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Serine protease inhibitors and human wellbeing interplay: new insights for old friends.

ABSTRACT: Serine Protease Inhibitors (Serpins) control tightly regulated physiological processes and their dysfunction is associated to various diseases. Thus, increasing interest is given to these proteins as new therapeutic targets. Several studies provided functional and structural data about human serpins. By comparison, only little knowledge regarding bacterial serpins exists. Through the emergence of metagenomic studies, many bacterial serpins were identified from numerous ecological niches including the human gut microbiota. The origin, distribution and function of these proteins remain to be established. In this report, we shed light on the key role of human and bacterial serpins in health and disease. Moreover, we analyze their function, phylogeny and ecological distribution. This review highlights the potential use of bacterial serpins to set out new therapeutic approaches.

SUBMITTER: Mkaouar H

PROVIDER: S-EPMC6718151 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Serine protease inhibitors and human wellbeing interplay: new insights for old friends.

Mkaouar Héla H Akermi Nizar N Kriaa Aicha A Abraham Anne-Laure AL Jablaoui Amin A Soussou Souha S Mokdad-Gargouri Raja R Maguin Emmanuelle E Rhimi Moez M

PeerJ 20190830

Serine Protease Inhibitors (Serpins) control tightly regulated physiological processes and their dysfunction is associated to various diseases. Thus, increasing interest is given to these proteins as new therapeutic targets. Several studies provided functional and structural data about human serpins. By comparison, only little knowledge regarding bacterial serpins exists. Through the emergence of metagenomic studies, many bacterial serpins were identified from numerous ecological niches includin ...[more]

PMID: 31531264

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Project description:BACKGROUND:Subtilisin-like serine proteases play an important role in pathogenic fungi during the penetration and colonization of their hosts. In this study, we perform an evolutionary analysis of the subtilisin-like serine protease genes of subphylum Pezizomycotina to find if there are similar pathogenic mechanisms among the pathogenic fungi with different life styles, which utilize subtilisin-like serine proteases as virulence factors. Within Pezizomycotina, nematode-trapping fungi are unique because they capture soil nematodes using specialized trapping devices. Increasing evidence suggests subtilisin-like serine proteases from nematode-trapping fungi are involved in the penetration and digestion of nematode cuticles. Here we also conduct positive selection analysis on the subtilisin-like serine protease genes from nematode-trapping fungi. RESULTS:Phylogenetic analysis of 189 subtilisin-like serine protease genes from Pezizomycotina suggests five strongly-supported monophyletic clades. The subtilisin-like serine protease genes previously identified or presumed as endocellular proteases were clustered into one clade and diverged the earliest in the phylogeny. In addition, the cuticle-degrading protease genes from entomopathogenic and nematode-parasitic fungi were clustered together, indicating that they might have overlapping pathogenic mechanisms against insects and nematodes. Our experimental bioassays supported this conclusion. Interestingly, although they both function as cuticle-degrading proteases, the subtilisin-like serine protease genes from nematode-trapping fungi and nematode-parasitic fungi were not grouped together in the phylogenetic tree. Our evolutionary analysis revealed evidence for positive selection on the subtilisin-like serine protease genes of the nematode-trapping fungi. CONCLUSIONS:Our study provides new insights into the evolution of subtilisin-like serine protease genes in Pezizomycotina. Pezizomycotina subtilisins most likely evolved from endocellular to extracellular proteases. The entomopathogenic and nematode-parasitic fungi likely share similar properties in parasitism. In addition, our data provided better understanding about the duplications and subsequent functional divergence of subtilisin-like serine protease genes in Pezizomycotina. The evidence of positive selection detected in the subtilisin-like serine protease genes of nematode-trapping fungi in the present study suggests that the subtilisin-like serine proteases may have played important roles during the evolution of pathogenicity of nematode-trapping fungi against nematodes.

Dataset Information

Serine protease inhibitors and human wellbeing interplay: new insights for old friends.

Publications

Serine protease inhibitors and human wellbeing interplay: new insights for old friends.

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