Dataset Information

Investigation of the proteolytic functions of an expanded cercarial elastase gene family in Schistosoma mansoni.

ABSTRACT: Cercarial elastase is the major invasive larval protease in Schistosoma mansoni, a parasitic blood fluke, and is essential for host skin invasion. Genome sequence analysis reveals a greatly expanded family of cercarial elastase gene isoforms in Schistosoma mansoni. This expansion appears to be unique to S. mansoni, and it is unknown whether gene duplication has led to divergent protease function.Profiling of transcript and protein expression patterns reveals that cercarial elastase isoforms are similarly expressed throughout the S. mansoni life cycle. Computational modeling predicts key differences in the substrate-binding pockets of various cercarial elastase isoforms, suggesting a diversification of substrate preferences compared with the ancestral gene of the family. In addition, active site labeling of SmCE reveals that it is activated prior to exit of the parasite from its intermediate snail host.The expansion of the cercarial gene family in S. mansoni is likely to be an example of gene dosage. In addition to its critical role in human skin penetration, data presented here suggests a novel role for the protease in egress from the intermediate snail host. This study demonstrates how enzyme activity-based analysis complements genomic and proteomic studies, and is key in elucidating proteolytic function.

SUBMITTER: Ingram JR

PROVIDER: S-EPMC3317910 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Investigation of the proteolytic functions of an expanded cercarial elastase gene family in Schistosoma mansoni.

Ingram Jessica R JR Rafi Salma B SB Eroy-Reveles A Alegra AA Ray Manisha M Lambeth Laura L Hsieh Ivy I Ruelas Debbie D Lim K C KC Sakanari Judy J Craik Charles S CS Jacobson Matthew P MP McKerrow James H JH

PLoS neglected tropical diseases 20120403 4

<h4>Background</h4>Cercarial elastase is the major invasive larval protease in Schistosoma mansoni, a parasitic blood fluke, and is essential for host skin invasion. Genome sequence analysis reveals a greatly expanded family of cercarial elastase gene isoforms in Schistosoma mansoni. This expansion appears to be unique to S. mansoni, and it is unknown whether gene duplication has led to divergent protease function.<h4>Methods</h4>Profiling of transcript and protein expression patterns reveals th ...[more]

PMID: 22509414

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Project description:Parasites with complex life cycles can be susceptible to temperature shifts associated with seasonal changes, especially as free-living larvae that depend on a fixed energy reserve to survive outside the host. The life cycle of Schistosoma, a trematode genus containing some species that cause human schistosomiasis, has free-living, aquatic miracidial and cercarial larval stages that swim using cilia or a forked tail, respectively. The small size of these swimmers (150-350 µm) dictates that their propulsion is dominated by viscous forces. Given that viscosity inhibits the swimming ability of small organisms and is inversely correlated with temperature, changes in temperature should affect the ability of free-living larval stages to swim and locate a host. By recording miracidial and cercarial movement of Schistosoma mansoni using a high-speed camera and manipulating temperature and viscosity independently, we assessed the role each factor plays in the swimming mechanics of the parasite. We found a positive effect of temperature and a negative effect of viscosity on miracidial and cercarial speed. Reynolds numbers, which describe the ratio of inertial to viscous forces exerted on an aquatic organism, were <1 across treatments. Q10 values were <2 when comparing viscosity treatments at 20 °C and 30 °C, further supporting the influence of viscosity on miracidial and cercarial speed. Given that both larval stages have limited energy reserves and infection takes considerable energy, successful transmission depends on both speed and lifespan. We coupled our speed data with mortality measurements across temperatures and discovered that the theoretical maximum distance travelled increased with temperature and decreased with viscosity for both larval stages. Thus, our results suggest that S. mansoni transmission is high during warm times of the year, partly due to improved swimming performance of the free-living larval stages, and that increases in temperature variation associated with climate change might further increase transmission.

Project description:BackgroundThe genomic region that lies between the telomere and chromosome body, termed the subtelomere, is heterochromatic, repeat-rich, and frequently undergoes rearrangement. Within this region, large-scale structural changes enable gene diversification, and, as such, large multicopy gene families are often found at the subtelomere. In some parasites, genes associated with proliferation, invasion, and survival are often found in these regions, where they benefit from the subtelomere's highly plastic, rapidly changing nature. The increasing availability of complete (or near complete) parasite genomes provides an opportunity to investigate these typically poorly defined and overlooked genomic regions and potentially reveal relevant gene families necessary for the parasite's lifestyle.ResultsUsing the latest chromosome-scale genome assembly and hallmark repeat richness observed at chromosome termini, we have identified and characterised the subtelomeres of Schistosoma mansoni, a metazoan parasitic flatworm that infects over 250 million people worldwide. Approximately 12% of the S. mansoni genome is classified as subtelomeric, and, in line with other organisms, we find these regions to be gene-poor but rich in transposable elements. We find that S. mansoni subtelomeres have undergone extensive interchromosomal recombination and that these sites disproportionately contribute to the 2.3% of the genome derived from segmental duplications. This recombination has led to the expansion of subtelomeric gene clusters containing 103 genes, including the immunomodulatory annexins and other gene families with unknown roles. The largest of these is a 49-copy plexin domain-containing protein cluster, exclusively expressed in the tegument-the tissue located at the host-parasite physical interface-of intramolluscan life stages.ConclusionsWe propose that subtelomeric regions act as a genomic playground for trial-and-error of gene duplication and subsequent divergence. Owing to the importance of subtelomeric genes in other parasites, gene families implicated in this subtelomeric expansion within S. mansoni warrant further characterisation for a potential role in parasitism.

Dataset Information

Investigation of the proteolytic functions of an expanded cercarial elastase gene family in Schistosoma mansoni.

Publications

Investigation of the proteolytic functions of an expanded cercarial elastase gene family in Schistosoma mansoni.

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