Screening existing drugs to uncover new weapons against antibiotic-resistant bacteria

The researchers analyzed some 10,000 compounds, finding three approved drugs that might prove effective at combating CRE(Credit: oliver.dodd/C.C. 2.0)

Bacteria that are resistant to standard antibiotics represent one of the biggest threats to global health today, and one particular type, known as carbapenem-resistant Enterobacteriaceae (CRE), was recently classified by the US Centers for Disease Control and Prevention as having the most urgent antimicrobial resistance threat level possible. Help might just be at hand though, with researchers from the Beth Israel Deaconess Medical Center (BIDMC) using a screening method to identify existing drugs that might well prove effective against the dangerous bacteria.

Across the globe, scientists are working around the clock to find means of tackling antibiotic-resistant bacteria. From quantum-dots to natural clay, we're trying just about anything to combat the threat, but the reality is that the rate at which we're producing new antibiotics is steadily decreasing, and we're extremely short on ways of fighting resistant bacteria like CRE.

This got the BIDMC researchers thinking – what if potential treatments might be hiding in plain sight, in existing drugs?

The team worked to examine some 10,000 bioactive molecules – compounds with known activity – that are already FDA-approved, as well as veterinary drugs and certain inhibitors not currently used for treatment. They used process known as high-throughput screening to study the compounds, searching for candidates that might be able to tackle CRE.

From the thousands of drugs, 79 compounds were identified that inhibit CRE, of which three are approved for human and animal use. The identified compounds are a therapy designed to combat HIV, known as azidothymidine or AZT, a vetinary medicine called apramycin and gonorrhoea treatment known as spectinomycin.

The drugs could prove effective treatments in their current form, but may also serve as a solid starting point for the development of new antiobiotics.

"These antimicrobials currently have other intended uses and are not currently considered as treatments for CRE, however our findings suggest they could potentially be repurposed for CRE treatment," said study member Kenneth Smith, PhD. "Specifically, these antibiotics could be structurally modified to further increase their activity and prevent resistance from developing against them."

Looking forward, the drugs will be tested against an animal model of CRE infection. The researchers also plan to continue their search for other compounds that might prove effective against antibiotic-resistant bacteria, and plan to perform the same analysis on a collection of more than 200,000 novel drug compounds, the biological activity of which is yet to be characterized.

Full details of the work are available in the journal ASSAY and Drug Development Technologies.

Source: BIDMC

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