In pursuit of new antibiotics

A new drug with a novel mode of action rescued nematodes from infection with methicillin resistant Staphylococcus aureus (MRSA), paving the way for its development as a potential treatment for antibiotic-resistant bacterial infections.

Antibiotic resistance is a growing problem in human health.

The overuse and misuse of antibiotics has contributed to the emergence of multidrug resistance in bacteria. Coupled with a decline in new antibiotic discovery, this makes ‘superbugs’ such as MRSA and Mycobacterium tuberculosis increasingly difficult to treat.

In this collaborative study, Australian and American researchers designed a new class of antibiotics to target the bacteria-specific membrane protein MscL.

MscL is a mechanosensitive ion channel or gate that changes shape to allow salts and other solutes in and out of a cell, protecting bacteria against lysis.

MscL is an ideal target for drug discovery because it is found in nearly all microbes, it is highly conserved and it is a channel that can act as a point of entry for drugs.

The researchers designed a novel class of ligands that bind to the MscL protein. One antimicrobial of this class, compound 10, was effective against MRSA and showed no cytotoxicity in human cell lines at the therapeutic concentrations.

The researchers also demonstrated that compound 10 cured MRSA infection in the nematode Caenorhabditis elegans. Compound 10 had low levels of toxicity and was also a potent antioxidant, potentially providing an additional benefit by reducing bacterial-induced inflammation.

The researchers concluded that compound 10, and other drugs that target MscL, are potentially important therapeutics that should help prevent the development of antibiotic resistance.

The study was published in The Journal of Antibiotics