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Synthetic corkscrew peptide kills antibiotic-resistant Gram-negative bacteria
Date:1/24/2013

HOUSTON An engineered peptide provides a new prototype for killing an entire category of resistant bacteria by shredding and dissolving their double-layered membranes, which are thought to protect those microbes from antibiotics.

The synthetic peptide was effective in lab experiments against antibiotic-resistant Gram-negative bacteria, which cause a variety of difficult-to-treat, potentially lethal infections such as pneumonia and sepsis.

The team led by scientists at The University of Texas MD Anderson Cancer Center reported its findings online in advance of print this week at the Proceedings of the National Academy of Science.

"The antibiotic pipeline against multidrug-resistant Gram-negative problem pathogens is a major unmet need in contemporary medicine; as such, our new antimicrobial agent holds immediate promise," said co-senior author Wadih Arap, M.D., professor in MD Anderson's Department of Genitourinary Medical Oncology and the David H. Koch Center.

Arap, Renata Pasqualini, Ph.D., also a co-senior author, professor in genitourinary medical oncology and the Koch center, and colleagues have previously constructed peptide combinations that are in development against cancer and white fat cells.

"The prototype introduced here as an antibiotic candidate has a unique mechanism of action and translational applications readily identified," Pasqualini said.

Gram-negative bacteria that are highly resistant to existing treatments include E. coli, Acinetobacter baumanii, Pseudomonas aeruginosa, and kebsiella pneumonia. These infections are often present in health care settings and most threatening to people with weakened immune systems.

The spiral peptide called KLAKLAKKLAKLAK acts against bacteria by puncturing their lipid bilayer membranes and has only low toxicity toward mammalian cells. These antimicrobial peptides, however, are subject to routine destruction by host enzymes
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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