With many disease-causing bacteria ratcheting up their shields against current drugs, new tactics are vital to protect people from treatment-resistant infections.
Lowering mutation rates in harmful bacteria might be an as yet untried way to hinder the emergence of antimicrobial-resistant pathogens. This proposed strategy comes from recent findings in infectious disease research at UW Medicine in Seattle.
The report on this work is published this week in Molecular Cell, one of the journals of Cell Press. The lead author is Mark N. Ragheb, an M.D./Ph.D. student at the University of Washington School of Medicine. The senior researcher is Houra Merrikh, associate professor of microbiology at the UW medical school.
While most efforts against antimicrobial resistance concentrate on producing better antibiotics, the scientists note, “History shows that resistance arises regardless of the nature or potency of new drugs.”
Deaths from antibiotic-resistant infections, they explain, have reached alarming numbers worldwide, and show signs of surpassing mortality from other causes by mid-century.
In looking for another approach to combating this public health threat, the team of microbiologists, genome scientists, pathobiologists and molecular and cellular biologists found evidence for a key promoter of mutations in many different bacteria. This protein factor, DNA translocase Mfd, seems to speed resistance in diverse species toward every antibiotic that was tested.
The researchers call bacterial proteins like Mfd “evolvability factors” because, by increasing mutation rates, they propel the evolution of bacteria. Unlike many multicellular organisms, bacteria evolve quickly. This allows their species to survive or escape suddenly changing conditions, scarcity of nutrients and hostile environments — including attempts to destroy them with antibiotics or immune responses.
Many types of bacteria produce Mfd, an indication of its important physiological role in cells. While it was once thought to assist in DNA repair, cells missing it are not more sensitive to DNA damaging agents. Those with too much of it are actually more prone to DNA damage.
Source and further reading: UW School of Medicine