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Experimental Biology and Medicine 231:366-377 (2006)
© 2006 Society for Experimental Biology and Medicine

MINIREVIEW

Bacteriophage Endolysins as a Novel Class of Antibacterial Agents

Jan Borysowski*,1, Beata Weber-Dabrowska{dagger} and Andrzej Górski*,{dagger}

* Department of Clinical Immunology, Institute of Transplantology, The Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, Poland; and {dagger} Laboratory of Bacteriophages, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wroclaw, Poland

To whom requests for reprints should be addressed at 1 Nowogrodzka 59, 02-006 Warsaw, Poland. E-mail: jborysowski{at}interia.pl

Endolysins are double-stranded DNA bacteriophage-encoded peptidoglycan hydrolases produced in phage-infected bacterial cells toward the end of the lytic cycle. They reach the peptidoglycan through membrane lesions formed by holins and cleave it, thus, inducing lysis of the bacterial cell and enabling progeny virions to be released. Endolysins are also capable of degrading peptidoglycan when applied externally (as purified recombinant proteins) to the bacterial cell wall, which also results in a rapid lysis of the bacterial cell. The unique ability of endolysins to rapidly cleave peptidoglycan in a generally species-specific manner renders them promising potential antibacterial agents. Originally developed with a view to killing bacteria colonizing mucous membranes (with the first report published in 2001), endolysins also hold promise for the treatment of systemic infections. As potential antibacterials, endolysins possess several important features, for instance, a novel mode of action, a narrow antibacterial spectrum, activity against bacteria regardless of their antibiotic sensitivity, and a low probability of developing resistance. However, there is only one report directly comparing the activity of an endolysin with that of an antibiotic, and no general conclusions can be drawn regarding whether lysins are more effective than traditional antibiotics. The results of the first preclinical studies indicate that the most apparent potential problems associated with endolysin therapy (e.g., their immunogenicity, the release of proinflammatory components during bacteriolysis, or the development of resistance), in fact, may not seriously hinder their use. However, all data regarding the safety and therapeutic effectiveness of endolysins obtained from preclinical studies must be ultimately verified by clinical trials. This review discusses the prophylactic and therapeutic applications of endolysins, especially with respect to their potential use in human medicine. Additionally, we outline current knowledge regarding the structure and natural function of the enzymes in phage biology, including the most recent findings.

Key Words: bacteriophage • endolysin • antibiotic-resistance • infection






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Copyright © 2006 by the Society for Experimental Biology and Medicine.