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Metallopolymers Protect Penicillin-Like Antibiotics from Bacterial Beta-Lactamase

By BiotechDaily International staff writers
Posted on 12 May 2014
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Image: MRSA (in yellow) is vulnerable to a new polymer-antibiotic combination (Photo courtesy of the [US] National Institute of Allergy and Infectious Diseases).
Image: MRSA (in yellow) is vulnerable to a new polymer-antibiotic combination (Photo courtesy of the [US] National Institute of Allergy and Infectious Diseases).
Novel drug combinations that unite classical penicillin-like antibiotics with metallopolymers effectively kill bacteria, including "superbugs" such as MRSA (methicillin-resistant Staphylococcus aureus) that had developed beta-lactamase enzyme-based resistance to the antibiotics.

Metallopolymers are a class of polymers with metal atoms either in the backbone or at the side chain. These polymers exhibit many unprecedented properties and functions that conventional organic polymers usually lack. Among metallopolymers, metallocene-containing polymers have attracted significant attention due to their unique electrochemical, catalytic, and optical properties. Metallocene-containing polymers are widely used for redox active systems as recognition of ions and sugars and modification of electrodes.

MRSA, a complex of multi-drug-resistant Gram-positive bacterial strains, has proven especially problematic in both hospital and community settings by deactivating conventional beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems, through various mechanisms, resulting in increased mortality rates and hospitalization costs.

To correct this problem, investigators at the University of South Carolina (Columbia, USA) developed an improved class of beta-lactam antibiotics by conjugating classical penicillin-like antibiotics to cobaltocenium metallopolymers.

They reported in the March 17, 2014, online edition of the Journal of the American Chemical Society that these combinations exhibited a synergistic effect against MRSA by efficiently inhibiting activity of beta-lactamase and effectively lysing bacterial cells. Various conventional beta-lactam antibiotics, including penicillin-G, amoxicillin, ampicillin, and cefazolin, were protected from beta-lactamase hydrolysis via the formation of unique ion-pairs between their carboxylate anions and cationic cobaltocenium moieties.

"Instead of developing new antibiotics, here we ask the question, "Can we recycle the old antibiotics"? With traditional antibiotics like penicillin G, amoxicillin, ampicillin, and so on, can we give them new life"? In the United States every year, around 100,000 patients die of bacteria-induced infections," said senior author Dr. Chuanbing Tang, professor of chemistry and biochemistry at the University of South Carolina. "And the problem is increasing because bacteria are building resistance. It is a really, really big problem, not only for individual patients, but also for society."

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University of South Carolina



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