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Slow growth for bacterial persistence
Even bacteria that do not carry mutations or genes that confer resistance to specific antibiotics can survive antibiotic treatment, a phenomenon known as persistence (see the Focus by Kaldalu and Tenson). Several models have been proposed to account for bacterial persistence, including the activation of toxins in toxin-antitoxin modules, the production of the alarmone guanosine (penta) tetraphosphate [(p)ppGpp], and a reduction in intracellular adenosine triphosphate (ATP) abundance. Pontes and Groisman demonstrated that Salmonella exhibited persistence even in the absence of toxin-antitoxin modules or (p)ppGpp production and under conditions that increased intracellular ATP. These and additional findings show that slow growth alone is sufficient for persistence and may contribute to the difficulty in treating some bacterial infections.
Abstract
Bacteria can withstand killing by bactericidal antibiotics through phenotypic changes mediated by their preexisting genetic repertoire. These changes can be exhibited transiently by a large fraction of the bacterial population, giving rise to tolerance, or displayed by a small subpopulation, giving rise to persistence. Apart from undermining the use of antibiotics, tolerant and persistent bacteria foster the emergence of antibiotic-resistant mutants. Persister formation has been attributed to alterations in the abundance of particular proteins, metabolites, and signaling molecules, including toxin-antitoxin modules, adenosine triphosphate, and guanosine (penta) tetraphosphate, respectively. Here, we report that persistent bacteria form as a result of slow growth alone, despite opposite changes in the abundance of such proteins, metabolites, and signaling molecules. Our findings argue that transitory disturbances to core activities, which are often linked to cell growth, promote a persister state regardless of the underlying physiological process responsible for the change in growth.
