Acquisition, co-option, and duplication of the rtx toxin system and the emergence of virulence in Kingella.

Acquisition, co-option, and duplication of the rtx toxin system and the emergence of virulence in Kingella.
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DOI:
10.1038/s41467-023-39939-8
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发表时间:
2023-07-17
影响因子:
16.6
通讯作者:
Planet PJ
Planet PJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Morreale DP;Porsch EA;Kern BK;St Geme JW 3rd;Planet PJ

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金氏菌属包括两种致病菌,即Kingella kingae和Kingella negevensis,以及严格的寄生菌。两个K。kingae和K. Negevensis分泌一种名为RtxA的毒素,这种毒素在Escherosal物种中不存在。在这里,我们提出了一个新的基因组研究属金氏菌,包括新的基因组序列的88个临床分离株,基因分型的另外131个全球分离株,并分析了52个可用的基因组。系统发育证据支持毒素编码操纵子rtxCA是由致病金藻属物种的共同祖先获得的,并且预先存在的I型分泌系统被增选用于毒素输出。随后的基因组重组将毒素机制分布在两个位点上,其中30-35%的K。含有两个rtxA毒素基因拷贝的Kingae菌株。rtxA复制主要是克隆性的,并且与侵袭性疾病相关。用同基因菌株进行的测定表明,rtxA的单拷贝与体外细胞毒性降低相关。因此,我们的研究确定了从寄生虫到病原体进化过渡的关键步骤,包括水平基因转移,现有分泌系统的共同选择和基因复制。金氏菌属包括分泌称为RtxA的毒素的致病性物种,该毒素在真菌物种中不存在。在这里,Morreale等人确定了从细菌到病原体进化过渡的关键步骤,包括毒素编码基因的水平基因转移,现有分泌系统的共同选择和基因复制。
The bacterial genus Kingella includes two pathogenic species, namely Kingella kingae and Kingella negevensis, as well as strictly commensal species. Both K. kingae and K. negevensis secrete a toxin called RtxA that is absent in the commensal species. Here we present a phylogenomic study of the genus Kingella, including new genomic sequences for 88 clinical isolates, genotyping of another 131 global isolates, and analysis of 52 available genomes. The phylogenetic evidence supports that the toxin-encoding operon rtxCA was acquired by a common ancestor of the pathogenic Kingella species, and that a preexisting type-I secretion system was co-opted for toxin export. Subsequent genomic reorganization distributed the toxin machinery across two loci, with 30-35% of K. kingae strains containing two copies of the rtxA toxin gene. The rtxA duplication is largely clonal and is associated with invasive disease. Assays with isogenic strains show that a single copy of rtxA is associated with reduced cytotoxicity in vitro. Thus, our study identifies key steps in the evolutionary transition from commensal to pathogen, including horizontal gene transfer, co-option of an existing secretion system, and gene duplication. The bacterial genus Kingella includes pathogenic species that secrete a toxin called RtxA, which is absent in commensal species. Here, Morreale et al. identify key steps in the evolutionary transition from commensal to pathogen, including horizontal gene transfer of the toxin-encoding genes, co-option of an existing secretion system, and gene duplication.
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