印度耐碳青霉烯类鲍曼不动杆菌遗传景观的比较分析:全基因组计算研究

Rhythm Sharma, Dinesh Lakhanpal
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摘要

鲍曼不动杆菌(Acinetobacter baumannii)是一种革兰氏阴性需氧细菌,是造成耐多药院内感染的罪魁祸首,尤其是在重症监护病房。本研究调查了在印度人群中流行的鲍曼不动杆菌临床相关菌株的遗传多样性、抗菌基因、毒力因子、移动遗传因子和耐药基因,这与其他亚洲国家(包括中国、东南亚和泰国)的报告一致。利用公开的基因组数据对耐碳青霉烯类鲍曼不动杆菌菌株进行了全面分析。泛基因组扇形分析表明,该病原体的基因组结构是开放的,这表明该病原体具有持续基因进化的潜力。研究发现了重要的耐药基因,包括 blaOXA-23、AdeIJK 和 AdeFGH 型外排泵以及碳青霉烯酶。OmpA、磷脂酶和 Csu pili 等致病因子普遍存在,增强了该细菌的致病性。此外,还发现了包括 Tn2006 和 ISAba1/blaOXA-23 基因组合在内的移动遗传因子,凸显了耐药基因快速传播背后的机制。我们采用了减法蛋白质组学来鉴定对细菌至关重要但与人类非同源的核心蛋白质,从而突出了它们作为潜在药物靶点的作用。这项分析确定了 2165 个核心蛋白质,其中 550 个非同源的重要蛋白质位于细胞质中。根据这些蛋白质的稳定性和参与重要通路的情况对其进行了进一步评估,我们确定了 15 个可作为抗菌药物潜在靶点的可药物蛋白。这些发现强调了持续监控、创新药物开发和靶向治疗策略的迫切需要,以减轻耐多药鲍曼不动杆菌对医疗机构的影响。解决鲍曼不动杆菌的抗菌药耐药性问题仍然是全球健康的当务之急,尤其是在印度这样的高负担地区,耐药菌株的流行率非常高。这项研究为今后对抗这种可怕病原体的研究和开发奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comparative analysis of genetic landscape of carbapenem-resistant Acinetobacter baumannii in India: A computational whole-genome study
Acinetobacter baumannii is a Gram-negative, aerobic bacterium responsible for multidrug-resistant nosocomial infections, especially in Intensive Care Units. This study investigated the genetic diversity, antimicrobial genes, virulence factors, and mobile genetic elements, resistance genes in clinically relevant strains of A. baumannii circulating in the Indian population, consistent with reports from other Asian countries, including China, Southeast Asia, and Thailand. A comprehensive analysis of carbapenem-resistant A. baumannii strains was conducted using publicly available genomic data. Pan-genome fanalysis revealed an open genome structure, indicating the pathogen's potential for ongoing genetic evolution. The study identified significant resistance genes, including blaOXA-23, AdeIJK and AdeFGH type efflux pumps, and carbapenemases. Virulence factors such as OmpA, phospholipase, and Csu pili were prevalent, contributing to the bacterium's pathogenicity. Mobile genetic elements, including Tn2006 and ISAba1/blaOXA-23 gene combinations, were also identified, highlighting the mechanisms behind the rapid spread of resistance genes. Subtractive proteomics was employed to identify core proteins essential to the bacterium but non-homologous to humans, highlighting them as potential drug targets. This analysis identified 2165 core proteins, with 550 non-homologous essential proteins located in the cytoplasm. Further evaluation of these proteins based on stability and involvement in essential pathways, we identified 15 druggable proteins as potential targets for antimicrobial agents. The findings underscore the critical need for continuous surveillance, innovative drug development, and targeted therapeutic strategies to mitigate the impact of multidrug-resistant A. baumannii in healthcare settings. Addressing antimicrobial resistance in A. baumannii remains a global health priority, especially in high-burden regions like India, where the prevalence of resistant strains is notably high. This study provides a foundation for future research and development in combating this formidable pathogen.
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