The Recent Evolution of a Maternally-Inherited Endosymbiont of Ticks Led to the Emergence of the Q Fever Pathogen, Coxiella burnetii

Q fever is a highly infectious disease with a worldwide distribution. Its causative agent, the intracellular bacterium Coxiella burnetii, infects a variety of vertebrate species, including humans. Its evolutionary origin remains almost entirely unknown and uncertainty persists regarding the identity and lifestyle of its ancestors. A few tick species were recently found to harbor maternally-inherited Coxiella-like organisms engaged in symbiotic interactions, but their relationships to the Q fever pathogen remain unclear. Here, we extensively sampled ticks, identifying new and atypical Coxiella strains from 40 of 58 examined species, and used this data to infer the evolutionary processes leading to the emergence of C. burnetii. Phylogenetic analyses of multi-locus typing and whole-genome sequencing data revealed that Coxiella-like organisms represent an ancient and monophyletic group allied to ticks. Remarkably, all known C. burnetii strains originate within this group and are the descendants of a Coxiella-like progenitor hosted by ticks. Using both colony-reared and field-collected gravid females, we further establish the presence of highly efficient maternal transmission of these Coxiella-like organisms in four examined tick species, a pattern coherent with an endosymbiotic lifestyle. Our laboratory culture assays also showed that these Coxiella-like organisms were not amenable to culture in the vertebrate cell environment, suggesting different metabolic requirements compared to C. burnetii. Altogether, this corpus of data demonstrates that C. burnetii recently evolved from an inherited symbiont of ticks which succeeded in infecting vertebrate cells, likely by the acquisition of novel virulence factors.
Author Summary How virulent infectious diseases emerge from non-pathogenic organisms is a challenging question. Here, we address this evolutionary issue in the case of Q fever. Its causative agent, the intracellular bacterium Coxiella burnetii, is extremely infectious to humans and a variety of animals. However, uncertainty persists regarding its evolutionary origin, including the identity and lifestyle of its ancestors. In this article, we show that C. burnetii arose from a rare evolutionary transformation of a maternally-inherited endosymbiont of ticks into a specialized and virulent pathogen of vertebrates. While arthropod symbionts are typically transmitted maternally and thought not to be infectious to vertebrates, we establish here that one Coxiella symbiont has evolved the necessary adaptations to exploit the vertebrate cell, leading to the emergence of Q fever.