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Modified soil antibiotic may help preserve penicillin effectiveness

Modified tunicamycin poses little to no threat to human or animal cells but is still effective against pathogens.

A common soil bacterium may hold the key to preserving the germ-killing power of penicillin, according to the U.S. Department of Agriculture's Agricultural Research Service (ARS).

USDA scientists in Peoria, Ill., helped mass produce the antibiotic during World War II to treat Allied soldiers and, later, civilians. However, decades of widespread use has since enabled some germs to develop resistance to penicillin.

One strategy to counter this resistance being investigated by an ARS-led team of scientists comes from soil-dwelling members of the bacterial group Streptomyces. These bacteria secrete a compound called "tunicamycin" to keep rival bacteria from reaching choice resources, like rotting plant material.

This includes fending off pathogens like the Staphylococcus aureus, which causes infection in people and animals.

Tunicamycin works by forming holes in the cell walls of encroaching bacteria, causing them to burst open and die, ARS said.

Researchers have known of tunicamycin for decades and initially were excited by its medical and veterinary prospects, especially as a way to overcome the resistance of some pathogens to penicillin-based drugs like oxacillin and methicillin. However, the problem was that tunicamycin also blocked a key protein in human and animal cells, undercutting its potential use.

Now, tunicamycin could get a new lease on life, because ARS scientists have devised a method to retool the compound so that it poses little to no danger to human or animal cells but can still kills pathogenic bacteria.

In laboratory trials, mixing the modified tunicamycin with oxacillin and other penicillin-based drugs made them 32 to 64 times more potent, according to ARS chemist Neil Price and colleagues at the agency's National Center for Agricultural Utilization Research (NCAUR) in Peoria, as well as at the University of Illinois College of Medicine and the Chinese Academy of Sciences.

Additionally, the modified tunicamycin didn't harm cultures of human and hamster cells when it was added to them in tests for toxicity, the team reported in a recent issue of the Journal of Antibiotics.

Price noted that they used tunicamycin-producing Streptomyces bacteria taken from the same repository where the first mass-produced strain of the Penicillium mold is still kept. This repository is the ARS Microbial Culture Collection at NCAUR — designated in 2001 as an International Historic Chemical Landmark for its penicillin contributions.

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