Study shows the effect of ‘reverse antibiotic’ on gram-negative bacteria

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• Source: Skolkovo Institute of Science and Technology (Skoltech)


• Date: 05 Mar,2021

Researchers from Skoltech and MSU have investigated antibiotic nybomycin that could prove effective against bacteria resistant to other antibiotics. Their research was published in the journal Antimicrobial Agents and Chemotherapy.

All bacterial cells contain topoisomerases, a significant group of enzymes that help deal with spatial problems stemming from bacterial cell division related to circular DNA replication. Topoisomerases can be of two types, I and II, based on breaks they produce in DNA (one strand or double strand).

Type II often acts as a target for antibiotics, including fluoroquinolones (FQ), a common group of antibiotics which comprises levofloxacin, ciprofloxacin, and many others. Unfortunately, bacteria easily acquire resistance to FQs via mutations in topoisomerase-encoding genes. The development of resistant pathogenic strains is a global problem in healthcare, therefore, identifying alternative pathways to thwart their persistence is the current frontier in drug discovery.

Nybomycins reported to be”reverse antibiotics” are effective at blocking fluroquinolone resistant DNA-gyrase (among those type II Topoisomerases). Previously, this effect was observed in gram-positive germs only (germs can be either gram-positive or gram-negative, based on their cell wall structure).

A team headed by Olga Dontsova, a professor at Skoltech and Moscow State University, has demonstrated the impact of the”reverse antibiotic” on gram-negative bacteria and showed for the first time ever that nybomycin can also be effective against shaky topoisomerases.

“Interestingly, the first inhibitors of topoisomerases of type II were discovered among quinolones, artificially synthesized molecules. Now increasingly more organic molecules are found that are effective against the same target. Nybomycin, a natural inhibitor of topoisomerases II, disrupts fluoroquinolone-resistant gyrases, which means it can be used when fluoroquinolones, the classic gyrase inhibitors, don’t work.

This is the first study that looks into the details of inhibition of topoisomerases II in gram-negative bacteria using nybomycin which has been shown to block fluoroquinolone-sensitive and fluoroquinlone-resistant forms of gyrase in Escherichia coli.”

Ilya Osterman, Principal Research Scientist, Skoltech Center for Life Sciences

According to Olga Dontsova:”Finding ways to overcome bacterial resistance to antibiotics is particularly significant in pandemics, when secondary bacterial infections that are difficult to fight often develop”.