Fate of in vitro cultured Mycobacterium abscessus populations when exposed to moxifloxacin
Abstract
Given the current need for predictive persisting model for Mycobacterium abscessus, we adopted a classical assay to study drug-tolerant bacterial persisters, focusing on the behavior of a small antibiotic-insensitive subpopulation during prolonged exposure to moxifloxacin. Our study showed a wide-ranging response of M. abscessus, depending on antibiotic concentration, growth stage of mycobacterial cultures, and the availability of potassium ions in the medium. Mid-logarithmic cultures, initially grown in either balanced or K+-free medium, contained small sup-populations capable of prolonged and stable survival in the presence of moxifloxacin. The response of these mid-log cultures to antibiotic exposure involved initial killing, followed by regrowth at 1–2 MBCs of moxifloxacin or a substantial reduction of the antibiotic-insensitive subpopulation to fewer than 102 CFU/mL at 16 MBCs. In stationary-phase cultures grown in a complete medium, a consistent number of viable cells was observed when exposed to a high dose of moxifloxacin. In contrast, antibiotic-insensitive subpopulations in stationary-phase M. abscessus cultures under potassium-deficient conditions experienced gradual killing across a wide range of moxifloxacin concentrations (1–16 MBCs). Studies on electron microscopy demonstrated that singular cells were rapidly destroyed after relatively short-term exposure to moxifloxacin, while cells in aggregates or clumps persisted longer, explaining the delayed biocidal…
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