HIV-derived antibacterial shows promise against drug-resistant bacteria
19-Jun-2013 - A team of researchers at the University of Pittsburgh has developed antibacterial compounds,
derived from the outer coating of HIV, that could be potential treatments for drug-resistant bacterial infections and appear to avoid
generating resistance. These new agents are quite small, making them inexpensive and easy to manufacture. The research was published
in the June 2013 issue of the journal Antimicrobial Agents and Chemotherapy.
The first of many probable applications will likely be the chronic bacterial infections in the lungs of cystic fibrosis
patients "that frequently develop resistance to all standard antibiotics, and are the leading cause of death in these patients," says
senior author Ronald Montelaro.
The lead compound shows powerful antibacterial activity against clinical isolates of diverse pathogenic bacteria that
are resistant to most antibiotics. These agents, called engineered cationic antimicrobial peptides (eCAPs) "may be applicable to
treatment of other respiratory infections, topical infections, and systemic infections," says Montelaro.
The genesis of the new agent was basic research on HIV envelope protein structure and function, says Montelaro. As part
of this research, "we identified highly conserved unique protein sequences that were predicted by computer modeling to assume
structures characteristic of natural antibacterial peptides. 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."
The team engineered the original HIV peptides for greater effectiveness and smaller size, the latter to reduce manufacturing
expenses. The engineering involved modifying amino acid content (they contain just two different amino acids), peptide length, charge,
and hydrophobicity. The current paper describes the third generation peptides. The lead agent contains just 12 amino acid residues.
"Another potential application is biodefense, where 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," says Montelaro.
Antimicrobial Agents and Chemotherapy is a publication of the American Society for Microbiology (ASM). The ASM is the largest
single life science society, composed of over 39,000 scientists and health professionals. Its mission is to advance the microbiological
sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and
environmental and economic well-being worldwide.
American Society for Microbiology
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