Uncharacterized and lineage-specific accessory genes within the Proteus mirabilis pan-genome landscape.
Uncharacterized and lineage-specific accessory genes within the Proteus mirabilis pan-genome landscape.
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DOI：
10.1128/msystems.00159-23
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发表时间：
2023-08-31
期刊：
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
--
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奇异变形杆菌(Proteus Mirabilis)是一种革兰氏阴性细菌，以其独特的群体运动性和尿素酶活性而闻名。之前一份关于四个菌株的蛋白质组学报告假设，与其他革兰氏阴性细菌不同，奇异P.mirabilis的基因含量可能不会显示出显著的种内差异。然而，目前还没有对来自不同来源的大量奇异P.mirabilis基因组的全面分析来支持或驳斥这一假说。我们对2060个变形杆菌基因组进行了比较基因组分析。我们对从美国三个大型学术医学中心的临床标本中回收的893个分离株的基因组进行了测序，并结合了来自NCBI组装的1006个基因组和来自公共领域的Illumina Reads组装的161个基因组。我们使用平均核苷酸同一性(ANI)来描述物种和亚种，核心基因组系统发育分析来识别高度相关的奇异P.mirabilis基因组簇，以及泛基因组注释来识别模式菌株HI4320中不存在的感兴趣的基因。在我们的队列中，变形杆菌由10个命名种和5个未鉴定的基因组种组成。奇异巴氏杆菌可分为3个亚种，亚种1占基因组总数的96.7%(1,822/1,883)。奇异P.mirabilis全基因组包括HI4320外15,399个基因，其中34.3%(5,282/15,399)没有推测的功能。亚种1由几个高度相关的克隆群组成。编码可能面向细胞外的蛋白的原噬菌体和基因簇与克隆组相关。在泛基因组中可以鉴定出在模式菌株P.mirabilis HI4320中不存在但与已知毒力相关操纵子同源的未知基因。革兰氏阴性菌利用多种胞外面对因子与真核宿主相互作用。由于种内遗传变异，这些因子可能不存在于特定生物体的模式菌株中，潜在地提供了对宿主-微生物相互作用的不完全理解。与以往关于奇异P.mirabilis的报道不同，但与其他革兰氏阴性细菌相似，P.mirabilis具有镶嵌基因组，其系统发育位置和辅助基因组内容之间存在连锁。奇异P.mirabilis编码多种基因，这些基因可能会影响宿主-微生物动态，而不是模式菌株HI4320中所代表的基因。本工作建立的多样化的全基因组特征菌株库可与反向遗传和感染模型结合使用，以更好地了解辅助基因组内容对细菌生理和感染发病机制的影响。
Proteus mirabilis is a Gram-negative bacterium recognized for its unique swarming motility and urease activity. A previous proteomic report on four strains hypothesized that, unlike other Gram-negative bacteria, P. mirabilis may not exhibit significant intraspecies variation in gene content. However, there has not been a comprehensive analysis of large numbers of P. mirabilis genomes from various sources to support or refute this hypothesis. We performed comparative genomic analysis on 2,060 Proteus genomes. We sequenced the genomes of 893 isolates recovered from clinical specimens from three large US academic medical centers, combined with 1,006 genomes from NCBI Assembly and 161 genomes assembled from Illumina reads in the public domain. We used average nucleotide identity (ANI) to delineate species and subspecies, core genome phylogenetic analysis to identify clusters of highly related P. mirabilis genomes, and pan-genome annotation to identify genes of interest not present in the model P. mirabilis strain HI4320. Within our cohort, Proteus is composed of 10 named species and 5 uncharacterized genomospecies. P. mirabilis can be subdivided into three subspecies; subspecies 1 represented 96.7% (1,822/1,883) of all genomes. The P. mirabilis pan-genome includes 15,399 genes outside of HI4320, and 34.3% (5,282/15,399) of these genes have no putative assigned function. Subspecies 1 is composed of several highly related clonal groups. Prophages and gene clusters encoding putatively extracellular-facing proteins are associated with clonal groups. Uncharacterized genes not present in the model strain P. mirabilis HI4320 but with homology to known virulence-associated operons can be identified within the pan-genome. Gram-negative bacteria use a variety of extracellular facing factors to interact with eukaryotic hosts. Due to intraspecies genetic variability, these factors may not be present in the model strain for a given organism, potentially providing incomplete understanding of host-microbial interactions. In contrast to previous reports on P. mirabilis, but similar to other Gram-negative bacteria, P. mirabilis has a mosaic genome with a linkage between phylogenetic position and accessory genome content. P. mirabilis encodes a variety of genes that may impact host-microbe dynamics beyond what is represented in the model strain HI4320. The diverse, whole-genome characterized strain bank from this work can be used in conjunction with reverse genetic and infection models to better understand the impact of accessory genome content on bacterial physiology and pathogenesis of infection.
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