Comparative Genomics of the Zoonotic Pathogen Ehrlichia chaffeensis Reveals Candidate Type IV Effectors and Putative Host Cell Targets

Abstract

During infection, some intracellular pathogenic bacteria use a dedicated multiprotein complex known as the type IV secretion system to deliver type IV effector (T4E) proteins inside the host cell. These T4Es allow the bacteria to evade host defenses and to subvert host cell processes to their own advantage. Ehrlichia chaffeensis is a tick-transmitted obligate intracellular pathogenic bacterium, which causes human monocytic ehrlichiosis. Using comparative whole genome analysis, we identified the relationship between eight available E. chaffeensis genomes isolated from humans and show that these genomes are highly conserved. We identified the candidate core type IV effectome of E. chaffeensis and some conserved intracellular adaptive strategies. We assigned the West Paces strain to genetic group II and predicted the repertoires of T4Es encoded by E. chaffeensis genomes, as well as some putative host cell targets. We demonstrated that predicted T4Es are preferentially distributed in gene sparse regions of the genome. In addition to the identification of the two known type IV effectors of Anaplasmataceae, we identified two novel candidates T4Es, ECHLIB_RS02720 and ECHLIB_RS04640, which are not present in all E. chaffeensis strains and could explain some variations in inter-strain virulence. We also identified another novel candidate T4E, ECHLIB_RS02720, a hypothetical protein exhibiting EPIYA, and NLS domains as well as a classical type IV secretion signal, suggesting an important role inside the host cell. Overall, our results agree with current knowledge of Ehrlichia molecular pathogenesis, and reveal novel candidate T4Es that require experimental validation. This work demonstrates that comparative effectomics enables identification of important host pathways targeted by the bacterial pathogen. Our study, which focuses on the type IV effector repertoires among several strains of E. chaffeensis species, is an original approach and provides rational putative targets for the design of alternative therapeutics against intracellular pathogens. The collection of putative effectors of E. chaffeensis described in our paper could serve as a roadmap for future studies of the function and evolution of effectors.

Ehrlichia ruminantiumuses its transmembrane protein Ape to adhere to host bovine aortic endothelial cells

“…These integrated approaches led to the effective identification of several bacterial virulence determinants (e.g. effectors and regulators) and their diverse mechanisms of action (Cheng et al, 2008;Rikihisa, 2017;Marcelino et al, 2015b ;Moumene et al, 2017;Noroy and Meyer, 2017;Noroy and Meyer, 2021). Notably, Rikihisa et al identified that the EtpE protein governs the binding and entry of E. chaffeensis into its host cells (Mohan Kumar et al, 2013).…”

Comparative genomic analysis of Ralstonia solanacearum reveals candidate avirulence effectors in HA4-1 triggering wild potato immunity

“…With the rapid increase in high-quality genomes, the application of comparative genomics is more and more extensive and in-depth (Setubal et al, 2018). So far, comparative genomics has been used in various species such as the Zoonotic pathogen Ehrlichia chaffeensis, revealing candidate effectors and putative host cell targets (Noroy and Meyer, 2017). The complete genome of seven highly virulent Xanthomonas.…”

The super repertoire of type IV effectors in the pangenome ofEhrlichiaspp. provides insights into host-specificity and pathogenesis

“…Liberty. This effector appears to be involved in the differential inter-strain virulence observed between Arkansas and Liberty strains in SCID mice (Noroy and Meyer, 2016). Moreover, some intense recombination events between E. ruminantium strains have been discovered, which may facilitate bacterial adaptation for survival and adaptation under various environmental conditions in both vector and host species (Cangi et al, 2016).…”