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

Abstract

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.

Host and Bacterial Factors Control Susceptibility of Drosophila melanogaster to Coxiella burnetii Infection

“…Other animal and avirulent bacterial models, particularly those suitable for BSL2, represent safer alternatives to investigate how host and bacterial factors interface and affect the pathogenesis of C. burnetii. Here, we present Drosophila as a genetically tractable host model to study Coxiella infection that complements previous work performed in mammalian and other invertebrate models (23)(24)(25). The malleability of the C. elegans and Drosophila models makes them applicable to studies in mammalian systems, and Drosophila can be used to identify novel arthropod genetic variants implicated in susceptibility to C. burnetii infection that have homologous mammalian counterparts.…”

“…Although C. burnetii has been detected in tick populations worldwide (19)(20)(21), the role of ticks in the epidemiology of Q fever remains unclear (22). A recent study demonstrated that C. burnetii has emerged from Coxiellalike endosymbiont organisms found in ticks, revealing evidence of how the bacterium evolved from arthropods to infect mammalian cells by the acquisition of virulence factors (23). Another study used larvae of the greater wax moth, Galleria mellonella, to investigate antibiotic efficacy following Coxiella infection and the role of dotA/dotB, two components of the Coxiella T4SS, in establishing infection (24).…”

Molecular Detection and Genotyping of Coxiella-Like Endosymbionts in Ticks that Infest Horses in South Korea

“…The phylogenetic origin of C . burnetii is unknown, but new Coxiella -like endosymbionts (CLE) have been isolated from ticks [4, 5]. CLE differ from C .…”

Emerging Horizons for Tick-Borne Pathogens: From the ‘One Pathogen–one Disease’ Vision to the Pathobiome Paradigm

“…Adding further complexity, some authors consider Rickettsia species as endosymbionts that are transmitted vertically in arthropods, and only secondarily serve as pathogens of vertebrates [40]. For the Coxiella genus, the species C. burnetii is mostly considered as a vertebrate pathogen while numerous other Coxiella species have been found associated to ticks [41]. Phylogenetic analyses combined with future science group www.futuremedicine.com experimental approaches suggested that these might also be considered as endosymbionts of ticks [11,42].…”