Bacteriophages that infect Gram-negative bacteria as source of signal-arrest-release motif lysins

Author(s)

Pardini Gontijo, Marco Tulio ^[1] ; Pereira Vidigal, Pedro Marcus ^[2] ; Soto Lopez, Maryoris Elisa ^[3] ; Brocchi, Marcelo ^[1]

Affiliation

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

^[2] Univ Fed Vicosa UFV, Brazil Elect Address Pmvidigal Gmailcom, Vila Gianetti, Casa 21, Campus UFV, BR-36570900 Vicosa, MG - Brazil

^[3] Univ Cordoba UNICORDOBA, Dept Ingn Alimentos, Carrera 6 77-305, Monteria 230002 - Colombia

• Document type: Journal article
• Source: Research in Microbiology; v. 172, n. 2 MAR 2021.
• Web of Science Citations: 0

Abstract

Treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria is challenging, a potential solution for which is the use of bacteriophage-derived lytic enzymes. However, the exogenous action of bacteriophage lysins against Gram-negative bacteria is hindered due to the presence of an impermeable outer membrane in these bacteria. Nevertheless, recent research has demonstrated that some lysins are capable of permeating the outer membrane of Gram-negative bacteria with the help of signal peptides. In the present study, we investigated the genomes of 309 bacteriophages that infect Gram-negative pathogens of clinical interest in order to determine the evolutionary markers of signal peptide-containing lysins. Complete genomes displayed 265 putative lysins, of which 17 (6.41%) con-tained signal-arrest-release motifs and 41 (15.47%) contained cleavable signal peptides. There was no apparent relationship between host specificity and lysin diversity. Nevertheless, the evolution of lysin genes might not be independent of the rest of the bacteriophage genome once pan-genome clustering and lysin diversity appear to be correlated. In addition, signal peptide-and signal-arrest-release-containing lysins were monophyletically distributed in the protein cladogram, suggesting that the nat-ural selection of holin-independent lysins is divergent. Our study screened 58 (21.89%) out of 265 po-tential candidates for in vitro experimentation against MDR bacteria. (c) 2020 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. (AU)

• 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
• 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