Comparative Genomics of the Zoonotic PathogenEhrlichia chaffeensisReveals Candidate Type IV Effectors and Putative Host Cell Targets.
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 chaffeensisis a tick-transmitted obligate intracellular pathogenic bacterium, which causes human monocytic ehrlichiosis. Using comparative whole genome analysis, we identified the relationship between eight availableE. chaffeensisgenomes isolated from humans and show that these genomes are highly conserved. We identified the candidate core type IV effectome ofE. chaffeensisand some conserved intracellular adaptive strategies. We assigned the West Paces strain to genetic group II and predicted the repertoires of T4Es encoded byE. chaffeensisgenomes, 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 ofAnaplasmataceae, we identified two novel candidates T4Es, ECHLIB_RS02720 and ECHLIB_RS04640, which are not present in allE. chaffeensisstrains 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 ofEhrlichiamolecular 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 ofE. chaffeensisspecies, is an original approach and provides rational putative targets for the design of alternative therapeutics against intracellular pathogens. The collection of putative effectors ofE. chaffeensisdescribed in our paper could serve as a roadmap for future studies of the function and evolution of effectors.
CIRAD, UMR ASTREGuadeloupe, France; INRA, UMR 1309 ASTREMontpellier, France; Université des AntillesGuadeloupe, France.
Christophe
C
Noroy
CIRAD, UMR ASTREGuadeloupe, France; INRA, UMR 1309 ASTREMontpellier, France.
Damien F
DF
Meyer
D018469:Ehrlichia chaffeensis / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D016873:Ehrlichiosis / Q000382:microbiology; D016680:Genome, Bacterial; D023281:Genomics; D005838:Genotype; D054884:Host-Pathogen Interactions; D006801:Humans; D000069319:Type IV Secretion Systems / Q000235:genetics*; D037521:Virulence Factors / Q000235:genetics*
D000069319:Type IV Secretion Systems; D037521:Virulence Factors
Ehrlichia chaffeensis; comparative genomics; genome plasticity; host-pathogen interactions; type IV effectors