Laboratório de Química e Função de Proteínas e Peptídeos, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, Brazil.
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
FEBS J. 2019 Oct;286(19):3797-3810. doi: 10.1111/febs.15005. Epub 2019 Jul 30.
Klebsiella aerogenes is an important pathogen in healthcare-associated infections. Nevertheless, in comparison to other clinically important pathogens, K. aerogenes population structure, genetic diversity, and pathogenicity remain poorly understood. Here, we elucidate K. aerogenes clonal complexes (CCs) and genomic features associated with resistance and virulence. We present a detailed description of the population structure of K. aerogenes based on 97 publicly available genomes by using both multilocus sequence typing and single-nucleotide polymorphisms extracted from the core genome. We also assessed virulence and resistance profiles using Virulence Finder Database and Comprehensive Antibiotic Resistance Database, respectively. We show that K. aerogenes has an open pangenome and a large effective population size, which account for its high genomic diversity and support that negative selection prevents fixation of most deleterious alleles. The population is structured in at least 10 CCs, including two novel ones identified here, CC9 and CC10. The repertoires of resistance genes comprise a high number of antibiotic efflux proteins as well as narrow- and extended-spectrum β-lactamases. Regarding the population structure, we identified two clusters based on virulence profiles because of the presence of the toxin-encoding clb operon and the siderophore production genes, irp and ybt. Notably, CC3 comprises the majority of K. aerogenes isolates associated with hospital outbreaks, emphasizing the importance of constant monitoring of this pathogen. Collectively, our results may provide a foundation for the development of new therapeutic and surveillance strategies worldwide.
产酸克雷伯菌是医院获得性感染的重要病原体。然而,与其他临床重要的病原体相比,产酸克雷伯菌的种群结构、遗传多样性和致病性仍知之甚少。在这里,我们阐明了与耐药性和毒力相关的产酸克雷伯菌克隆复合体 (CC) 和基因组特征。我们通过使用多位点序列分型和从核心基因组中提取的单核苷酸多态性,对 97 个公开可用的基因组进行了详细的产酸克雷伯菌种群结构描述。我们还分别使用毒力因子数据库和综合抗生素耐药性数据库评估了毒力和耐药性谱。我们表明,产酸克雷伯菌具有开放的泛基因组和较大的有效种群大小,这解释了其高基因组多样性,并支持负选择可防止大多数有害等位基因的固定。该种群至少分为 10 个 CC,包括这里新确定的两个 CC9 和 CC10。耐药基因库包括大量抗生素外排蛋白以及窄谱和广谱β-内酰胺酶。关于种群结构,由于存在编码毒素的 clb 操纵子和铁载体产生基因 irp 和 ybt,我们根据毒力谱确定了两个聚类。值得注意的是,CC3 包含了与医院爆发相关的大多数产酸克雷伯菌分离株,这强调了对这种病原体进行持续监测的重要性。总的来说,我们的研究结果可能为全球范围内新的治疗和监测策略的发展提供基础。