Bacteriophage Endolysins as a Novel Class of Antibacterial Agents

Abstract

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.

Characterization and Detection of Endolysin Gene from Three Acinetobacter baumannii Bacteriophages Isolated from Sewage Water

“…Bacteriophages are able to replicate in the host cell and produce endolysin to lyse the host cell. Endolysin is a phage peptidoglycan hydrolases produced in the lytic cycle that degrades the bacterial cell wall [10,11]. Phage endolysins have been studied in a variety of pathogenic bacteria including A. baumannii for theirs antibacterial activity [11][12][13].…”

Bacteriophage biocontrol of foodborne pathogens

“…Lysins are enzymes produced by lytic phages, which play role in the degradation of the bacterial cell wall through targeting its various peptidoglycan bonds to allow the newly formed progeny phages to be released from the host cell (Borysowski et al 2006). Because lysin enzymes attacks the cell wall peptidoglycan, they are highly effective against Gram-positive bacteria when added externally and may be used as biocontrol agents to enhance food safety (Fischetti 2008).…”

“…Forty-eight strains of Clostridium perfringens were lysed by murein hydrolase (lysin) enzyme that is produced by C. perfringens phage j3626 (Zimmer et al 2002). Another technique of using lyisn is via lysin-secreting recombinant bacteria (Borysowski et al 2006). This was demonstrated in the case of recombinant Lactococcus lactis cells containing listerial lysin encoding genes to lyse L. monocytogenes in the surrounding medium (Gaeng et al 2000).…”

Enzybiotics and their Potential Applications in Medicine

“…In view of the ever -increasing antibiotic resistance of bacteria, the most important characteristics of enzybiotics are a novel mode of antibacterial action, different from those typical of antibiotics, and the capacity to kill antibiotic -resistant bacteria (Borysowski et al 2006 ). Another signifi cant feature of some lytic enzymes is the low probability of developing bacterial resistance (in some cases, the development of enzybiotic resistance results in a reduction in bacterial fi tness and virulence; Kusuma et al 2007 ).…”

“…Lysins or endolysins are double -stranded DNA bacteriophage -encoded enzymes that cleave covalent bonds in peptidoglycan (Borysowski et al 2006 ;Fischetti 2008 ). They are naturally produced in phageinfected bacterial cells during the course of lytic cycle.…”