Figure 3.

Repression Displayed by Antibiotic-Tolerant Bacteria Can Be Overcome through Multiple Emerging Approaches

Antibiotic-tolerant bacteria—whether nutrient-limited stationary phase cells, persisters, or biofilms—all display repressed metabolism that contributes to their ability to survive bactericidal antibiotic treatment. Metabolic activation through the use of metabolite adjuvants has been shown to enhance the sensitivity of antibiotic-tolerant bacteria to conventional bactericidal antibiotics. Furthermore, molecules like polymyxins, human cationic peptides, and ADEP4 display bactericidal activity that is independent of the metabolic state of the cell and may represent a promising approach to develop antibiotics that are not impeded by metabolic repression displayed by conventionally antibiotic-tolerant populations. Lastly, engineered phage and bacteria that actively modulate the metabolic response of pathogens to conventional antibiotics may be an alternative approach to eradicate cells in metabolically repressed states.