Scientists from Skoltech and MSU have studied an antibiotic nybomycin that may be effective against other antibiotic-resistant bacteria. Their research was published in the journal Antimicrobial agents and chemotherapy.
All bacterial cells contain topoisomerases, an important group of enzymes that help address spatial problems arising from bacterial cell division associated with accurate DNA reproduction. Topoisomerases can be of two types, I and II, depending on the breakdown they make in DNA (single strand or double strand).
Type II often acts as a target for antibiotics, including fluoroquinolones (FQ), a common group of antibiotics that include levofloxacin, ciprofloxacin, and others. Unfortunately, bacteria are readily susceptible to FQs through mutations in topoisomerase encoding genes. The emergence of resistant pathogenic rays is a global problem in healthcare, therefore, the identification of alternative pathways to stop the current stability in drug detection.
Nybomycins reported as “reverse antibiotics” are able to inhibit fluroquinolone-resistant DNA-gyrase (one of the type II Topoisomerases). Previously, this effect was observed in gram-positive bacteria only (bacteria can be either gram-positive or gram-negative, depending on their cell wall structure).
A team led by Olga Dontsova, a professor at Skoltech and Moscow State University, has demonstrated the effects of the “reverse antibiotic” on gram-negative bacteria and has shown for the first time that nybomycin can be effective. against unstable topoisomerases.
“Interestingly, the first protectors of type II topoisomerases were found among quinolones, artificially synthesized molecules. Now more natural molecules are found that are effective against the same target. Nybomycin, a natural inhibitor of topoisomerases II, interferes with fluoroquinolone-resistant gyrases, which means it can be used when fluoroquinolones, the classic gyrase protector, do not work.
This is the first study that looks into details of inhibition of topoisomerases II in gram-negative bacteria using nybomycin that has been proven to inhibit forms of gyrase that are sensitive to fluoroquinolone and fluoroquinlone antagonists in Escherichia coli. “
Ilya Osterman, Principal Research Scientist, Skoltech Center for Life Sciences
According to Olga Dontsova: “Finding ways to overcome antibiotic resistance is especially important in infectious diseases, when difficult-to-fight secondary bacterial diseases often develop. “.
Source:
Skolkovo Institute of Science and Technology (Skoltech)
Magazine Reference:
Shiriaev, DI, et al. (2021) Nybomycin inhibits all types of E. coli DNA gyrase – fluoroquinolone-sensitive and fluoroquinolone resistant. Antimicrobial agents and chemotherapy. doi.org/10.1128/AAC.00777-20.