Expanding the Database of Signal-Anchor-Release Domain Endolysins Through Metagenomics

Author(s)

Pardini Gontijo, Marco Tulio ; Teles, Mateus Pereira ; Pereira Vidigal, Pedro Marcus ; Brocchi, Marcelo

• Document type: Journal article
• Source: PROBIOTICS AND ANTIMICROBIAL PROTEINS; v. 14, n. 4, p. 10-pg., 2022-05-07.

Abstract

Endolysins are bacteriophage-derived lytic enzymes with antimicrobial activity. The action of endolysins against Gram-negative bacteria remains a challenge due to the physical protection of the outer membrane. However, recent research has demonstrated that signal-anchor-release (SAR) endolysins permeate the outer membrane of Gram-negative bacteria. This study investigates 2628 putative endolysin genes identified in 183,298 bacteriophage genomes. Previously, bioinformatic approaches resulted in a database of 66 SAR endolysins. This manuscript almost doubles the list with 53 additional SAR endolysin candidates. Forty-eight of the putative SAR endolysins described in this study contained one muramidase catalytic domain, and five included additional cell wall-binding domains at the C-terminus. For the moment, SAR domains are found in four protein families: glycoside hydrolase family 19 (GH19), glycoside hydrolase family 24 (GH24), glycoside hydrolase family 25 (GH25), and glycoside hydrolase family 108 (GH108). These SAR lysis are clustered in eight groups based on biochemical properties and domain presence/absence. Therefore, in this study, we expand the arsenal of endolysin candidates that might act against Gram-negative bacteria and develop a consult database for antimicrobial proteins derived from bacteriophages. (AU)

• FAPESP's process: 20/09815-0 - Use of phage endolysins with membrane permeabilizer agents against multi-resistant gram-negative bacteria: a strategy for antibacterial therapy
• Grantee: Mateus Pereira Teles
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 20/01535-9 - Comparative genomics and antimicrobial activity of recombinant phage endolisins against multi-resistant gram-negative bacteria
• Grantee: Marco Túlio Pardini Gontijo
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 21/00465-0 - Genomic, pathogenicity, resistance, antitumoral therapy and vaccines development based on Salmonella enterica
• Grantee: Marcelo Brocchi
• Support Opportunities: Regular Research Grants