Genomic and pathogenic characterization of RTX toxin producing Rodentibacter sp. that is closely related to Rodentibacter haemolyticus

• Published in: Infection, genetics and evolution genetics and evolution, 2022-08, Vol.102, p.105314-105314, Article 105314
• Main Authors: Sasaki, Hiraku, Ueshiba, Hidehiro, Yanagisawa, Naoko, Itoh, Yuta, Ishikawa, Hiroki, Shigenaga, Ayako, Benga, Laurentiu, Ike, Fumio
• Format: Article
• Language: English
• Subjects: Hemolysis; LFA-1; Rodentibacter haemolyticus; Rodentibacter sp; RTX toxin
• ISSN: 1567-1348; 1567-7257
• DOI: 10.1016/j.meegid.2022.105314

Rodentibacter spp. are opportunistic pathogens that are often isolated from the upper respiratory tracts of laboratory rodents. In particular, R. pneumotropicus and R. heylii require 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, Rodentibacter sp. 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 to Enterobacteriaceae. 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 of R. pneumotropicus ATCC 35149T using the log-rank test. Combined with our finding that RTXIA has an almost identical amino acid sequence (98% identity) to that of R. haemolyticus 1625/19T, these results strongly suggest that RTXIA-producing strain JRC (and related R. haemolyticus) is pathogenic to immunodeficient rodents, and both agents should be excluded in laboratory rodent colonies. •Rodentibacter sp. strain JRC and R. haemolyticus RTX toxin, which was similar to that produced by Enterobacteriaceae, was predicted an important virulence factor.•Concentrated culture supernatant containing RTX toxin cytolysis was attenuated by pre-incubation with anti-CD11a neutralizing antibody, suggesting that Rodentibacter sp. RTX toxin induces cell surface LFA-1 mediated cytolysins.•Experimental infection of Rodentibacter sp. intranasally with BALB/C-Rag2−/− mice showed 60% lethality and was not significantly different from that of R. pneumotropicus type strain ATCC 35149T using the log-rank test.•RTX toxin producing Rodentibacter sp. strain JRC is one of agents that requires infection prevention in laboratory rodent colonies as well as R. haemolyticus.