Journal Article

SP-1, a Serine Protease from the Gut Microbiota, Influences Colitis and Drives Intestinal Dysbiosis in Mice

Mkaouar, Héla, Gargouri, Ali, Soussou, Souha, Jablaoui, Amin, Lesner, Adam, Gruba, Natalia, Maguin, Emmanuelle, Rhimi, Soufien, Mariaule, Vincent, Rhimi, Moez, Kriaa, Aicha

2021

Overview

Increased protease activity has been linked to the pathogenesis of IBD. While most studies have been focusing on host proteases in gut inflammation, it remains unclear how to address the potential contribution of their bacterial counterparts. In the present study, we report a functional characterization of a newly identified serine protease, SP-1, from the human gut microbiota. The serine protease repertoire of gut Clostridium was first explored, and the specificity of SP-1 was analyzed using a combinatorial chemistry method. Combining in vitro analyses and a mouse model of colitis, we show that oral administration of recombinant bacteria secreting SP-1 (i) compromises the epithelial barrier, (ii) alters the microbial community, and (ii) exacerbates colitis. These findings suggest that gut microbial protease activity may constitute a valuable contributor to IBD and could, therefore, represent a promising target for the treatment of the disease.

• Publisher: MDPI AG,MDPI
• Subject: Amino Acid Sequence / Amino acids / Animals / Bacteria / Binding sites / Cloning / Colitis / Colitis - chemically induced / Colitis - enzymology / Colitis - microbiology / Combinatorial chemistry / Conserved Sequence / Dextran Sulfate / Digestive system / Dysbacteriosis / Dysbiosis - enzymology / Dysbiosis - microbiology / E coli / Feces - enzymology / Gastrointestinal Microbiome / Gastrointestinal tract / Gene expression / gut microbiota / holobiont / Inflammation / Inflammation - pathology / Inflammatory bowel disease / inflammatory bowel diseases / Intestinal microflora / Intestinal Mucosa - pathology / Intestines - pathology / Kinetics / Lactobacillus - enzymology / Life Sciences / Male / Mice / Mice, Inbred C57BL / microbiome / Microbiota / Oral administration / Peptides / Phylogenetics / Phylogeny / Physiology / Plasmids / Prokaryotes / Proteins / Serine / serine proteases / Serine Proteases - administration & dosage / Serine Proteases - chemistry / Serine Proteases - isolation & purification / Serine Proteases - metabolism / Serine proteinase / Software / Substrate Specificity / Subtilisin - chemistry