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Clinical Burkholderia pseudomallei isolates from north Queensland carry diverse bimABm genes that are associated with central nervous system disease and are phylogenomically distinct from other Australian strains

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PLOS NEGLECTED TROPICAL DISEASES
卷 16, 期 6, 页码 -

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PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pntd.0009482

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The prevalence of the bimA(Bm) variant and antimicrobial resistance mutations were assessed in Burkholderia pseudomallei isolates from Queensland. The bimA(Bm) variant was associated with central nervous system (CNS) disease and novel sequence types were identified. The findings suggest that the bimA(Bm) variant may be a potential therapeutic target for CNS complications.
Background Burkholderia pseudomallei is an environmental gram-negative bacterium that causes the disease melioidosis and is endemic in many countries of the Asia-Pacific region. In Australia, the mortality rate remains high at approximately 10%, despite curative antibiotic treatment being available. The bacterium is almost exclusively found in the endemic region, which spans the tropical Northern Territory and North Queensland, with clusters occasionally present in more temperate climates. Despite being endemic to North Queensland, these infections remain understudied compared to those of the Northern Territory. Methodology/Principal findings This study aimed to assess the prevalence of central nervous system (CNS) disease associated variant bimA(Bm), identify circulating antimicrobial resistance mutations and genetically distinct strains from Queensland, via comparative genomics. From 76 clinical isolates, we identified the bimA(Bm) variant in 20 (26.3%) isolates and in 9 (45%) of the isolates with documented CNS infection (n = 18). Explorative analysis suggests a significant association between isolates carrying the bimA(Bm) variant and CNS disease (OR 2.8, 95% CI 1.3-6.0, P = 0.009) compared with isolates carrying the wildtype bimA(Bp). Furthermore, 50% of isolates were identified as novel multi-locus sequence types, while the bimA(Bm) variant was more commonly identified in isolates with novel sequence types, compared to those with previously described. Additionally, mutations associated with acquired antimicrobial resistance were only identified in 14.5% of all genomes. Conclusions/Significance The findings of this research have provided clinically relevant genomic data of B. pseudomallei in Queensland and suggest that the bimA(Bm) variant may enable risk stratification for the development CNS complications and be a potential therapeutic target.

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