 10,13 Rivers may also be carriers and potential sentinels for B. pseudomallei, showing a shift in presence from 9% during the dry season to 57% in the rainy season (mainly in turbid water). 14 Owing to a lack of both awareness among physicians and diagnostic microbiological laboratories in low-income rural areas, melioidosis remains grossly underdiagnosed worldwide.…”

Section: Epidemiology: the Expanding Knowledge On The Distribution Ofmentioning

confidence: 99%

Melioidosis: A Neglected Cause of Community-Acquired Pneumonia

Virk

Mukhopadhyay

Wiersinga

2020

Semin Respir Crit Care Med

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AbstractMelioidosis, caused by the facultative intracellular gram-negative pathogen Burkholderia pseudomallei, is an emerging cause of community-acquired pneumonia across the tropics. The majority of patients present with pneumonia with or without sepsis, but localized and asymptomatic infection is also well recognized. Recent modeling and epidemiological studies have demonstrated the widespread presence of B. pseudomallei in otherwise unrecognized regions with a predicted mortality of 90,000 deaths worldwide. Innovative environmental studies are also uncovering how hydrodynamic, pedology, fauna, and weather events influence geographic distribution and incidence of melioidosis cases. Of concern is the changes associated with global warming, which will be conducive to B. pseudomallei in combination with the global diabetes pandemic. In fact, over 80% of patient developing melioidosis have underlying comorbidities. For this great mimicker, culture remains the mainstay of diagnosis and despite availability of other assays, challenges still remain in reducing time to diagnosis and avoiding misdiagnosis. With institution of timely antimicrobials such as ceftazidime and supportive intensive care, overall mortality can be reduced to 10%, although this can still be as high as 50% in poorly resourced areas. Promise is on the horizon with the first human vaccine trials being planned for 2021. Meanwhile new multiomics techniques are giving us a better understanding of the role of virulence and host–pathogen interactions on patient outcomes.

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“…However, few surveys for B . pseudomallei and its near neighbors have been conducted outside of endemic areas [ 26 , 27 ] despite the ongoing discovery of new species in this group [ 28 ]. To address this knowledge gap, we surveyed for B .…”

Section: Introductionmentioning

confidence: 99%

Diverse Burkholderia Species Isolated from Soils in the Southern United States with No Evidence of B. pseudomallei

et al. 2015

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The global distribution of the soil-dwelling bacterium Burkholderia pseudomallei, causative agent of melioidosis, is poorly understood. We used established culturing methods developed for B. pseudomallei to isolate Burkholderia species from soil collected at 18 sampling sites in three states in the southern United States (Arizona (n = 4), Florida (n = 7), and Louisiana (n = 7)). Using multi-locus sequence typing (MLST) of seven genes, we identified 35 Burkholderia isolates from these soil samples. All species belonged to the B. cepacia complex (Bcc), including B. cenocepacia, B. cepacia, B. contaminans, B. diffusa, B. metallica, B. seminalis, B. vietnamiensis and two unnamed members of the Bcc. The MLST analysis provided a high level of resolution among and within these species. Despite previous clinical cases within the U.S. involving B. pseudomallei and its close phylogenetic relatives, we did not isolate any of these taxa. The Bcc contains a number of opportunistic pathogens that cause infections in cystic fibrosis patients. Interestingly, we found that B. vietnamiensis was present in soil from all three states, suggesting it may be a common component in southern U.S. soils. Most of the Burkholderia isolates collected in this study were from Florida (30/35; 86%), which may be due to the combination of relatively moist, sandy, and acidic soils found there compared to the other two states. We also investigated one MLST gene, recA, for its ability to identify species within Burkholderia. A 365bp fragment of recA recovered nearly the same species-level identification as MLST, thus demonstrating its cost effective utility when conducting environmental surveys for Burkholderia. Although we did not find B. pseudomallei, our findings document that other diverse Burkholderia species are present in soils in the southern United States.

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Melioidosis in Africa: Should we be Looking more Closely?

Cited by 27 publications

References 33 publications

The gut microbiota as a modulator of innate immunity during melioidosis

The gut microbiota as a modulator of innate immunity during melioidosis

Melioidosis: A Neglected Cause of Community-Acquired Pneumonia

Diverse Burkholderia Species Isolated from Soils in the Southern United States with No Evidence of B. pseudomallei

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