Laboratory of Animal Hygiene, Kitasato University School of Veterinary Medicine, Aomori, Japan.
Department of Microbiology, Tokyo Metropolitan Institute of Public Health, Tokyo, Japan.
Int J Med Microbiol. 2021 Aug;311(6):151519. doi: 10.1016/j.ijmm.2021.151519. Epub 2021 Jul 2.
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 × 10 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.
马红球菌是一种腐生土壤细菌和细胞内病原体，可导致幼驹难治性化脓性肺炎，并已成为人畜共患病的致病原因。有几项研究报道了人类感染了最近描述的第三种毒力质粒——反刍动物相关 pVAPN 的马红球菌，该质粒携带 vapN 毒力决定簇。在此，我们分析了来自人类 HIV/AIDS 患者和非 HIV/AIDS 患者的 9 株 vapN 携带马红球菌的致病性和基因组特征。其中 4 株在培养的巨噬细胞中显示出显著的 vapN 产生和增殖。这些菌株在接种 1.0×10 CFU 后对小鼠具有致死性致病性，并在肝脏和脾脏中复制出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 9 株菌的全基因组序列。序列长度为 5.0-5.3 Mbp，GC 含量为 68.7%-68.8%。所有菌株均携带一个 120-或 125-kbp 线性质粒，携带 vapN（I 型或 II 型 pVAPN），根据 3'侧末端序列的差异进行分类。有趣的是，携带几乎相同类型 pVAPN 的菌株之间 vapN 的产生差异显著，变异仅限于几个 SNP 和短碱基对插入缺失。产生 vapN 的菌株所携带的 pVAPN 序列不具有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。
