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Jun 20, 2013

HIV-Derived Antibacterial Compounds Could Help Fight Multidrug-Resistant Pathogens

  • Antibacterial compounds derived from the outer coating of HIV could be the newest weapon in the fight against drug-resistant bacteria, according to research out of the University of Pittsburgh.

    In a new Antimicrobial Agents and Chemotherapy report, Pittsburgh’s Ronald Montelaro, Ph.D., and his colleagues show that these agents, engineered cationic antimicrobial peptides (eCAPs), may not only be useful for the treatment of drug-resistant bacterial infections, but are also easy to manufacture.

    The team began investigating eCAPs as a result of basic research on HIV envelope protein structure and function. Through this work, “we identified highly conserved unique protein sequences that were predicted by computer modeling to assume structures characteristic of natural antibacterial peptides,” Dr. Montelaro said. “Since antibacterial peptides specifically target and disrupt the integrity and function of bacterial membranes, we thought that these similar peptide sequences in the HIV envelope protein might contribute to toxicity and death in infected cells by altering cell membranes.”

    From there, the group began to modify the original HIV peptides, making them smaller and more effective. By altering their amino acid content, peptide length, charge, and hydrophobicity, the team developed a lead eCAP that contains just 12 amino acid residues.

    Dr. Montelaro added that another potential application for his team’s engineered peptides could be biodefense. “eCAPs may be used as a rapid postexposure aerosol treatment in individuals after exposure to aerosolized pathogens, where the goal of immediate treatment would be to rapidly reduce bacterial dose from a lethal to a nonlethal or subclinical level,” he said.

    “Rational design of engineered cationic antimicrobial peptides consisting exclusively of arginine and tryptophan, and their activity against multidrug-resistant pathogens” appears in Antimicrobial Agents and Chemotherapy’s June issue.

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