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article imageOld antibiotic compounds could become the next life-saving drugs

By Tim Sandle     Feb 20, 2018 in Science
Leeds - The battle between humans and antimicrobial resistant bacteria continues to be one of the major problems affecting society. A new initiative from University of Leeds scientists aims to review previously discarded medicinal products.
The review aims to see if chemicals discarded in the past can be ‘resupposed’ to create new antimicrobial compounds. Such research is necessary due to the continued rise of antimicrobial resistance organisms, with the implication being that bacterial infections that were easily treatable in the past are no longer so.
The causes of antimicrobial resistance are many. These include naturally evolved resistance from bacteria (such as the exchanging of genetic information) to the misprescribing of antibiotics by medics for non-bacterial infections, like viral infections; and the arguable misuse of antibiotics to create leaner meat with farm animals.
Back in the heyday of antibiotic development in the mid-20th century several different chemical compounds were found to have antibacterial properties. However, only a few of these compounds were ever developed into antimicrobial drugs. This has led the microbiologists based at the University of Leeds to go back and re-examine these candidate antimicrobials of yesteryear.
According to Dr Alex O’Neill, who works at the Antimicrobial Research Centre at Leeds University: “We’re showing the value of reviewing compounds previously put on the back of the shelf. Amongst the 3,000 or so antibiotics discovered to date, only a handful have been brought into clinical use. There may be a wealth of compounds out there with untapped potential.”
The researcher explains further: “At the moment, the bugs are outsmarting the scientists, and we can’t allow that to continue. By studying compounds which past research has shown already have antibacterial properties, there is scope for a potential fast-track through the challenging early stages of drug discovery. This approach could pave the way for life-saving new drugs.”
So far the researchers have identified one compound, first proposed in the 1940s, as a contender for a new class of antibiotic medicine. This is a family of chemicals called actinorhodins. From this family, one specific compound (y-ACT) is worthy of further study.
Initial studies have shown that y-ACT is effective against the so-termed ESKAPE group of pathogens (bacteria that can ‘escape’ the action of conventional antimicrobial drugs). Bacteria in this grouping include hospital acquired infectious agents like Staphylococcus aureus and Klebsiella pneumoniae.
A second chemical called pentyl pantothenamide, first assessed in the 1970s, also shows promise for the next stage of research. The research into this has been published in the journal Biochemistry (“The Mechanism of Regulation of Pantothenate Biosynthesis by the PanD–PanZ·AcCoA Complex Reveals an Additional Mode of Action for the Antimetabolite N-Pentyl Pantothenamide (N5-Pan)”).
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