Heterogeneous Strategies to Eliminate Intracellular Bacterial Pathogens

Antibiotic tolerance in bacterial pathogens that are genetically susceptible, but phenotypically tolerant to treatment, represents a growing crisis for public health. In particular, the intracellular bacteria-mediated antibiotic tolerance by acting as “Trojan horses” play a critical and underappreciated role in the disease burden of bacterial infections. Thus, more intense efforts are required to tackle this problem. In this review, we firstly provide a brief overview of modes of action of bacteria invasion and survival in macrophage or non-professional phagocytic cells. Furthermore, we summarize our current knowledge about promising strategies to eliminate these intracellular bacterial pathogens, including direct bactericidal agents, antibiotic delivery to infection sites by various carriers, and activation of host immune functions. Finally, we succinctly discuss the challenges faced by bringing them into clinical trials and our constructive perspectives.