DEFA5
Description
The DEFA5 (defensin alpha 5) is a protein-coding gene located on chromosome 8.
DEFA5 (Defensin, alpha 5), also known as human alpha defensin 5 (HD5), is a protein encoded by the DEFA5 gene. It is expressed in the Paneth cells of the ileum. Defensins are a family of microbicidal and cytotoxic peptides (antimicrobial peptides; AMP) involved in host defense and maintaining intestinal microbiota homeostasis. DEFA5 is the primary AMP that controls the enteric microbiota composition by selectively killing bacterial pathogens while preserving commensals. Defensins are small cationic peptides linked via three intra-molecular disulfide bridges, containing six intra-molecular cysteine residues which form an unalterable and specific pattern of disulfide bridges. This protects them from proteolysis and maintains function in the intestinal lumen. Members of the defensin family are highly similar in protein sequence and distinguished by a conserved cysteine motif. Several human alpha defensin genes appear to be clustered on chromosome 8. In addition to antimicrobial activity, DEFA5 can inactivate and neutralize several bacterial toxins, particularly demonstrating inhibitory potency against Clostridioides difficile toxins. DEFA5 inhibits all three C. difficile toxins A (TcdA), B (TcdB), and CDT in a concentration-dependent manner, with a different inhibitory mechanism for each.
DEFA5, also known as human alpha defensin 5 (HD5), is involved in maintaining sterility in the urogenital system. It has antimicrobial activity against a broad range of bacteria, including Gram-negative Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhimurium, as well as Gram-positive Enterobacter aerogenes, Staphylococcus aureus, Bacillus cereus, Enterococcus faecium, and Listeria monocytogenes. DEFA5 also confers resistance to intestinal infection by Salmonella typhimurium and exhibits antimicrobial activity against enteric commensal bacteria such as Bifidobacterium adolescentis, Lactobacillus acidophilus, Bifidobacterium breve, Lactobacillus fermentum, Bifidobacterium longum, and Streptococcus thermophilus. DEFA5 binds to bacterial membranes, causing membrane disintegration, and induces the secretion of the chemokine IL-8 by intestinal epithelial cells. It also binds to Bacillus anthracis lef/lethal factor, a major virulence factor from Bacillus anthracis, and neutralizes its enzymatic activity.
DEFA5 is also known as DEF5, HD-5.
