Scientists explore the action mechanism of a new antibiotic.

[2greys]

All bacterial cells contain topoisomerases, an important group of enzymes that help deal with spatial difficulties stemming from bacterial cell division associated with circular DNA replication. Topoisomerases can be of two types, I and II, depending 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 that comprises levofloxacin, ciprofloxacin, and others. Unfortunately, bacteria easily acquire resistance to FQs through mutations in topoisomerase-encoding genes. The emergence 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 capable of blocking 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 impact of the “reverse antibiotic” on gram-negative bacteria and showed for the first time ever that nybomycin can also be effective against unstable topoisomerases.

skoltech.ru/en/2021/03/scie...

[Snackjack]

Hope this one progresses very soon as there are many people like me with inflammatory disease. Thank you 2 greys.

[Badbessie]

As always very interesting.

[Alberta56]

Gosh. This sounds promising.

[Mavary]

It’s a little bit complicated for me but it does explain why I became resistant to Ciprofloxacin.

[MiriamW]

Interesting, but you (i.e. the study authors) have omitted to state the major problem which is that mammalian mitochondrial DNA also has topoisomerase type II (a throwback to the primaeval soup everything crawled out of). Any antibiotic developed to target this enzyme to destroy bacteria (there are, I believe, 3 other classes as well as the fluoroquinolones) also targets OUR mitochondria. For readers who are not sure, our mitochondria produce the charge in our batteries, the powerhouses of our cells, basically we need them to be not damaged.

The fluoroquinolones have a long history of causing severe adverse reactions, which can be persistent and disabling, even life threatening Their damaging effects continue for very many years and include chronic severe pain (nerve damage), joint and muscle damage, gut problems (destroyed microbiome), major organ damage, psychiatric problems - you name it, if its cells contain mitochondria it will sustain some damage. The severity seems to depend on the health of the individual's mitochondria in the first place and the amount of fluoroquinolones (or other ABs) taken.