Mar. 13, 2002 SAN DIEGO -- A small piece of protein from one end of a larger molecule found in human saliva has been shown in laboratory tests to have potent antimicrobial activity against several types of bacteria and fungi, some of which are resistant to current drugs.
If these findings hold up in animal and human trials, the peptide, labeled MUC7 20-mer, could form the basis for promising new drugs for treating a wide range of infections, said Libuse Bobek, Ph.D., associate professor of oral biology in the University at Buffalo School of Dental Medicine and senior scientist on the research.
Results of the research were presented here today (March 8) at the International Association of Dental Research meeting.
"There is an increasing need for new antimicrobial agents, especially antifungals," said Bobek, "because there are only a handful of these drugs, they are used widely, and several fungal strains already have developed resistance. This is a particular problem for immuno-compromised patients, such as those with HIV/AIDS, organ transplant patients and chemotherapy patients."
This novel peptide, on which Bobek holds a provisional patent, has been shown in vitro to kill the fungal agents that cause the most common opportunistic infections that threaten these patients -- candidiasis, cryptococcosis and aspergillosis -- as well as several bacteria, including E. coli and P. gingivalis, which cause serious intestinal and oral infections, respectively, and S. mutans, which causes dental caries. Moreover, the peptide is active (in vitro) at very low concentrations -- 10 micrograms per milliliter -- shows little or no toxicity to mammalian cells and low tendency to elicit resistance, Bobek said.
"MUC-7 20-mer appears to be a very versatile agent, active at very low dosing, which works comparable to or better than current drugs," she said. "It has a different mechanism of action, but we don't know yet specifically what the mechanism is."
The researchers know that the peptide causes changes in fungal cell-membrane potential; is internalized into the cells, and most likely acts on a specific part of the sub-cellular machinery.
With such potent antimicrobial potential in human saliva, why do people have oral infections? Because the protein segment, the peptide, rarely is present by itself and the large protein molecule from which it is derived doesn't have microbicidal activity, Bobek noted.
The peptide Bobek and colleagues are working with currently is composed of 20 amino acids, but they have found that smaller forms of the peptide still are active in vitro and are experimenting with increasingly shorter pieces.
"We think this naturally-occurring agent has high therapeutic potential for treating microbial infections in general and drug-resistant fungal strains in particular," Bobek said. "It also has potential as a component of artificial saliva for treating salivary dysfunctions that result in increased plaque formation, cavities, gum disease and fungal infections."
Additional researchers on the study are Hongsa Situ, D.D.S.; Christina J. Smith, and Brian M. Kritzman, all of the Department of Oral Biology in the UB School of Dental Medicine.
The research was supported by grants from the National Institute of Dental and Craniofacial Research.
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