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从印度临床分离株中鉴定一株新型类鼻疽伯克霍尔德菌的毒力组学和系统发育组学特征。

Virulome and phylogenomic profiling of a novel Burkholderia pseudomallei strain from an Indian clinical isolate.

机构信息

Centre for Molecular Neurosciences, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.

Center for Emerging and Tropical Diseases, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.

出版信息

Mol Genet Genomics. 2024 Oct 23;299(1):98. doi: 10.1007/s00438-024-02188-5.

Abstract

Highly pathogenic Burkholderia pseudomallei is the causative agent of melioidosis, a neglected tropical disease endemic in Southeast Asian tropical region. This bacterium encompasses diverse virulence factors which further undergo dynamic gene-expression flux as it transits through distinct environmental niches within the host which may lead to manifestation of differential clinical symptoms. B. pseudomallei, is classified as a Tier 1 select agent in the United States and regarded as a risk group 3 organism in India with the potential to be used as bioweapon. Considering these facts, it is vital to uncover both physiological and genetic heterogeneity of B. pseudomallei, particularly to identify any novel virulence factors that may contribute to pathogenicity. B. pseudomallei strain CM000113 was isolated from a clinical case in India, characterized it for its physiological, biochemical, and prominently genetic traits through WGS. It has a type 2 morphotype with faster doubling time and high biofilm producing capacity as compared to Pseudomonas aeruginosa. The genome size is 7.3 Mbp and it is phylogenetically close to B. pseudomallei strain Mahidol 1106a and Burkholderia mallei Turkey 2. We observed genetic heterogeneity, as key virulence factors that were identified shows sequence dissimilarity with reference strains. Additionally, presence of genomic islands, harbouring two virulence factors, GmhA and GmhB2, associated with pathogenesis indicates possibility of horizontal gene transfer. These results emphasize the need for an extensive study focusing the genome of B. pseudomallei and its associated heterogeneity, to identify molecular biomarkers aiding to develop point-of-care diagnostic kits for early diagnosis of melioidosis.

摘要

高致病性伯克霍尔德菌是类鼻疽的病原体,类鼻疽是东南亚热带地区流行的一种被忽视的热带病。这种细菌包含多种毒力因子,当它在宿主的不同环境小生境中穿梭时,这些毒力因子会进一步经历动态的基因表达通量,这可能导致不同的临床症状表现。在 美国,伯克霍尔德菌被归类为 1 级选择剂,在印度被认为是风险组 3 级生物,有可能被用作生物武器。考虑到这些事实,揭示伯克霍尔德菌的生理和遗传异质性是至关重要的,特别是要确定任何可能导致致病性的新毒力因子。伯克霍尔德菌菌株 CM000113 是从印度的一个临床病例中分离出来的,通过 WGS 对其生理、生化和突出的遗传特征进行了表征。与铜绿假单胞菌相比,它具有 2 型形态,倍增时间更快,生物膜生成能力更高。基因组大小为 7.3 Mbp,与伯克霍尔德菌菌株 Mahidol 1106a 和 Burkholderia mallei Turkey 2 亲缘关系密切。我们观察到遗传异质性,因为确定的关键毒力因子与参考菌株的序列存在差异。此外,存在基因组岛,携带与发病机制相关的两个毒力因子 GmhA 和 GmhB2,表明可能发生了水平基因转移。这些结果强调需要对伯克霍尔德菌的基因组及其相关异质性进行广泛研究,以确定有助于开发用于早期诊断类鼻疽的即时诊断试剂盒的分子生物标志物。

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