Friday, 28 July 2017

New approach to battle drug-resistant bacteria

Researchers at University of Utah Health have developed a rapid screening method to identify beneficial pairs of existing FDA-approved drugs to combat multi-drug resistant (MDR) bacterial infections. The microbiologists analyzed a bacterial dataset consisting of 4,000 E. coli mutants grown in the presence of 100 FDA-approved drugs. Each mutant is missing a specific gene and interacts with each drug in a specific way, producing a unique chemical genetic signature.

The approach identified 14 drugs that could be paired synergistically. The most promising synergistic pairing in this study combined azidothymidine (AZT), one of the earliest drugs prescribed to treat HIV-AIDS, with floxuridine, a cancer drug with a similar chemical genetic signature as a commonly prescribed antibiotic ¾ trimethoprim.

AZT blocks DNA replication, while floxuridine, like the antibiotic trimethoprim, prevent bacteria from repairing their DNA. While many bacteria have developed resistance to trimethoprim, floxuridine remains effective, even against trimethoprim-resistant bacteria, because it works by another mechanism.

Several of the drugs identified in this study are not currently used as antibiotics, but produce an effective response against MDR bacteria. The synergistic drug pairing also has the potential to slow the evolution of resistance to the drug therapies.


Morgan A. Wambaugh, Viplendra P. S. Shakya, Adam J. Lewis, Matthew A. Mulvey, Jessica C. S. Brown. High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance. PLOS Biology, 2017; 15 (6): e2001644 DOI: 10.1371/journal.pbio.2001644

Posted by Dr. Tim Sandle