Genomic and pathogenic characterization of RTX toxin producing Rodentibacter sp. that is closely related to Rodentibacter haemolyticus
Genomic and pathogenic characterization of RTX toxin producing Rodentibacter sp. that is closely related to Rodentibacter haemolyticus
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产生 RTX 毒素的啮齿菌属的基因组和致病性特征。
DOI：
10.1016/j.meegid.2022.105314
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Ike Fumio
中科院分区：
文献类型：
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作者：
Sasaki Hiraku;Ueshiba Hidehiro;Yanagisawa Naoko;Itoh Yuta;Ishikawa Hiroki;Shigenaga Ayako;Benga Laurentiu;Ike Fumio
啮齿类是通常从实验室啮齿动物的上呼吸道分离的机会致病菌。特别是R.嗜肺性的河在啮齿动物群体中，需要相当谨慎，因为它们会导致啮齿动物致命的肺炎。本文报道了一新种，R.溶血性弧菌，最近已被分类在属，和一个非常密切相关的菌株，啮齿动物属。JRC菌株已在日本分离。本研究通过基因组和致病性分析对JRC菌株进行了研究。JRC株的基因组测序草案确定了几个编码推定毒性蛋白的基因，包括溶血素和粘附素。此外，我们还在该菌基因组中发现了一个新的RTX（repeats-in-structural toxin，结构重复序列毒素）毒素基因，该基因被预测产生类似于肠杆菌科的关键毒力因子（critical virtual factor，RTXIA）。RTX毒素（RTXIA）的浓缩培养上清对RAW264.7细胞具有细胞毒性。用抗CD 11 a预孵育减弱了细胞溶解，表明含有RTXIA的浓缩培养物上清液是细胞表面LFA-1介导的细胞溶解素。用5只雌性BALB/c-Rag 2 −/−小鼠鼻内感染JRC菌株的实验显示60%的致死率，与R菌株无显著差异。嗜肺性ATCC 35149 T使用对数秩检验。结合我们的发现，RTXIA具有几乎相同的氨基酸序列（98%的同一性）的ofR。hemolyticus 1625/19 T，这些结果强烈地表明RTXIA产生菌JRC（和相关R.溶血性弧菌）对免疫缺陷啮齿类动物是致病性的，在实验室啮齿类动物群落中应排除这两种病原体。
Rodentibacterspp. are opportunistic pathogens that are often isolated from the upper respiratory tracts of laboratory rodents. In particular,R. pneumotropicusandR. heyliirequire considerable caution in rodent colonies, as they cause lethal pneumonia in rodents. A new species,R. haemolyticus, has recently been classified in the genus, and a very closely related strain,Rodentibactersp. strain JRC, has been isolated in Japan. This study focused on strain JRC by performing genomic and pathogenic analyses. Draft genome sequencing of strain JRC identified several genes coding for putative virulent proteins, including hemolysin and adhesin. Furthermore, we found a new RTX (repeats-in-structural toxin) toxin gene in the genome, which was predicted to produce a critical virulence factor (RTXIA) similar toEnterobacteriaceae. The concentrated culture supernatant containing RTX toxin (RTXIA) showed cytotoxicity toward RAW264.7 cells. Pre-incubation with anti-CD11a attenuated the cytolysis, suggesting that the concentrated culture supernatant containing RTXIA is cell surface LFA-1 mediated cytolysin. Experimental infection of strain JRC intranasally with 5 female BALB/c-Rag2−/−mice showed 60% lethality and was not significantly different from those ofR. pneumotropicusATCC 35149Tusing the log-rank test. Combined with our finding that RTXIA has an almost identical amino acid sequence (98% identity) to that ofR. haemolyticus1625/19T, these results strongly suggest that RTXIA-producing strain JRC (and relatedR. haemolyticus) is pathogenic to immunodeficient rodents, and both agents should be excluded in laboratory rodent colonies.