Shapiro redux: bacterial resistance (Introduction)

by David Turell , Wednesday, January 10, 2024, 20:37 (107 days ago) @ David Turell

Persister study:

https://phys.org/news/2024-01-notorious-cell-subpopulation-key-antibiotic.html

"Antibiotic overuse can lead to antibiotic resistance, but classic antibiotic resistance might not completely explain why antibiotics sometimes fail. Sub-populations of bacteria called persister cells can survive in the presence of lethal doses of antibiotics for prolonged periods. Although persister cells have been intensively researched, evidence linking them to poor patient outcomes has been limited.

"Scientists led by UNC School of Medicine microbiologist Brian Conlon, Ph.D., and Duke School of Medicine infectious diseases fellow Josh Parsons, MD, Ph.D., have now shown that E. coli can evolve in patients to produce increased persister cells and this leads to increased survival to antibiotics.

***

"Using clinical E. coli bacteremia isolates—bacteria from the blood of patients—Conlon, first author Joshua Parsons, MD, Ph.D., an infectious diseases fellow at Duke University, and colleagues found that high-persister mutants evolved in patients. The researchers then documented a 100-fold increase in persisters in one such mutant when challenged with the exact antibiotic doctors had used to treat patients from which the E. coli had been isolated.

"The mutant bacteria showed no loss of fitness in a mouse infection model and displayed a 10-fold increase in survival following the antibiotic challenge.

"Importantly, Conlon said his team documented the infections and treatment protocols of patients who had been prescribed antibiotics to clear E. coli infections. Conlon said that classical antibiotic resistance was not responsible for the poor outcomes in patients who did not clear infection with antibiotics.

"'Because of this research, we think persister formation is likely a significant contributor to antibiotic treatment failure in patients," Conlon said. "Our research strongly suggests that persister formation is an important metric to consider when treating patients with antibiotics."

"He also said that researchers should develop techniques to identify mutants that are likely to respond poorly to antibiotics because such information would influence treatment choices or duration of treatment. Additionally, developing new therapeutic approaches to target and kill persisters may improve patient treatment outcomes."

Comment: Shapiro showed how bacteria can edit DNA for survival. This is a prime example.

From the article: https://www.pnas.org/doi/10.1073/pnas.2314514121

*In the relapsed E. coli strain with the greatest increase in persisters (100-fold relative to initial isolate), we determined that the increase was due to a loss-of-function mutation in the ptsI gene encoding Enzyme I of the phosphoenolpyruvate phosphotransferase system. The ptsI mutant was equally virulent in a murine bacteremia infection model but exhibited 10-fold increased survival to antibiotic treatment. This work addresses the controversy regarding the clinical relevance of persister formation by providing compelling data that not only do high-persister mutations arise during bloodstream infection in humans but also that these mutants display increased survival to antibiotic challenge in vivo." (my bold)

Comment: this fits Behe's thesis that most evolution of this type involves loss of function. To me this means evolution of major new species is over.