Nutrient depletion and bacterial persistence

Most antibiotics do not work well on starving bacteria. In environments that are missing one or more essential nutrient, bacteria shut down the growth-related processes that most antibiotics target and ready themselves for stressful times. Such nutrient-depleted conditions can occur within a host, and they are prevalent within biofilms. For antibiotics that retain some bactericidal activity against starved populations, treatments of those cultures often leave many persisters, which can go on to spawn new populations. Persisters are bacterial cells with non-inherited abilities to survive antibiotic treatments that kill the majority of their genetically identical kin. The capacity of persisters to tolerate such treatments originates from phenotypic differences between them and the bacteria that die, and understanding those survival mechanisms promises to improve treatments for chronic and recurring infections. Here we review knowledge of bacterial starvation physiology and provide an overview of nutritional challenges bacteria face in the host and in biofilms. We then describe those antibiotic classes with the capacity to kill nutrient-deprived bacteria and summarize understanding of persistence in those populations. Finally, we discuss approaches that could be used to develop treatments that eradicate starved bacterial populations and the persisters within them.