PMID:9169780

Citation	Porter, EM, van Dam, E, Valore, EV and Ganz, T (1997) Broad-spectrum antimicrobial activity of human intestinal defensin 5. Infect. Immun. 65:2396-401
Abstract	Defensins are antibiotic peptides expressed in human and animal myeloid and epithelial cells. Due to the limited availability of natural peptides, the properties of human epithelial defensins have not been studied. We assayed the microbicidal activity of recombinant human intestinal defensin 5 (rHD-5) in the presence of salt (O to 150 mM NaCl) with varied pH (pH 5.5 to pH 8.5) and trypsin (25 and 250 microg/ml). rHD-5 exhibits microbicidal activity against Listeria monocytogenes, Escherichia coli, and Candida albicans. In contrast to cryptdins, the mouse intestinal defensins, rHD-5 is active against both mouse-virulent wild-type Salmonella typhimurium and its isogenic, mouse-avirulent phoP mutant. In the presence of salt, rHD-5 activity was reduced, and at 100 mM NaCl, activity against S. typhimurium was abolished. However, at all salt concentrations tested, rHD-5 remained bactericidal to L. monocytogenes. Activity against L. monocytogenes was not pH dependent but was diminished at pH 5.5 against wild-type S. typhimurium. This acid-induced resistance may have been mediated by the virulence gene regulator phoP, since the phoP mutant was equally sensitive at pH 5.5 and pH 7.4. In the presence of trypsin, rHD-5 was partially cleaved, but even then, rHD-5 at 100 microg/ml decreased the number of CFU of wild-type S. typhimurium by more than 99%. The persistence of microbicidal activity of rHD-5 under these conditions supports the notion that naturally occurring human intestinal defensin is an effective arm of mucosal host defense.
Links	PubMed PMC175332
Keywords	Animals; Anti-Infective Agents/pharmacology; Blood Proteins/chemistry; Blood Proteins/pharmacology; Defensins; Dose-Response Relationship, Drug; Drug Stability; Humans; Hydrogen-Ion Concentration; Mice; Recombinant Proteins/pharmacology; Trypsin/pharmacology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:DEF5		GO:0042742: defense response to bacterium	ECO:0000314:		P		The antibacterial activity of human intestinal defensin 5 was determined using an antimicrobial assay. Figure 1 shows the activity of human defensin 5, in the from of purified rHD-5, against the bacteria L. monocytogenes, E. coli ML35p, and S. typhimurium (wild type, closed symbols; phoP mutant, open symbols). In a concentration dependent manner, rHD-5 showed antibacterial activity against all three bacterial strains tested.	complete CACAO 12387
HUMAN:DEF5		GO:0051873: killing by host of symbiont cells	ECO:0000314:		P		Human intestinal defensin 5 has the ability to kill cells of other organisms. The antimicrobial activity of human intestinal defensin 5 was determined using an antimicrobial assay. Figure 1 shows the activity of human defensin 5, in the form of purified rHD-5, against the bacteria L. monocytogenes, E. coli ML35p, and S. typhimurium. In a concentration dependent manner, rHD-5 showed antibacterial activity against all three bacterial strains tested.	complete CACAO 12526
HUMAN:DEF5		GO:0002376: immune system process	ECO:0000314:		P		Human intestinal defensin 5 plays a role in immune system processes. The antimicrobial immune activity of human intestinal defensin 5 was determined using an antimicrobial assay. Figure 1 shows the activity of human defensin 5, in the form of purified rHD-5, against the bacteria L. monocytogenes, E. coli ML35p, and S. typhimurium. In a concentration dependent manner, rHD-5 showed antibacterial activity against all three bacterial strains tested.	complete CACAO 12527
HUMAN:DEF5		GO:0016045: detection of bacterium	ECO:0000314:		P		Human intestinal defensin 5 has the ability to detect bacterial cells and express antimicrobial activity against them. The antimicrobial activity of human intestinal defensin 5 was determined using an antimicrobial assay. Figure 1 shows the activity of human defensin 5, in the form of purified rHD-5, against the bacteria L. monocytogenes, E. coli ML35p, and S. typhimurium. In a concentration dependent manner, rHD-5 showed antibacterial activity against all three bacterial strains tested.	complete CACAO 12528

References

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