Fusion to cell-penetrating peptides will enable lytic enzymes to kill intracellular bacteria

Lytic enzymes are proteins that cleave peptidoglycan, the major component of the bacterial cell wall. They are unique antibacterial agents, whose potential medical applications include the elimination of mucosal colonization and the treatment of bacterial infections, especially those caused by Gram-positive bacteria. However, lytic enzymes are capable of killing only extracellular bacteria, while their access to intracellular pathogens is restricted by the plasma membrane of the infected cell. Lytic enzymes' inability to kill intracellular bacteria is likely to diminish their therapeutic efficacy, especially when eliminating bacteria that can undergo internalization in host cells. Here we present our hypothesis that lytic enzymes could kill intracellular bacteria upon their introduction into the cytoplasm of human cells by cell-penetrating peptides. We also discuss potential medical applications of intracellularly active lytic enzymes.