Ehrlichia type IV secretion effector ECH0825 is translocated to mitochondria and curbs ROS and apoptosis by upregulating host MnSOD

Liu, Hongyan; Bao, Weichao; Lin, Mingqun; Niu, Hua; Rikihisa, Yasuko

doi:10.1111/j.1462-5822.2012.01775.x

Cited by 90 publications

(140 citation statements)

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“…Ehrlichia spp. other than E. canis have been shown to decrease reactive oxygen species capable of destroying intracellular pathogens, and inhibiting monocyte death by apoptosis (Liu et al, 2012). Both of these mechanisms potentially facilitate longer intracellular pathogen survival, nevertheless, other mechanisms may be involved in H. canis and E. canis co-infection.…”

Section: Discussionmentioning

confidence: 98%

Canine vector-borne co-infections: Ehrlichia canis and Hepatozoon canis in the same host monocytes

Baneth

Harrus

Gal

et al. 2015

Veterinary Parasitology

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Section: Discussionmentioning

confidence: 98%

Canine vector-borne co-infections: Ehrlichia canis and Hepatozoon canis in the same host monocytes

Baneth

Harrus

Gal

et al. 2015

Veterinary Parasitology

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“…However, Liu et al found that mitochondrial biochemical activity was reduced, as evidenced from the measurement of mitochondrial DNA synthesis or the transcription of several mitochondrial genes (37). There is also evidence that the E. chaffeensis type IV secretion system is used to insert bacterial effector proteins into host mitochondria (36). These observations suggest that the organism inhibits mitochondrial activity, perhaps to inhibit the generation of mitochondrially produced oxidative products that would be harmful to the bacteria (5,68).…”

Section: Discussionmentioning

confidence: 99%

Identification of Critical Host Mitochondrion-Associated Genes during Ehrlichia chaffeensis Infections

et al. 2012

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bEhrlichia chaffeensis is an obligate intracellular bacterium that causes human monocytic ehrlichiosis (HME). To determine what host components are important for bacterial replication, we performed microarray analysis on Drosophila melanogaster S2 cells by comparing host gene transcript levels between permissive and nonpermissive conditions for E. chaffeensis growth. Five-hundred twenty-seven genes had increased transcript levels unique to permissive growth conditions 24 h postinfection. We screened adult flies that were mutants for several of the "permissive" genes for the ability to support Ehrlichia replication. Three additional D. melanogaster fly lines with putative mutations in pyrimidine metabolism were also tested. Ten fly lines carrying mutations in the genes CG6479, separation anxiety, chitinase 11, CG6364 (Uck2), CG6543 (Echs1), withered (whd), CG15881 (Ccdc58), CG14806 (Apop1), CG11875 (Nup37), and dumpy (dp) had increased resistance to infection with Ehrlichia. Analysis of RNA by quantitative real-time reverse transcription-PCR (qRT-PCR) confirmed that the bacterial load was decreased in these mutant flies compared to wild-type infected control flies. Seven of these genes (san, Cht11, Uck2, Echs1, whd, Ccdc58, and Apop1) encoded proteins that had mitochondrial functions or could be associated with proteins with mitochondrial functions. Treatment of THP-1 cells with double-stranded RNA to silence the human UCK2 gene indicates that the disruption of the uridine-cytidine kinase affects E. chaffeensis replication in human macrophages. Experiments with cyclopentenyl cytosine (CPEC), a CTP synthetase inhibitor and cytosine, suggest that the nucleotide salvage pathway is essential for E. chaffeensis replication and that it may be important for the provision of CTP, uridine, and cytidine nucleotides. Ehrlichia chaffeensis is the causative agent of human monocytic ehrlichiosis (HME). There were 1,429 cases of HME in 2010 and 2011 (14). This represents a significant increase in the incidence of the disease since 2003 and qualifies HME as an emerging infectious disease (25). In addition to being reported in the United States, HME has also been documented in Africa, Europe, China, and Brazil (9,16,42,67). E. chaffeensis is an obligate intracellular bacterium. However, little is known about the parasitized-host requirements for bacterial replication.Drosophila melanogaster has been used to study a variety of intracellular pathogens. In particular, it has been successfully manipulated for the identification of genes involved in host-pathogen interactions. These pathogens include Listeria monocytogenes (1, 2), Chlamydia trachomatis (20), Mycobacterium marinum (1, 18, 30, 48), Francisella tularensis (51, 64), and the protozoan parasite Plasmodium gallinaceum (8,53).We previously demonstrated that E. chaffeensis is capable of infecting, completing its life cycle, and maintaining its pathogenicity in both Drosophila S2 cells (39) and adult flies (40). We have also identified growth conditions that were nonpermissiv...

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“…marginale (Lockwood et al ., 2011) and E . chaffeensis (Rikihisa & Lin, 2010, Liu et al ., 2012) . To our knowledge, only two of these effectors have been shown to directly interact with their cognate RvhD4 proteins: Ats-1 of A .…”

Section: Sec-independent Secretory Pathwaysmentioning

confidence: 99%

“…phagocytophilum (Niu et al ., 2010) and ECH0825 of E . chaffeensis (Liu et al ., 2012) . All other rvh substrates, including the well-characterized AnkA effector, were shown to be translocated by heterologous T4SSs from either A .…”

Section: Sec-independent Secretory Pathwaysmentioning

confidence: 99%

Secretome of obligate intracellularRickettsia

et al. 2014

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The genus Rickettsia (Alphaproteobacteria; Rickettsiales; Rickettsiaceae) is comprised of obligate intracellular parasites, with virulent species of interest both as causes of emerging infectious diseases and for their potential deployment as bioterrorism agents. Currently there are no effective commercially available vaccines, with treatment limited primarily to tetracycline antibiotics, though others (e.g., josamycin, ciprofloxacin, chloramphenicol and azithromycin) are also effective. Much of the recent research geared towards understanding mechanisms underlying rickettsial pathogenicity has centered on characterization of secreted proteins that directly engage eukaryotic cells. Herein, we review all aspects of the Rickettsia secretome, including six secretion systems, 19 characterized secretory proteins, and potential moonlighting proteins identified on surfaces of multiple Rickettsia species. Employing bioinformatics and phylogenomics, we present novel structural and functional insight on each secretion system. Unexpectedly, our investigation revealed that the majority of characterized secretory proteins have not been assigned to their cognate secretion pathways. Furthermore, for most secretion pathways, the requisite signal sequences mediating translocation are poorly understood. As a blueprint for all known routes of protein translocation into host cells, this resource will assist research aimed at uniting characterized secreted proteins with their apposite secretion pathways. Furthermore, our work will help in the identification of novel secreted proteins involved in rickettsial “life on the inside”.

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Ehrlichia type IV secretion effector ECH0825 is translocated to mitochondria and curbs ROS and apoptosis by upregulating host MnSOD

Cited by 90 publications

References 88 publications

Canine vector-borne co-infections: Ehrlichia canis and Hepatozoon canis in the same host monocytes

Canine vector-borne co-infections: Ehrlichia canis and Hepatozoon canis in the same host monocytes

Identification of Critical Host Mitochondrion-Associated Genes during Ehrlichia chaffeensis Infections

Secretome of obligate intracellularRickettsia

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