Characterization of a papain-like cysteine protease essential for the survival of Babesia ovis merozoites

Carletti, Tamara; Barreto, M. C.; Mesplet, María; Mira, Anabela; Weir, William; Shiels, Brian; Oliva, Abel; Schnittger, Leonhard; Florín-Christensen, Mónica

doi:10.1016/j.ttbdis.2015.09.002

Cited by 18 publications

(15 citation statements)

References 33 publications

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“…As reported in the literature, cysteine proteases are also involved in the asexual life cycle. Specifically, papain proteases play a dual role in haemoglobin digestion and parasite egress [72–74]. We identified eight B .…”

Section: Resultsmentioning

confidence: 99%

Comparative and functional genomics of the protozoan parasite Babesia divergens highlighting the invasion and egress processes

González

Estrada²,

Grande³

et al. 2019

PLoS Negl Trop Dis

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Babesiosis is considered an emerging disease because its incidence has significantly increased in the last 30 years, providing evidence of the expanding range of this rare but potentially life-threatening zoonotic disease. Babesia divergens is a causative agent of babesiosis in humans and cattle in Europe. The recently sequenced genome of B . divergens revealed over 3,741 protein coding-genes and the 10.7-Mb high-quality draft become the first reference tool to study the genome structure of B . divergens . Now, by exploiting this sequence data and using new computational tools and assembly strategies, we have significantly improved the quality of the B . divergens genome. The new assembly shows better continuity and has a higher correspondence to B . bovis chromosomes. Moreover, we present a differential expression analysis using RNA sequencing of the two different stages of the asexual lifecycle of B . divergens : the free merozoite capable of invading erythrocytes and the intraerythrocytic parasite stage that remains within the erythrocyte until egress. Comparison of mRNA levels of both stages identified 1,441 differentially expressed genes. From these, around half were upregulated and the other half downregulated in the intraerythrocytic stage. Orthogonal validation by real-time quantitative reverse transcription PCR confirmed the differential expression. A moderately increased expression level of genes, putatively involved in the invasion and egress processes, were revealed in the intraerythrocytic stage compared with the free merozoite. On the basis of these results and in the absence of molecular models of invasion and egress for B . divergens , we have proposed the identified genes as putative molecular players in the invasion and egress processes. Our results contribute to an understanding of key parasitic strategies and pathogenesis and could be a valuable genomic resource to exploit for the design of diagnostic methods, drugs and vaccines to improve the control of babesiosis.

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Section: Resultsmentioning

confidence: 99%

Comparative and functional genomics of the protozoan parasite Babesia divergens highlighting the invasion and egress processes

González

Estrada²,

Grande³

et al. 2019

PLoS Negl Trop Dis

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“…C1A falcipain-homologs bovipain, ovipain, and babesipain of B. bovis , B. ovis , and B. bigemina , respectively, have been characterized [ 31 , 32 , 33 , 34 ]. Interestingly, whereas only a single bovipain and ovipain encoding gene is present in the B. bovis and B. ovis -genome, this gene has expanded in a gene family encoding six and seven paralogs in T. parva and T. annulata , respectively [ 31 , 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

Cysteine Proteinase C1A Paralog Profiles Correspond with Phylogenetic Lineages of Pathogenic Piroplasmids

Ascencio

Florín-Christensen

Mamoun

et al. 2018

Veterinary Sciences

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Piroplasmid parasites comprising of Babesia, Theileria, and Cytauxzoon are transmitted by ticks to farm and pet animals and have a significant impact on livestock industries and animal health in tropical and subtropical regions worldwide. In addition, diverse Babesia spp. infect humans as opportunistic hosts. Molecular phylogeny has demonstrated at least six piroplasmid lineages exemplified by B. microti, B. duncani, C. felis, T. equi, Theileria sensu stricto (T. annulata, T. parva, and T. orientalis) and Babesia sensu stricto (B. bovis, B. bigemina, and B. ovis). C1A cysteine-proteinases (C1A-Cp) are papain-like enzymes implicated in pathogenic and vital steps of the parasite life cycle such as nutrition and host cell egress. An expansion of C1A-Cp of T. annulata and T. parva with respect to B. bovis and B. ovis was previously described. In the present work, C1A-Cp paralogs were identified in available genomes of species pertaining to each piroplasmid lineage. Phylogenetic analysis revealed eight C1A-Cp groups. The profile of C1A-Cp paralogs across these groups corroborates and defines the existence of six piroplasmid lineages. C. felis, T. equi and Theileria s.s. each showed characteristic expansions into extensive families of C1A-Cp paralogs in two of the eight groups. Underlying gene duplications have occurred as independent unique evolutionary events that allow distinguishing these three piroplasmid lineages. We hypothesize that C1A-Cp paralog families may be associated with the advent of the schizont stage. Differences in the invertebrate tick host specificity and/or mode of transmission in piroplasmid lineages might also be associated with the observed C1A-Cp paralog profiles.

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“…Previous studies have shown that inhibition of cysteine peptidases from apicomplexan parasites can interfere with parasite survival (Carletti et al, 2016;Okubo et al, 2007). Moreover a type 2 cystatin from H. longicornis (Hlcyst-2), found mainly in the midgut of this tick, was able to interfere with B. bovis growth in vitro (Zhou et al, 2006), demonstrating the possible interaction between cysteine peptidases from parasites with vector cystatins.…”

Section: Discussionmentioning

confidence: 78%

“…The relevance of apicomplexan cysteine peptidases for parasite survival and proliferation has already been demonstrated (Okubo et al 2007;Carletti et al 2016). Therefore, we decided to evaluate the possible inhibitory effect of different concentrations of rRmcystatin-1b on B. bovis growth, in which 50% reduction in the percentage of infected RBC was observed when compared to control-treated cultures at 72 h (Fig.…”

Section: Effect Of Rrmcystatin-1b In B Bovis Culturementioning

confidence: 99%

A novel type 1 cystatin involved in the regulation of Rhipicephalus microplus midgut cysteine proteases

Rocha

Torquato

et al. 2020

Ticks and Tick-borne Diseases

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Characterization of a papain-like cysteine protease essential for the survival of Babesia ovis merozoites

Cited by 18 publications

References 33 publications

Comparative and functional genomics of the protozoan parasite Babesia divergens highlighting the invasion and egress processes

Comparative and functional genomics of the protozoan parasite Babesia divergens highlighting the invasion and egress processes

Cysteine Proteinase C1A Paralog Profiles Correspond with Phylogenetic Lineages of Pathogenic Piroplasmids

A novel type 1 cystatin involved in the regulation of Rhipicephalus microplus midgut cysteine proteases

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