Pathogenicity and genomic features of vapN-harboring Rhodococcus equi isolated from human patients
Pathogenicity and genomic features of vapN-harboring Rhodococcus equi isolated from human patients
复制标题
DOI：
10.1016/j.ijmm.2021.151519
复制
发表时间：
2021-07-16
影响因子：
4.1
通讯作者：
Takai, Shinji
中科院分区：
文献类型：
--
作者：
Suzuki, Yasunori;Kubota, Hiroaki;Takai, Shinji
马红球菌是一种腐生土壤细菌和细胞内病原体，可引起马驹难治性化脓性肺炎，并已成为人畜共患疾病的致病原因。几项研究报告了由马罗氏菌引起的人类感染，该马罗氏菌携带最近描述的第三种毒力质粒，即反刍动物相关的 pVAPN，它携带 vapN 毒力决定子。在此，我们分析了从患有和未患有艾滋病毒/艾滋病的人类患者中分离出的九种携带 vapN 的马病毒的致病性和基因组特征。其中四种菌株在培养的巨噬细胞中显示出显着的 VapN 产生和增殖。这些菌株在小鼠体内接种 1.0 x 10(8) CFU 后具有致命致病性，并在肝脏和脾脏中产生类似于人类观察到的坏死性肉芽肿性炎症。此外，我们还确定了所有九个菌株的整个基因组序列。序列长度为5.0-5.3 Mbp，GC含量为68.7%-68.8%。所有菌株均含有 120-或 125-kbp 线性质粒，该质粒携带 vapN（I 型或 II 型 pVAPN），根据 3' 侧远端序列的差异进行分类。有趣的是，具有几乎相同类型的 pVAPN 的菌株之间的 VapN 产量存在显着差异，变化仅限于几个 SNP 和短碱基对插入缺失。 VapN产生菌株所拥有的pVAPN序列没有保留任何共同的遗传特征，需要更详细的分析，包括染色体基因，以进一步阐明VapN表达机制。
Rhodococcus equi is a saprophytic soil bacterium and intracellular pathogen that causes refractory suppurative pneumonia in foals and has emerged as a pathogenic cause of zoonotic disease. Several studies have reported human infections caused by R. equi harboring a recently described third type of virulence plasmid, the ruminant-associated pVAPN, which carries the vapN virulence determinant. Herein, we analyzed pathogenicity and genomic features of nine vapN-harboring R. equi isolated from human patients with and without HIV/AIDS. Four of these strains showed significant VapN production and proliferation in cultured macrophages. These strains were lethally pathogenic after inoculation with 1.0 x 10(8) CFU in mice and reproduced a necrotizing granulomatous inflammation in the liver and spleen similar to that observed in humans. Additionally, we determined entire genome sequences of all nine strains. Lengths of sequences were 5.0-5.3 Mbp, and GC contents were 68.7 %-68.8 %. All strains harbored a 120- or 125-kbp linear plasmid carrying vapN (Type I or Type II pVAPN) classified on the basis of differences in the distal sequences on the 3' side. Interestingly, VapN production differed significantly among strains harboring nearly identical types of pVAPN with variation limited to several SNPs and short base pair indels. The pVAPN sequences possessed by the VapN-producing strains did not retain any common genetic characteristics, and more detailed analyses, including chromosomal genes, are needed to further elucidate the VapN expression mechanism.