Artilysins are a novel, promising class of antibacterials based on bacteriophage-encoded endolysins. Endolysins are produced at the end of the lytic replication cycle. Once the endolysins have passed through pores formed by holins in the cytoplasmic membrane, they degrade the peptidoglycan layer rapidly, causing osmotic lysis of the infected cell and liberation of the progeny. Purified endolysins have successfully been exploited to kill Gram-positive pathogens. However, Gram-negative bacteria are not susceptible due to the presence of a protective outer membrane.

Artilysins tackle this barrier. Selected polycationic or amphipathic peptides that locally destabilize the LPS layer of the outer membrane have been covalently fused to endolysins. These peptides promote the transfer of the fused endolysin to the peptidoglycan layer through the outer membrane. Time-lapse microscopy has shown that cells are killed within seconds due to active peptidoglycan degradation and subsequent cell lysis. Artilysins are highly bactericidal, irrespective the presence of drug resistance mechanisms, show a low probability of resistance development, and have unprecedented bactericidal activity against bacterial persisters. Their in vivo activity has been reported against otitis in dog case studies.