Rodentibacter (R.) heylii is frequently detected in laboratory rodents. Repeats in toxin (RTX) toxins are considered important virulence factors of this major murine pathogen. We evaluated the virulence of a R. heylii strain negative for all known RTX toxin genes and Muribacter (M.) muris, a commensal in mice, in experimental infections of C57BL/6 and BALB/c mice. Experimental intranasal infection with 10⁸ CFU of the pnxI-, pnxII- and pnxIII- R. heylii strain resulted in 75% and 100% mortality in C57BL/6 and BALB/c mice, respectively. In early losses, multiple internal organs were infected and purulent bronchopneumonia was the main pathology. Intranasal application of M. muris did not result in mortality or severe weight loss. Immunoproteomics led to the identification of a surface-associated and specific immunogen, which was designated as R. heylii immunogen A (RhiA) and which was exclusively recognised by sera obtained from mice infected with this R. heylii pathotype. RhiA is a 262.6 kDa large protein containing long imperfect tandem repeats and C-terminal RTX consensus sequences. Immunohistochemical analysis confirmed that this R. heylii pathotype expresses RhiA in the lower respiratory tract. In summary, this study describes a specific immunogen in a virulent R. heylii, strain which is an excellent antigen for pathotype-specific serological screenings and which might carry out RTX-related functions.

海氏啮齿菌 (R.) heylii经常在实验室啮齿动物中检测到。毒素重复序列 (RTX) 毒素被认为是这种主要鼠类病原体的重要毒力因子。我们在 C57BL/6 和 BALB/c 小鼠的实验感染中评估了所有已知 RTX 毒素基因均呈阴性的R. heylii菌株和小鼠共生菌 Muribacter (M.) muris的毒力。用 10 ⁸ CFU 的pnxI -、 pnxII - 和pnxIII - R. heylii菌株进行实验性鼻内感染，导致 C57BL/6 和 BALB/c 小鼠的死亡率分别为 75% 和 100%。早期损失时，多个内脏器官受到感染，化脓性支气管肺炎是主要病理。鼻内施用鼠小孢子不会导致死亡或严重体重减轻。免疫蛋白质组学导致了表面相关的特异性免疫原的鉴定，该免疫原被命名为R. heylii免疫原 A (RhiA)，并且只能被从感染该R. heylii致病型的小鼠获得的血清识别。 RhiA 是一种 262.6 kDa 的大蛋白，含有长的不完美串联重复序列和 C 端 RTX 共有序列。免疫组织化学分析证实，这种R. heylii致病型在下呼吸道表达 RhiA。总之，本研究描述了强毒力R. heylii 菌株中的一种特异性免疫原，它是用于病型特异性血清学筛查的极好抗原，并且可能执行 RTX 相关功能。