Use of Bacteriophages to Target Intracellular Pathogens.

Bacteriophages (phages) have shown great potential as natural antimicrobials against extracellular pathogens (eg, Escherichia coli or Klebsiella pneumoniae), but little is known about how they interact with intracellular targets (eg, Shigella spp., Salmonella spp., Mycobacterium spp.) in the mammalian host. Recent research has demonstrated that phages can enter human cells. However, for the design of successful clinical applications, further investigation is required to define their subcellular behavior and to understand the complex biological processes that underlie the interaction with their bacterial targets. In this review, we summarize the molecular evidence of phage internalization in eucaryotic cells, with specific focus on proof of phage activity against their bacterial targets within the eucaryotic host, and the current proposed strategies to overcome poor penetrance issues that may impact therapeutic use against the most clinically relevant intracellular pathogens.