Current Status of Endolysin-Based Treatments against Gram-Negative Bacteria

Author(s)

Pardini Gontijo, Marco Tulio ^[1] ; Jorge, Genesy Perez ^[1] ; Brocchi, Marcelo ^[1]

Affiliation

^[1] Univ Estadual Campinas, Inst Biol, Dept Genet Evolucao Microbiol & Imunol, UNICAMP, Rua Monteiro Lobato 255, BR-13083862 Campinas - Brazil

• Document type: Review article
• Source: ANTIBIOTICS-BASEL; v. 10, n. 10 OCT 2021.
• Web of Science Citations: 0

Abstract

The prevalence of multidrug-resistant Gram-negative bacteria is a public health concern. Bacteriophages and bacteriophage-derived lytic enzymes have been studied in response to the emergence of multidrug-resistant bacteria. The availability of tRNAs and endolysin toxicity during recombinant protein expression is circumvented by codon optimization and lower expression levels using inducible pET-type plasmids and controlled cultivation conditions, respectively. The use of polyhistidine tags facilitates endolysin purification and alters antimicrobial activity. Outer membrane permeabilizers, such as organic acids, act synergistically with endolysins, but some endolysins permeate the outer membrane of Gram-negative bacteria per se. However, the outer membrane permeation mechanisms of endolysins remain unclear. Other strategies, such as the co-administration of endolysins with polymyxins, silver nanoparticles, and liposomes confer additional outer membrane permeation. Engineered endolysins comprising domains for outer membrane permeation is also a strategy used to overcome the current challenges on the control of multidrug-resistant Gram-negative bacteria. Metagenomics is a new strategy for screening endolysins with interesting antimicrobial properties from uncultured phage genomes. Here, we review the current state of the art on the heterologous expression of endolysin, showing the potential of bacteriophage endolysins in controlling bacterial infections.</p> (AU)

• 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: 17/10051-2 - Biotechnological potential and phenotypic and molecular characterization of Salmonella enterica mutants
• Grantee: Marcelo Brocchi
• Support Opportunities: Regular Research Grants