Comparative Genomic Analysis of Citrobacter and Key Genes Essential for the Pathogenicity of Citrobacter koseri
Comparative Genomic Analysis of Citrobacter and Key Genes Essential for the Pathogenicity of Citrobacter koseri
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柠檬酸杆菌及科塞柠檬酸杆菌致病性关键基因的比较基因组分析
DOI：
10.3389/fmicb.2019.02774
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发表时间：
2019-12-06
影响因子：
5.2
通讯作者：
Liu, Bin
中科院分区：
文献类型：
--
作者：
Yuan, Chao;Yin, Zhiqiu;Liu, Bin
柠檬酸杆菌属是与医院和社区获得性感染有关的机会性细菌病原体。在柠檬酸杆菌属中，科氏柠檬酸杆菌经常从临床材料中分离，并且已知其在新生儿和免疫功能低下的个体中引起脑膜炎和脑脓肿。然而，柠檬酸杆菌的毒力决定因素在很大程度上仍然未知。基于传统方法，柠檬酸杆菌属已被划分为11个种，但这一直是有问题的。在这里，我们根据来自129个柠檬酸杆菌基因组的全基因组序列（WGS）数据，确定了一个改进的，详细的，更准确的柠檬酸杆菌属的遗传学，其中31个在这项研究中进行了测序。用核心基因组单核苷酸多态性（SNPs）构建的最大似然（ML）遗传学将所有柠檬酸杆菌属分离株分为11个不同的组，所有C。Koseri菌株聚为一个组。为了进行全面和系统的比较基因组分析，我们调查了柠檬酸杆菌属中毒力因子、抗性基因和大分子分泌系统的分布。此外，结合组特异性基因分析，我们确定了一个铁转运的关键基因簇，它存在于C。koseri类群中，而在其他类群中缺失，表明高致病性岛（HPI）簇可能是影响克氏锥虫致病性的重要因素。koseri。动物实验表明，HPI簇的丢失显著降低了C。Koseri毒力。此外，我们还提供了证据来解释为什么弗氏柠檬酸杆菌比C. koseri对几种抗生素的模拟试验总的来说，我们的数据揭示了新的毒力集群的主要致病性C。koseri菌株，这是阐明这些重要病原体的毒力机制的基础。
Citrobacter species are opportunistic bacterial pathogens that have been implicated in both nosocomial and community-acquired infections. Among the genus Citrobacter, Citrobacter koseri is often isolated from clinical material, and has been known to cause meningitis and brain abscess in neonates and immunocompromised individuals. The virulence determinants of Citrobacter, however, remain largely unknown. Based on traditional methods, the genus Citrobacter has been divided into 11 species, but this has been problematic. Here, we determined an improved, detailed, and more accurate phylogeny of the genus Citrobacter based on whole genome sequence (WGS) data from 129 Citrobacter genomes, 31 of which were sequenced in this study. A maximum likelihood (ML) phylogeny constructed with core genome single-nucleotide polymorphisms (SNPs) classified all Citrobacter isolates into 11 distinct groups, with all C. koseri strains clustering into a single group. For comprehensive and systematic comparative genomic analyses, we investigated the distribution of virulence factors, resistance genes, and macromolecular secretion systems among the Citrobacter genus. Moreover, combined with group-specific genes analysis, we identified a key gene cluster for iron transport, which is present in the C. koseri group, but absent in other the groups, suggesting that the high-pathogenicity island (HPI) cluster may be important for the pathogenicity of C. koseri. Animal experiments showed that loss of the HPI cluster significantly decreased C. koseri virulence in mice and rat. Further, we provide evidence to explain why Citrobacter freundii is less susceptible than C. koseri to several antibiotics in silico. Overall, our data reveal novel virulence clusters specific to the predominantly pathogenic C. koseri strains, which form the basis for elucidating the virulence mechanisms underlying these important pathogens.