Transcriptomic analysis of Ehrlichia ruminantium during the developmental stages in bovine and tick cell culture

Tjale, Mabotse A.; Pretorius, Ashley; Josemans, Antoinette I.; Kleef, Mirinda Van; Liebenberg, Junita

doi:10.1016/j.ttbdis.2017.09.014

Cited by 9 publications

(6 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ABC transporters also are involved in uptake of ions and amino acids and may play an important role in a pathogen’s ability to infect and survive in a host cell environment 47 . The ECH_0379 mutant had low levels of transcriptional activity of the genes ECH_0517 and ECH_0972 encoding for ABC transporters, which function at different stages in the pathogenesis of infection 47 , 48 . These proteins promote the survival of pathogens in the host microenvironments 49 .…”

Section: Discussionmentioning

confidence: 99%

Impact of Three Different Mutations in Ehrlichia chaffeensis in Altering the Global Gene Expression Patterns

Kondethimmanahalli

Ganta

2018

Sci Rep

View full text Add to dashboard Cite

The rickettsial pathogen Ehrlichia chaffeensis causes a tick-borne disease, human monocytic ehrlichiosis. Mutations within certain genomic locations of the pathogen aid in understanding the pathogenesis and in developing attenuated vaccines. Our previous studies demonstrated that mutations in different genomic sites in E. chaffeensis caused variable impacts on their growth and attenuation in vertebrate and tick hosts. Here, we assessed the effect of three mutations on transcriptional changes using RNA deep-sequencing technology. RNA sequencing aided in detecting 66–80% of the transcripts of wildtype and mutant E. chaffeensis. Mutation in an antiporter gene (ECH_0379) causing attenuated growth in vertebrate hosts resulted in the down regulation of many transcribed genes. Similarly, a mutation downstream to the ECH_0490 coding sequence resulted in minimal impact on the pathogen’s in vivo growth, but caused major changes in its transcriptome. This mutation caused enhanced expression of several host stress response genes. Even though the ECH_0660 gene mutation caused the pathogen’s rapid clearance in vertebrate hosts and aids in generating a protective response, there was minimal impact on the transcriptome. The transcriptomic data offer novel insights about the impact of mutations on global gene expression and how they may contribute to the pathogen’s resistance and/or clearance from the host.

show abstract

Section: Discussionmentioning

confidence: 99%

Impact of Three Different Mutations in Ehrlichia chaffeensis in Altering the Global Gene Expression Patterns

Kondethimmanahalli

Ganta

2018

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Moreover, ERGA_CDS_03830 (homolog of ankA ) and ERGA_CDS_06440 were predicted as potential T4SS effectors for E. ruminantium using S4TE software (Meyer et al, 2013 ). In a newly published transcriptomic study on the virulent Welgevonden strain of E. ruminantium , genes encoding for T4SS components and homologs of ankA and ankB were also upregulated in EBs in comparison to RBs (Tjale et al, 2018 ). Further studies of these genes and genes encoding for T4SS components are crucial for the understanding of E. ruminantium pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Comparative Transcriptome Profiling of Virulent and Attenuated Ehrlichia ruminantium Strains Highlighted Strong Regulation of map1- and Metabolism Related Genes

Pruneau

Lebrigand

Mari

et al. 2018

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

The obligate intracellular pathogenic bacterium, Ehrlichia ruminantium, is the causal agent of heartwater, a fatal disease in ruminants transmitted by Amblyomma ticks. So far, three strains have been attenuated by successive passages in mammalian cells. The attenuated strains have improved capacity for growth in vitro, whereas they induced limited clinical signs in vivo and conferred strong protection against homologous challenge. However, the mechanisms of pathogenesis and attenuation remain unknown. In order to improve knowledge of E. ruminantium pathogenesis, we performed a comparative transcriptomic analysis of two distant strains of E. ruminantium, Gardel and Senegal, and their corresponding attenuated strains. Overall, our results showed an upregulation of gene expression encoding for the metabolism pathway in the attenuated strains compared to the virulent strains, which can probably be associated with higher in vitro replicative activity and a better fitness to the host cells. We also observed a significant differential expression of membrane protein-encoding genes between the virulent and attenuated strains. A major downregulation of map1-related genes was observed for the two attenuated strains, whereas upregulation of genes encoding for hypothetical membrane proteins was observed for the four strains. Moreover, CDS_05140, which encodes for a putative porin, displays the highest gene expression in both attenuated strains. For the attenuated strains, the significant downregulation of map1-related gene expression and upregulation of genes encoding other membrane proteins could be important in the implementation of efficient immune responses after vaccination with attenuated vaccines. Moreover, this study revealed an upregulation of gene expression for 8 genes encoding components of Type IV secretion system and 3 potential effectors, mainly in the virulent Gardel strain. Our transcriptomic study, supported by previous proteomic studies, provides and also confirms new information regarding the characterization of genes involved in E. ruminantium virulence and attenuation mechanisms.

show abstract

“…The adhesion process for E. ruminantium has not yet been elucidated, but it is hypothesized that the binding of E. ruminantium to ECs cell receptors could be done through bacterial adhesins, such as the uncharacterized protein Q5FFC8 [9,35,36], Ankyrin-like protein Q5FH29 [37], AnkA [38] or the porin-like protein Q5FGU8 [36]. The proteins AnkA and Q5FGU8 were both detected in this work, but their roles in the infection process remain unknown.…”

Section: Manipulation Of the Host Immune Response And Signaling Pathwaysmentioning

confidence: 74%

Revisiting Ehrlichia ruminantium Replication Cycle Using Proteomics: The Host and the Bacterium Perspectives

et al. 2021

View full text Add to dashboard Cite

The Rickettsiales Ehrlichia ruminantium, the causal agent of the fatal tick-borne disease Heartwater, induces severe damage to the vascular endothelium in ruminants. Nevertheless, E. ruminantium-induced pathobiology remains largely unknown. Our work paves the way for understanding this phenomenon by using quantitative proteomic analyses (2D-DIGE-MS/MS, 1DE-nanoLC-MS/MS and biotin-nanoUPLC-MS/MS) of host bovine aorta endothelial cells (BAE) during the in vitro bacterium intracellular replication cycle. We detect 265 bacterial proteins (including virulence factors), at all time-points of the E. ruminantium replication cycle, highlighting a dynamic bacterium–host interaction. We show that E. ruminantium infection modulates the expression of 433 host proteins: 98 being over-expressed, 161 under-expressed, 140 detected only in infected BAE cells and 34 exclusively detected in non-infected cells. Cystoscape integrated data analysis shows that these proteins lead to major changes in host cell immune responses, host cell metabolism and vesicle trafficking, with a clear involvement of inflammation-related proteins in this process. Our findings led to the first model of E. ruminantium infection in host cells in vitro, and we highlight potential biomarkers of E. ruminantium infection in endothelial cells (such as ROCK1, TMEM16K, Albumin and PTPN1), which may be important to further combat Heartwater, namely by developing non-antibiotic-based strategies.

show abstract

Transcriptomic analysis of Ehrlichia ruminantium during the developmental stages in bovine and tick cell culture

Cited by 9 publications

References 39 publications

Impact of Three Different Mutations in Ehrlichia chaffeensis in Altering the Global Gene Expression Patterns

Impact of Three Different Mutations in Ehrlichia chaffeensis in Altering the Global Gene Expression Patterns

Comparative Transcriptome Profiling of Virulent and Attenuated Ehrlichia ruminantium Strains Highlighted Strong Regulation of map1- and Metabolism Related Genes

Revisiting Ehrlichia ruminantium Replication Cycle Using Proteomics: The Host and the Bacterium Perspectives

Contact Info

Product

Resources

About