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

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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.

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Data Availability

All data generated or analyzed during this study are included in this published article (and its supplementary information files).

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Acknowledgements

MTPG is supported by the Brazilian funding agency Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) through an M.Sc. scholarship (grant 2020/01535-9). MPT is also supported by FAPESP through a scientific initiation scholarship (grant 2020/09815-0). Research in our laboratory is supported by FAPESP (grant 2021/00465-0). MB is a research fellow of the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq – process number: 309380/2019-7).

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Authors and Affiliations

  1. Departamento de Genética, Evolução, Microbiologia e Imunologia, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Cidade Universitária Zeferino Vaz, Rua Monteiro Lobato 255, Campinas, São Paulo, 13083-862, Brazil

    Marco Túlio Pardini Gontijo, Mateus Pereira Teles & Marcelo Brocchi

  2. Faculdade de Farmácia, Universidade Estadual de Campinas (UNICAMP), Cidade Universitária Zeferino Vaz, Rua Cândido Portinari 200, Campinas, São Paulo, 13083-862, Brazil

    Mateus Pereira Teles

  3. Núcleo de Análise de Biomoléculas (NuBioMol), Universidade Federal de Viçosa (UFV), Vila Gianetti, Casa 21, Campus da UFV, Viçosa, Minas Gerais, 36570-900, Brazil

    Pedro Marcus Pereira Vidigal

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  1. Marco Túlio Pardini Gontijo
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  2. Mateus Pereira Teles
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  3. Pedro Marcus Pereira Vidigal
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  4. Marcelo Brocchi
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Contributions

MTPG, MPT, and PMPV conceived and designed the study, performed the analysis, and interpreted the data. MTPG wrote the manuscript. MB contributed to finalizing the manuscript and coordinated the study. All authors read and approved the final text.

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Correspondence to Marco Túlio Pardini Gontijo.

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Gontijo, M.T., Teles, M.P., Vidigal, P.M. et al. Expanding the Database of Signal-Anchor-Release Domain Endolysins Through Metagenomics. Probiotics & Antimicro. Prot. 14, 603–612 (2022). https://doi.org/10.1007/s12602-022-09948-y

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