Endolysins against Streptococci as an antibiotic alternative

Abstract

Multi-drug resistance has called for a race to uncover alternatives to existing antibiotics. Phage therapy is one of the explored alternatives, including the use of endolysins, which are phage-encoded peptidoglycan hydrolases responsible for bacterial lysis. Endolysins have been extensively researched in different fields, including medicine, food, and agricultural applications. While the target specificity of various endolysins varies greatly between species, this current review focuses specifically on streptococcal endolysins. Streptococcus spp. causes numerous infections, from the common strep throat to much more serious life-threatening infections such as pneumonia and meningitis. It is reported as a major crisis in various industries, causing systemic infections associated with high mortality and morbidity, as well as economic losses, especially in the agricultural industry. This review highlights the types of catalytic and cell wall-binding domains found in streptococcal endolysins and gives a comprehensive account of the lytic ability of both native and engineered streptococcal endolysins studied thus far, as well as its potential application across different industries. Finally, it gives an overview of the advantages and limitations of these enzyme-based antibiotics, which has caused the term enzybiotics to be conferred to it.

Comprehensive Characterization of a Streptococcus agalactiae Phage Isolated from a Tilapia Farm in Selangor, Malaysia, and Its Potential for Phage Therapy

“…Endolysin is a peptidoglycan hydrolase enzyme that cleaves glycosidic, peptide, and/or amide bonds that hold the peptidoglycan structure. It is made up of the catalytic domain (CD) and cell wall-binding domain (CWBD) [ 28 ]. Some endolysins possess more than one CD, where each type of CD could cleave a single type of bond such as endopeptidase and amidase.…”

“…Some endolysins possess more than one CD, where each type of CD could cleave a single type of bond such as endopeptidase and amidase. The CWBD functions to bind to the components of the cell wall so that the enzymatic activity of CD could be initiated [ 28 ]. In addition, the holin protein creates an opening on the cell membrane from within, so that at the end of lytic cycle endolysin could traverse to the outer cell wall and degrade the peptidoglycan layer.…”

LysSYL: a broad-spectrum phage endolysin targeting Staphylococcus species and eradicating S. aureus biofilms

“…Bacteriophage (phage) therapy, which utilizes phage itself or its lytic elements, such as endolysins, has emerged as an important research area in the quest for alternatives to combat the antibiotic-resistance crisis [ 3 , 15 ]. Phages in nature exhibit a high degree of diversity and abundance [ 16 ].…”

“…Moreover, the CD in endolysins may have distinct hydrolase activities, such as cysteine- and histidiane-dependent aminopeptidase/hydrolase (CHAP), N-acetylmuramoyl-L-alanine amidase (amidase 2), muramidase, or glucosaminidase [ 19 ]. Some endolysins carrying certain CDs are highly efficient hydrolases that degrade the peptidoglycan of bacterial cell walls to result in bacterial lysis and death [ 15 ]. Compared with active phages, endolysins offer rapid bactericidal activity and a relatively broad host spectrum [ 17 , 22 ].…”

The therapeutic effect of engineered phage, derived protein and enzymes against superbug bacteria

“…Although using phages to combat bacterial infections has been previously tried in some parts of the world, using endolysins is a relatively new idea showing great promise (Murray et al, 2021). Endolysins have been widely researched in diverse fields, including medicine, food, and agricultural applications (Wong et al, 2022). There are various types of endolysins, and their categorization is based on the structural bonds in the peptidoglycan that are cleaved by the enzyme (Borysowski et al, 2006).…”