Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 57, Issue 4, Pages 1823-1831Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.02237-12
Keywords
-
Categories
Funding
- USDA [2008-35204-04544]
- Oklahoma Center for the Advancement of Science and Technology [AR07.2-087, HR07-113, HR12-051]
- Oklahoma Agricultural Experiment Station [H-2811]
- NIH [DK044632, AI059346]
Ask authors/readers for more resources
Cationic antimicrobial peptides are essential components of the innate immune system. As a major family of mammalian antimicrobial peptides, defensins are expressed mainly by mucosal epithelial cells and promyelocytes. Despite the capacity to kill a broad spectrum of bacteria through physical disruption of membranes, most defensins show substantially reduced antibacterial activities in the presence of monovalent and divalent cations, thereby limiting their therapeutic potential, particularly for the treatment of systemic infections. Genome-wide computational screening of the rat genome led to the identification of the gene for a novel alpha-defensin-related peptide that we termed rattusin. Rattusin shares a highly conserved signal and prosequence with mammalian alpha-defensins, but instead of the canonical alpha-defensin six-cysteine motif, rattusin consists of five cysteines with a distinctive spacing pattern. Furthermore, rattusin is preferentially expressed in Paneth cells of the distal small intestine with potent antibacterial activity against a broad range of Gram-negative and Gram-positive bacteria, including antibiotic-resistant strains. The MICs were mostly in the range of 2 to 4 mu M, with no appreciable toxicity to mammalian cells at up to 100 mu M. In contrast to classical alpha- and beta-defensins, rattusin retained its activity in the presence of physiological concentrations of NaCl and Mg2+, making it an attractive antimicrobial candidate for both topical and systemic applications.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available