Regardless of the severity of CDI induced by HMX-149, HMX-152, and HSJD-312, their isolation from clinical cases along with the unusual conformation and location of their PaLoc suggest that the minimum requirement for the induction of these infections is the ability to secrete at least one toxin targeting small GTPases of the Rho family. The gene discussed is RHO; the disease is clostridium difficile infection.