A Rodentibacter heylii strain lacking all known RTX toxin genes is highly virulent in C57BL/6 and BALB/c mice in contrast to Muribacter muris

Abstract Background Rodentibacter (R.) heylii and Muribacter (M.) muris are frequently detected in laboratory rodents. Repeats in toxin (RTX) toxins are considered to be important virulent factors in R. pneumotropicus and R. heylii. As many R. heylii isolates do not carry genes encoding known RTX toxins we hypothesized that these isolates are at the most moderately virulent or even avirulent as M. muris . To test this hypothesis, we evaluated the virulence of R. heylii and M. muris strains negative for all known RTX toxin genes in experimental infections of C57BL/6 and BALB/c mice. Results Experimental intranasal infection with 10 8 colony forming units (CFU) of a pnx I-, pnx II- and pnx III-negative R. heylii strain resulted in 75% and 100% mortality of C57BL/6 and BALB/c mice, respectively. Infections of multiple internal organs such as lung and genito-urinary tract were recorded. Purulent bronchopneumonia was a common finding in lungs of early losses. Application of 10 4 CFU of the same R. heylii strain was neither associated with clinical signs nor dissemination, but with efficient colonization of the upper respiratory tract. Intranasal application of M. muris in different doses ranging from 10 4 to 10 8 CFU did not result in mortality or severe weight loss but efficient colonization and induction of systemic M. muris specific IgG in most animals. Conclusion The current study reveals high virulence of R. heylii strain SF27GVG carrying none of the known RTX toxin genes in wildtype mice. This result questions the validity of estimating virulence in the genus Rodentibacter by profiling of pnx toxin genes. Suitable colonization models for future investigations were established for R. heylii and M. muris . Application of M. muris was associated with a systemic IgG immune response and cultural detection in draining lymph nodes in most animals indicating infection and not sole colonization.