Ehrlichia's molecular tricks to manipulate their host cells

Moumène, Amal; Meyer, Damien

doi:10.1016/j.micinf.2015.11.001

Cited by 24 publications

(25 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In summary, our results are in accordance with the current knowledge of Ehrlichia molecular pathogenesis (Moumène and Meyer, 2016), and the T4Es we predicted using the S4TE algorithm for E. chaffeensis are good candidates for further biological analysis. In addition, the human interactome predicted via HPIDB provides useful information on the possible mode of action of these putative T4Es within the host cell.…”

Section: Discussionsupporting

confidence: 91%

“…Because type IV effector repertoires are suggested to be major determinants of virulence in Ehrlichia (Moumène and Meyer, 2016), it is also important to understand the diversity of type IV effectors present in different species that infect common hosts. Likewise, studying the evolution of type IV effector repertoires among different bacterial species with different host ranges or lifestyles could provide key information to identify the determinants of host specificity.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Noroy

Meyer

2017

Front. Cell. Infect. Microbiol.

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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

Noroy

Meyer

2017

Front. Cell. Infect. Microbiol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Orientia is able to infect a range of cell types, including endothelial, fibroblast, monocyte/macrophage and dendritic cells (Moron et al, 2001;Paris et al, 2012;Keller et al, 2014). Similar to the other Rickettsiaceae, but in contrast to the Chlamydia and Anaplasmataceae that live within remodelled vacuoles (Bastidas et al, 2013;Moumè ne and Meyer, 2016), Orientia escapes from the endo-lysosomal pathway shortly after infection and replicates freely in the host cell cytoplasm (Chu et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Evidence for a peptidoglycan‐like structure in Orientia tsutsugamushi

Atwal

Giengkam

Chaemchuen

et al. 2017

Molecular Microbiology

View full text Add to dashboard Cite

Summary Bacterial cell walls are composed of the large cross-linked macromolecule peptidoglycan, which maintains cell shape and is responsible for resisting osmotic stresses. This is a highly conserved structure and the target of numerous antibiotics. Obligate intracellular bacteria are an unusual group of organisms that have evolved to replicate exclusively within the cytoplasm or vacuole of a eukaryotic cell. They tend to have reduced amounts of peptidoglycan, likely due to the fact that their growth and division takes place within an osmotically protected environment, and also due to a drive to reduce activation of the host immune response. Of the two major groups of obligate intracellular bacteria, the cell wall has been much more extensively studied in the Chlamydiales than the Rickettsiales. Here, we present the first detailed analysis of the cell envelope of an important but neglected member of the Rickettsiales, Orientia tsutsugamushi. This bacterium was previously reported to completely lack peptidoglycan, but here we present evidence supporting the existence of a peptidoglycan-like structure in Orientia, as well as an outer membrane containing a network of cross-linked proteins, which together confer cell envelope stability. We find striking similarities to the unrelated Chlamydiales, suggesting convergent adaptation to an obligate intracellular lifestyle.

show abstract

“…A pathogen such as Ehrlichia , uses tightly regulated pathogenicity determinants to hijack host cellular processes and replicate inside the cell (extensively reviewed in Moumène and Meyer, 2016). Thus, the invasion of the cell requires bacterial adhesion to a specific receptor.…”

Section: Introductionmentioning

confidence: 99%

Economic Game Theory to Model the Attenuation of Virulence of an Obligate Intracellular Bacterium

Tago

Meyer

2016

Front. Cell. Infect. Microbiol.

Self Cite

View full text Add to dashboard Cite

Diseases induced by obligate intracellular pathogens have a large burden on global human and animal health. Understanding the factors involved in the virulence and fitness of these pathogens contributes to the development of control strategies against these diseases. Based on biological observations, a theoretical model using game theory is proposed to explain how obligate intracellular bacteria interact with their host. The equilibrium in such a game shows that the virulence and fitness of the bacterium is host-triggered and by changing the host's defense system to which the bacterium is confronted, an evolutionary process leads to an attenuated strain. Although, the attenuation procedure has already been conducted in practice in order to develop an attenuated vaccine (e.g., with Ehrlichia ruminantium), there was a lack of understanding of the theoretical basis behind this process. Our work provides a model to better comprehend the existence of different phenotypes and some underlying evolutionary mechanisms for the virulence of obligate intracellular bacteria.

show abstract

Ehrlichia's molecular tricks to manipulate their host cells

Cited by 24 publications

References 50 publications

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

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

Evidence for a peptidoglycan‐like structure in Orientia tsutsugamushi

Economic Game Theory to Model the Attenuation of Virulence of an Obligate Intracellular Bacterium

Contact Info

Product

Resources

About