Chapter 4 Peptidases of Trematodes

Kašný, Martin; Mikeš, Libor; Hampl, Vladimı́r; Dvořák, Jan; Caffrey, Conor R.; Dalton, John P.; Horák, Petr

doi:10.1016/s0065-308x(09)69004-7

Cited by 71 publications

(52 citation statements)

References 304 publications

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“…Furthermore, recent advances in proteomic analyses of schistosomes have revealed that peptidases are one of the main virulence factors involved in the pathogenesis of schistosomiasis (McKerrow et al 2006, Kasný et al 2009. In this work, we performed a phylogenomic analysis to address the two main questions of (i) whether peptidase families are expanded in the S. mansoni proteome and (ii) whether they share similar evolutionary histories.…”

Section: Resultsmentioning

confidence: 99%

“…Whether gene fusion/fission also plays a role in the evolution of the S. mansoni genome will be a subject of a future work. Our previous study indicated that domain shuffling is one of the main evolutionary forces driving the sequence and functional diversification of the protein kinases of this parasite (Andrade et al 2011, Avelar et al 2011.Peptidases have been implicated in various processes that are crucial to the development and survival of parasites, including host invasion, degradation of haemoglobin in blood feeding, immune evasion and activation of inflammation (McKerrow et al 2006, Kasný et al 2009). …”

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confidence: 98%

“…Our results indicate that each peptidase family has a unique evolutionary history within/across the analysed species. Furthermore, our data support the hypothesis that gene duplication events followed by divergence is the main mechanism shaping the evolution of S. mansoni-specific paralogous groups.The analysis of the evolutionary histories of these three S. mansoni families is relevant to functional genomics, evolutionary biology, medicine and biotechnology, especially taking into account the importance of S. mansoni peptidases in the development of schistosomiasis and that they have been described as promising vaccine and drug targets (McKerrow et al 2006, Abdulla et al 2007, Kasný et al 2009). This dataset is particularly rich in metazoans (76% of the selected species) that cover important evolutionary innovations, for example, the origin of bilateral symmetry, the third germ layer, the development of organs, systems, complex patterns of communication and the emergence of the adaptive immune system, which makes it especially suitable for addressing the evolutionary innovations in S. mansoni in comparison with other metazoan species (phylomedb.org).…”

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confidence: 99%

“…Peptidases have been implicated in various processes that are crucial to the development and survival of parasites, including host invasion, degradation of haemoglobin in blood feeding, immune evasion and activation of inflammation (McKerrow et al 2006, Kasný et al 2009). …”

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confidence: 99%

“…Over the past several years, advances in the molecular analysis of major parasites have identified some key factors involved in parasitic diseases and peptidases as one of the major factors of pathogenicity (McKerrow et al 2006, Kasný et al 2009). These enzymes have been implicated in processes that are crucial to the development and survival of helminth parasites, including digestion, invasion from host tissues, activation of inflammation and evasion of the host immune system (McKerrow et al 2006, Kasný et al 2009).…”

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Evolutionary histories of expanded peptidase families in Schistosoma mansoni

Silva

Marcet‐Houben

Zerlotini

et al. 2011

Mem. Inst. Oswaldo Cruz

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Schistosoma mansoni is one of the three main causative agents of human schistosomiasis, a major health problem with a vast socio-economic impact. Recent advances in the proteomic analysis of schistosomes have revealed that peptidases are the main virulence factors involved in the pathogenesis of this disease. In this context, evolutionary studies can be applied to identify peptidase families that have been expanded in genomes over time in response to different selection pressures. Using a phylogenomic approach, we searched for expanded endopeptidase families in the S. mansoni predicted proteome with the aim of contributing to the knowledge of such enzymes as potential therapeutic targets. We found three endopeptidase families that comprise leishmanolysins (metallopeptidase M8 family), cercarial elastases (serine peptidase S1 family) and cathepsin D proteins (aspartic peptidase A1 family). Our results suggest that the Schistosoma members of these families originated from successive gene duplication events in the parasite lineage after its diversification from other metazoans. Overall, critical residues are conserved among the duplicated genes/proteins. Furthermore, each protein family displays a distinct evolutionary history. Altogether, this work provides an evolutionary view of three S. mansoni peptidase families, which allows for a deeper understanding of the genomic complexity and lineage-specific adaptations potentially related to the parasitic lifestyle.Key words: phylogenomics -maximum likelihood analysis -homology predictionfunctional annotation -proteases -paralogous families -parasite genomics S. mansoni peptidase families • Larissa Lopes Silva et al. 865et al. 2010). In general, cysteine peptidases have cysteine and histidine residues forming their "catalytic dyad". Meanwhile, other active site residues have been found. Glutamic peptidases have glutamic acid residues as their primary catalytic residues, which are probably the nucleophilic attack mediators involved in the catalysis (Fujinaga et al. 2004, Rawlings et al. 2010. In metallopeptidases, the catalytic mechanism usually involves a single catalytic zinc ion tetrahedrally coordinated by one glutamate and two histidine residues (Rawlings et al. 2010). Serine peptidases have serine residues at their active sites, which together with two other variable amino acids constitute the "catalytic triad" (Hedstrom 2002, Rawlings et al. 2010. Threonine peptidases have threonine residues as their nucleophiles during catalysis. For unknown peptidases, the active site residues have not yet been determined. Evolutionary analyses have been applied to a broad range of studies, which include the identification of gene/protein families that have expanded in a specific lineage over evolutionary time and possibly indicate the existence of selective pressure (Irving et al. 2003, Sargeant et al. 2006, Nahum & Pereira 2008, Robinson et al. 2008, Wu et al. 2009, Huzurbazar et al. 2010. The availability of faster and more powerful computers combined with the development of...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Evolutionary histories of expanded peptidase families in Schistosoma mansoni

Silva

Marcet‐Houben

Zerlotini

et al. 2011

Mem. Inst. Oswaldo Cruz

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The Phylogeny, Structure and Function of Trematode Cysteine Proteases, with Particular Emphasis on the Fasciola hepatica Cathepsin L Family

Stack

Dalton

Robinson

2011

Advances in Experimental Medicine and Biology

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Helminth parasites (nematodes, flatworms and cestodes) infect over 1 billion of the world's population causing high morbidity and mortality. The large tissue-dwelling worms express papain-like cysteine peptidases, termed cathepsins that play important roles in virulence including host entry, tissue migration and the suppression of host immune responses. Much of our knowledge of helminth cathepsins comes from studies using flatworms or trematode (fluke) parasites. The developmentally-regulated expression of these proteases correlates with the passage of parasites through host tissues and their encounters with different host macromolecules. Recent phylogenetic, biochemical and structural studies indicate that trematode cathepsins exhibit overlapping but distinct substrate specificities due to divergence within the protease active site. Here we provide an overview of the evolution, biochemistry and structure of these important enzymes and highlight how recent advances in proteomics and gene silencing techniques are allowing researchers to probe their biological functions. We focus mainly on members of the cathepsin L gene family of the animal and human pathogen, Fasciola hepatica, because of our deep understanding of their function, biochemistry and structure.

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Cathepsins B1 and B2 of Trichobilharzia SPP., Bird Schistosomes Causing Cercarial Dermatitis

Kašný

Mikeš

Dolečková

et al. 2011

Advances in Experimental Medicine and Biology

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Trichobilharzia regenti and T. szidati are schistosomes that infect birds. although T. regenti/T. szidati can only complete their life cycle in specific bird hosts (waterfowl), their larvae-cercariae are able to penetrate, transform and then migrate as schistosomula in nonspecific hosts (e.g., mouse, man). Peptidases are among the key molecules produced by these schistosomes that enable parasite invasion and survival within the host and include cysteine peptidases such as cathepsins B1 and B2. These enzymes are indispensable bio-catalysts in a number of basal biological processes and host-parasite interactions, e.g., tissue invasion/migration, nutrition and immune evasion. Similar biochemical and functional characteristics were observed for cathepsins B1 and B2 in bird schistosomes (T. regenti, T. szidati) and also for their homologs in human schistosomes (Schistosoma mansoni, S. japonicum). Therefore, data obtained in the research of bird schistosomes can also be exploited for the control of human schistosomes such as the search for targets of novel chemotherapeutic drugs and vaccines.

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Chapter 4 Peptidases of Trematodes

Cited by 71 publications

References 304 publications

Evolutionary histories of expanded peptidase families in Schistosoma mansoni

Evolutionary histories of expanded peptidase families in Schistosoma mansoni

The Phylogeny, Structure and Function of Trematode Cysteine Proteases, with Particular Emphasis on the Fasciola hepatica Cathepsin L Family

Cathepsins B1 and B2 of Trichobilharzia SPP., Bird Schistosomes Causing Cercarial Dermatitis

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