Taking aim on bacterial pathogens: from phage therapy to enzybiotics.
The bactericidal activity of bacteriophages has been used to treat human infections for years as an alternative or a complement to antibiotic therapy. Nowadays, endolysins (phage-encoded enzymes that break down bacterial peptidoglycan at the terminal stage of the phage reproduction cycle) have been used successfully to control antibiotic-resistant pathogenic bacteria in animal models. Their cell wall binding domains target the enzymes to their substrate, and their corresponding catalytic domains are able to cleave bonds in the peptidoglycan network. Recent research has not only revealed the surprising rich structural catalytic diversity of these murein hydrolases but has also yielded insights into their modular organization, their three-dimensional structures, and their mechanism of recognition of bacterial cell wall. These results allow endolysins to be considered as effective antimicrobials with potentially important applications in medicine and biotechnology.
Hermoso
Juan A
JA
Grupo de Cristalografía Macromolecular y Biología Estructural, Instituto Química-Física Rocasolano, CSIC, Serrano 119, 28006 Madrid, Spain. xjuan@iqfr.csic.es
García
José L
JL
García
Pedro
P
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000166:cytology / Q000187:drug effects*; D001424:Bacterial Infections / Q000628:therapy; D001433:Bacteriolysis / Q000187:drug effects; D001435:Bacteriophages / Q000201:enzymology*; D002473:Cell Wall / Q000187:drug effects; D010450:Endopeptidases / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000737:chemistry / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity; D014764:Viral Proteins / Q000737:chemistry / Q000494:pharmacology*; D014771:Virion / Q000201:enzymology
D000900:Anti-Bacterial Agents; D014764:Viral Proteins; D010450:Endopeptidases; C001143:endolysin; D009238:N-Acetylmuramoyl-L-alanine Amidase