Today I read an article describing tolerance and persistence of Escherichia coli, a problematic intestinal and extra-intestinal pathogen, which may be due to decreases in ATP levels. Tolerance and persistence, not to be confused with antibiotic resistance, is an often overlooked phenomena that can have dire consequences for patient treatment in certain situations. Recently, my laboratory at St Jude Children’s Research Hospital published a paper describing Enterococcus persistence and tolerance to antibiotics in a boilm, even when clinical MIC testing showed sensitivity.
The E. coli paper describes a similar persistence and lack of activity of antibiotics, in the absence of true resistance mechanisms. Here, Shan et. al. describes lower levels of ATP as a direct cause of the decreased activity of antibiotics. We usually focus on the activity of RelA and ppGpp in this (stringent response), but by using a relAspoT mutant, they were still able to show decreased sensistivity to antibiotics and stressors.
During decreases cellular respiration and growth, as oftentimes happens when bacteria reside in a biofilm, it is accepted that many antibiotic targets, such as DNA gyrase, RNA polymerase and the ribosome are not always needed, therefore antibiotics would have no effect. This current study extends this idea to indicate that the direct reduction in cellular energy (ATP) leads to the direct decrease in activity of biological pathways in bacteria.
Take a read and enjoy!