The threat of antibiotic-resistant bacterial infections has been growing across human civilization for years, but a new look at a plant pathogen discovered years ago reveals a potential new method of combating it—an antibacterial agent that works like nothing else deployed in medicine.
Called albicidin, it belongs to a pathogen that causes a disease in sugarcane called leaf scald, but also seems to attack bacteria in a completely different way than common antibiotics like fluoroquinolones.
A new study looking at the mechanism used by albicidin to attack lifeforms found that it works as a DNA topoisomerase inhibitor.
Topoisomerases are nuclear enzymes that play essential roles in DNA replication, transcription, chromosome segregation, and recombination. In the study, albicidin was found to efficiently lock DNA gyrase in antibiotic-resistant E. coli, caused double-strand DNA breaks, and eventual cell death.
“We could not elicit any resistance towards albicidin in the laboratory,” said Dmitry Ghilarov, one of the researchers in a British-German-Polish group that studied the potential antibiotic at the John Innes Center in Norwich, UK.
“That is why we are really excited—because we think it will be very hard for bacteria to evolve resistance against albicidin-derived antibiotics.”
Antibiotic-resistant bacterial infections are one of the biggest challenges in conventional medicine today. Far more dangerous in terms of case fatality and total fatality than COVID-19 has ever been, developing new methods of fighting these infections has nevertheless been a task largely ignored by major pharma companies.
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“Now we have a structural understanding, we can create modifications of albicidin to improve its efficacy and pharmacological properties,” said Ghilarov.
“We believe this is one of the most exciting new antibiotic candidates in many years. It has extremely high effectiveness in small concentrations and is highly potent against pathogenic bacteria—even those resistant to the widely used antibiotics such as fluoroquinolones.”
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Animal infection models have already established both safety and efficacy in two derivatives of ablicidin.
Furthermore, the researchers write in their study that inhibitors of DNA gyrase represent an untapped reservoir of potential antibiotic compounds, and building a broad understanding of one will help expand the field outward, potentially turning over new leaves in the development of a whole new class of pharmaceuticals.
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