Thiol-Based Posttranslational Modifications in Parasites

Jortzik, Esther; Wang, Lihui; Becker, Katja

doi:10.1089/ars.2011.4266

Cited by 24 publications

(19 citation statements)

References 259 publications

(225 reference statements)

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“…The E. granulosus genome had 48 DLC members (compared to 35 in Schistosoma japonicum and 29 in Schistosoma mansoni), whereas 4-7 were found in the 4 nematodes. We identified 49 cadherins in the E. granulosus genome, similar to the numbers found in schistosomes (51-65) but more than in nematodes (12)(13)(14)(15)(16)(17)(18) (Supplementary Table 22b). Cadherins belong to a class of type 1 transmembrane proteins that have important roles in cell recognition and adhesion.…”

Section: Domain Families Gained In E Granulosussupporting

confidence: 67%

“…granulosus and the other parasitic worms encode a special orthologous group of prenylcysteine oxidases (EG_06057), which may catalyze the final step in the degradation of prenylated proteins. Protein prenylation has been studied extensively in parasites, with prenyltransferase inhibitors found to inhibit the differentiation and growth of several species 18 . Prenyltransferase is a key enzyme in the biosynthesis of prenylated proteins and, along with prenylcysteine oxidase, may represent a novel drug target.…”

Section: Orthologs In Parasitic Helminths As Potential Intervention Tmentioning

confidence: 99%

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The genome of the hydatid tapeworm Echinococcus granulosus

et al. 2013

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A r t i c l e sThe dog tapeworm E. granulosus is one of a group of medically important parasitic helminths of the family Taeniidae (Platyhelminthes; Cestoda; Cyclophyllidea) that infect at least 50 million people globally 1 . Its life cycle involves two mammals, including an intermediate host, usually a domestic or wild ungulate (humans are accidental intermediate hosts) and a canine-definitive host, such as the domestic dog. The larval (metacestode) stage causes hydatidosis (cystic hydatid disease; cystic echinococcosis), a chronic cyst-forming disease in the intermediate (human) host. Currently, up to 3 million people are infected with E. granulosus 2,3 , and, in some areas, 10% of the population has detectable hydatid cysts by abdominal ultrasound and chest X-ray 4,5 .E. granulosus has no gut, circulatory or respiratory organs. It is monoecious, producing diploid eggs that give rise to ovoid embryos, the oncospheres. Strobilization is a notable feature of cestode biology, whereby proglottids bud distally from the anterior scolex, resulting in the production of tandem reproductive units exhibiting increasing degrees of development. A unique characteristic of the larvae (protoscoleces, PSCs) within the hydatid cyst is an ability to develop bidirectionally into an adult worm in the dog gastrointestinal tract or into a secondary hydatid cyst in the intermediate (human) host, a process triggered by bile acids 6 . Another distinct feature of E. granulosus is its capacity to infect and adapt to a large number of mammalian species as intermediate hosts, which has contributed to its cosmopolitan global distribution.Here we report the sequence and analysis of the E. granulosus genome. Comprising nine pairs of chromosomes 7 , it is one of the first cestode genomes to be sequenced and complements the recent publication by Tsai et al. 8 of a high-quality genome for Echinococcus multilocularis (the cause of alveolar echinococcosis), together with draft genomes of three other tapeworm species including E. granulosus. Our study provides insights into the biology, development, differentiation, evolution and host interaction of E. granulosus and has identified a range of drug and vaccine targets that can facilitate the development of new intervention tools for hydatid treatment and control. Cystic echinococcosis (hydatid disease), caused by the tapeworm E. granulosus, is responsible for considerable human morbidity and mortality. This cosmopolitan disease is difficult to diagnose, treat and control. We present a draft genomic sequence for the worm comprising 151.6 Mb encoding 11,325 genes. Comparisons with the genome sequences from other taxa show that E. granulosus has acquired a spectrum of genes, including the EgAgB family, whose products are secreted by the parasite to interact and redirect host immune responses. We also find that genes in bile salt pathways may control the bidirectional development of E. granulosus, and sequence differences in the calcium channel subunit EgCa v b 1 may be associated with praziquantel sens...

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Section: Domain Families Gained In E Granulosussupporting

confidence: 67%

Section: Orthologs In Parasitic Helminths As Potential Intervention Tmentioning

confidence: 99%

The genome of the hydatid tapeworm Echinococcus granulosus

et al. 2013

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“…As a highly membrane-permeable molecule, NO diffuses easily across cell membranes and enters parasite cells, where it is quickly oxidized to RNS, especially in the presence of a high flux of reactive oxygen species (ROS) within the parasites (6,21). A compelling feature of RNS is to induce SNO (18).…”

Section: Discussionmentioning

confidence: 99%

Protein S-nitrosylation in Plasmodium falciparum

Wang

Delahunty

Prieto

et al. 2014

Antioxidants & Redox Signaling

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“…The oxidation of protein thiols may cause changes in protein structure and activity and can control redox signaling pathways. In eukaryotes, S-glutathionylation is an important redox-regulatory thiol modification, and numerous proteins have been identified as S-glutathionylated using large-scale redox proteomics studies (7,22,23,26). S-glutathionylation serves to protect critical Cys residues against overoxidation and acts as a mechanism for the redox control of protein function in eukaryotes and some bacteria (7).…”

Section: Introductionmentioning

confidence: 99%

Redox Regulation in Bacillus subtilis: The Bacilliredoxins BrxA(YphP) and BrxB(YqiW) Function in De-Bacillithiolation of S-Bacillithiolated OhrR and MetE

Gaballa

Khanh

Roberts

et al. 2014

Antioxidants & Redox Signaling

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Aims: In bacillithiol (BSH)-utilizing organisms, protein S-bacillithiolation functions as a redox switch in response to oxidative stress and protects critical Cys residues against overoxidation. In Bacillus subtilis, both the redox-sensing repressor OhrR and the methionine synthase MetE are redox controlled by S-bacillithiolation in vivo. Here, we identify pathways of protein de-bacillithiolation and test the hypothesis that YphP(BrxA) and YqiW(BrxB) act as bacilliredoxins (Brx) to remove BSH from OhrR and MetE mixed disulfides. Results: We present evidence that the BrxA and BrxB paralogs have de-bacillithiolation activity. This Brx activity results from attack of the amino-terminal Cys residue in a CGC motif on protein BSH-mixed disulfides. B. subtilis OhrR DNA-binding activity is eliminated by S-thiolation on its sole Cys residue. Both the BrxA and BrxB bacilliredoxins mediate de-bacillithiolation of OhrR accompanied by the transfer of BSH to the amino-terminal cysteine of their CGC active site motif. In vitro studies demonstrate that BrxB can restore DNA-binding activity to OhrR which is S-bacillithiolated, but not to OhrR that is S-cysteinylated. MetE is most strongly S-bacillithiolated at Cys719 in vitro and can be efficiently de-bacillithiolated by both BrxA and BrxB. Innovation and Conclusion: We demonstrate that BrxA and BrxB function in the reduction of BSH mixed protein disulfides with two natural substrates (MetE, OhrR). These results provide biochemical evidence for a new class of bacterial redox-regulatory proteins, the bacilliredoxins, which function analogously to glutaredoxins. Bacilliredoxins function in concert with other thiol-disulfide oxidoreductases to maintain redox homeostasis in response to disulfide stress conditions. Antioxid. Redox Signal. 21, 357-367.

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Thiol-Based Posttranslational Modifications in Parasites

Abstract: The in vivo regulation of cysteine modifications and their role in parasite development will be of great interest in order to understand redox signaling in parasites.

Cited by 24 publications

References 259 publications

The genome of the hydatid tapeworm Echinococcus granulosus

The genome of the hydatid tapeworm Echinococcus granulosus

Protein S-nitrosylation in Plasmodium falciparum

Redox Regulation in Bacillus subtilis: The Bacilliredoxins BrxA(YphP) and BrxB(YqiW) Function in De-Bacillithiolation of S-Bacillithiolated OhrR and MetE

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