ATP burst is the dominant driver of antibiotic lethality in <i>Mycobacterium smegmatis</i>.

ABSTRACT: Antibiotic-tolerant bacteria, due to their unique physiology, are refractory to antimicrobial killing and pose challenges for infection control. Incomplete knowledge of how bactericidal antibiotics work limits our understanding of partial resistance due to phenotypic tolerance in mycobacteria, a driver for developing genetic resistance. Using proteomics, ¹³C isotopomer analysis, genetic and biochemical assays, we investigated the physiological response of M. smegmatis challenged with aminoglycoside and fluoroquinolone antibiotics. Two distinct classes of antibiotics elicited remarkably similar responses and increased flux through the TCA cycle, causing enhanced respiration, ROS generation, and ATP burst. We observed that excessive ATP levels and not ROS dominantly contrib

SUBMITTER: Lodhiya T 

PROVIDER: S-EPMC12799214 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature