Mycobacterium smegmatis moxifloxacin persister cells produce high levels of hydroxyl radical, generating genetic resisters selectable not only with moxifloxacin, but also with ethambutol and isoniazid.

Mycobacterium smegmatis moxifloxacin persister cells produce high levels of hydroxyl radical, generating genetic resisters selectable not only with moxifloxacin, but also with ethambutol and isoniazid. Microbiology. 2019 Nov 20;: Authors: Swaminath S, Paul A, Pradhan A, Sebastian J, Nair RR, Ajitkumar P Abstract Bacterial antibiotic persister cells tolerate lethal concentrations of antibiotics but emerge as the antibiotic-sensitive population upon antibiotics withdrawal. However, the possibility of antibiotic-resistant genetic mutants emerging from the antibiotic persister population in the continued exposure to microbicidal concentrations of antibiotics needed investigation. We explored this possibility using the fast-growing Mycobacterium smegmatis as a model organism for Mycobacterium tuberculosis biology, as it is known to incur antibiotic-resistant mutations identical to and at identical target positions as found in the clinical isolates of M. tuberculosis. Here we report that the moxifloxacin (MXF) persister population generate significantly elevated levels of hydroxyl radical. Hydroxyl radical being a sequence-non-specific mutagen, resulted in the emergence of moxifloxacin-resistant genetic mutants at 8-log10 higher frequency from the persister population. Luria-Delbruck experiment (in modified format) confirmed that MXF-resistant mutants emerged de novo from the persister population and were not pre-existent. The nature of th...
Source: Microbiology - Category: Microbiology Authors: Tags: Microbiology Source Type: research