As antimicrobial resistance grows, understanding mechanisms of action could help doctors treat patients
Researchers are investigating how disease-causing fungi become resistant to antifungal drugs to explore the potential for the growth of resistance in which harmful microbes develop against drugs. help prevent catastrophic consequences.
“Antimicrobials are fundamental to how we live healthy lives,” says Daniel Charlebois, assistant professor in the physics department and adjunct professor in the biological sciences department, and co-author of the recent paper. study.
Once the organisms that infect the human body develop a permanent resistance to a drug, the drug becomes ineffective or less effective in fighting the infection it was designed to target. increase.
Cells develop resistance to antibiotics in two ways: genetically or non-genetically, explains Charlebois. Genetic resistance is permanent and passed on to offspring. Only in the last decade or so have researchers started digging into non-genetic resistance. The missing piece of the puzzle is what happens when cells transition between these two resistant states. Charlevoix hopes to find out in his research.
Understanding the transition between the two types of resistance is important for finding ways to prevent cells from mutating and evolving to develop genetic resistance.
“People tend to be experts in one form or another of resistance, and it’s only recently that we’ve really started looking into this interaction,” says Charlevoix.
“Trying to understand how these non-genetic mechanisms affect evolution is of great interest to the evolutionary process of drug resistance.”
Charlebois’ work showed that when there are both genetically resistant and non-resistant cells, it takes time for cells to become fully genetically resistant.
“It will take even longer for these genetically resistant mutants to spread to more than 95% of the population,” says Charlevoix.
If cells mutate and become genetically resistant, they remain. However, genetically non-resistant cells can become “susceptible cells”. That is, they either die or stop growing in the presence of the drug. Once the resistance is removed, the infection can be treated.
To examine different subpopulations of resistant cells, Charlebois and Joshua Guthrie, an MSc student in physics, created a population model. “We take population dynamics into account, but previously he was considered a single population. [of resistant cells]’ explains Charlevoix.
Guthrie developed the code and did the simulation work to streamline the process and narrow down the number of experiments that needed to be done in the lab. The modeling part of his study provided important information such as when the first mutations occur in cells.
“It could tell you when you need to add or change medications during treatment,” says Charlebois.
Increased knowledge of the interactions between different resistance mechanisms will provide physicians with important information about the types of drugs to administer and the most effective treatment schedules.
For example, alternating drugs during therapy to take advantage of trade-offs between susceptible, genetically non-resistant, and resistant It may help keep the crowds at bay longer. This could lead to treatment options such as sequential and combination therapy, Charlebois said.
“We’re dealing with a population of interacting entities, different kinds of potential drug resistance,” Charlebois says. “Thinking about how to take advantage of it is not something that is usually considered when developing therapies.”
| | Adriana McPherson
Adrianna MacPherson is a reporter at the University of Alberta. Folio online magazine. The University of Alberta is Troy Media’s editorial content his provider partner.
of opinion expressed by us columnist and contributor They are their own and do not inherently or expressly reflect the views of our publications.
© troy media
Troy Media is an editorial content provider to media outlets and independently hosted community news outlets across Canada.