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肯尼亚临床菌株抗生素耐药性和毒力的遗传多样性、分布及基因组特征

Genetic Diversity, Distribution, and Genomic Characterization of Antibiotic Resistance and Virulence of Clinical Strains in Kenya.

作者信息

Kiyaga Shahiid, Kyany'a Cecilia, Muraya Angela W, Smith Hunter J, Mills Emma G, Kibet Caleb, Mboowa Gerald, Musila Lillian

机构信息

Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda.

Department of Emerging Infectious Diseases, United States Army Medical Research Directorate-Africa, Nairobi, Kenya.

出版信息

Front Microbiol. 2022 Mar 14;13:835403. doi: 10.3389/fmicb.2022.835403. eCollection 2022.

Abstract

is a leading cause of nosocomial infections worldwide. It can produce a range of debilitating infections, have a propensity for developing antimicrobial resistance, and present with a variety of potent virulence factors. This study investigated the sequence types (ST), phenotypic antimicrobial susceptibility profiles, and resistance and virulence genes among clinical isolates from urinary tract and skin and soft tissue infections. Fifty-six clinical isolates were obtained from six medical centers across five counties in Kenya between 2015 and 2020. Whole-genome sequencing (WGS) was performed to conduct genomic characterization, sequence typing, and phylogenetic analysis of the isolates. Results showed the presence of globally distributed high-risk clones (ST244 and ST357), local high-risk clones (ST2025, ST455, and ST233), and a novel multidrug-resistant (MDR) clone carrying virulence genes (ST3674). Furthermore, 31% of the study isolates were found to be MDR with phenotypic resistance to a variety of antibiotics, including piperacillin (79%), ticarcillin-clavulanic acid (57%), meropenem (34%), levofloxacin (70%), and cefepime (32%). Several resistance genes were identified, including carbapenemases (ST1203) and (ST357), fluoroquinolone genes, , and , while 14 and 22 different chromosomal mutations were detected in the and genes, respectively. All isolates contained at least three virulence genes. Among the virulence genes identified, was the most abundant (50/56, 89%). About 21% (12/56) of the isolates had the - genotype, while 73% (41/56) of the isolates had the - genotype. This study also discovered 12 novel lineages of , of which one (ST3674) demonstrated both extensive antimicrobial resistance and the highest number of virulence genes (236/242, 98%). Although most high-risk clones were detected in Nairobi County, high-risk and clones of interest were found throughout the country, indicating the local spread of global epidemic clones and the emergence of new strains. Thus, this study illustrates the urgent need for coordinated local, regional, and international antimicrobial resistance surveillance efforts.

摘要

是全球医院感染的主要原因。它可引发一系列使人衰弱的感染,易于产生抗菌药物耐药性,并具有多种强效毒力因子。本研究调查了来自泌尿道、皮肤和软组织感染的临床分离株的序列类型(ST)、表型抗菌药物敏感性谱以及耐药和毒力基因。2015年至2020年期间,从肯尼亚五个县的六个医疗中心获得了56株临床分离株。进行了全基因组测序(WGS)以对分离株进行基因组特征分析、序列分型和系统发育分析。结果显示存在全球分布的高风险克隆(ST244和ST357)、本地高风险克隆(ST2025、ST455和ST233)以及携带毒力基因的新型多重耐药(MDR)克隆(ST3674)。此外,研究发现31%的分离株为多重耐药,对多种抗生素具有表型耐药性,包括哌拉西林(79%)、替卡西林-克拉维酸(57%)、美罗培南(34%)、左氧氟沙星(70%)和头孢吡肟(32%)。鉴定出了几种耐药基因,包括碳青霉烯酶(ST1203)和(ST357)、氟喹诺酮基因、和,同时在和基因中分别检测到14种和22种不同的染色体突变。所有分离株至少含有三个毒力基因。在鉴定出的毒力基因中,最为丰富(50/56,89%)。约21%(12/56)的分离株具有-基因型,而73%(41/56)的分离株具有-基因型。本研究还发现了肺炎克雷伯菌的12个新谱系,其中一个(ST3674)表现出广泛的抗菌药物耐药性且毒力基因数量最多(236/242,98%)。尽管在内罗毕县检测到了大多数高风险克隆,但在全国范围内都发现了高风险和感兴趣的克隆,这表明全球流行克隆在本地传播以及新菌株的出现。因此,本研究表明迫切需要协调地方、区域和国际层面的抗菌药物耐药性监测工作。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c84a/8964364/d14e115f1e89/fmicb-13-835403-g001.jpg

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