Examination of yield, bacteriolytic activity and cold storage of linker deletion mutants based on endolysin S6_ORF93 derived from Staphylococcus giant bacteriophage S6

PLoS One. 2024 Oct 23;19(10):e0310962. doi: 10.1371/journal.pone.0310962. eCollection 2024.

Abstract

Methicillin-resistant Staphylococcus spp. present challenges in clinical and veterinary settings because effective antimicrobial agents are limited. Phage-encoded peptidoglycan-degrading enzyme, endolysin, is expected to be a novel antimicrobial agent. The enzymatic activity has recently been shown to be influenced by the linker between functional domains in the enzyme. S6_ORF93 (ORF93) is one of the endolysins derived from previously isolated Staphylococcus giant phage S6. The ORF93 was speculated to have a catalytic and peptidoglycan-binding domain with a long linker. In this study, we examined the influence of linker shortening on the characteristics of ORF93. We produce wild-type ORF93 and the linker deletion mutants using an Escherichia coli expression system. These mutants were designated as ORF93-Δ05, ORF93-Δ10, ORF93-Δ15, and ORF93-Δ20, from which 5, 10, 15, and 20 amino acids were removed from the linker, respectively. Except for the ORF93-Δ20, ORF93 and its mutants were expressed as soluble proteins. Moreover, ORF93-Δ15 showed the highest yield and bacteriolytic activity, while the antimicrobial spectrum was homologous. The cold storage experiment showed a slight effect by the linker deletion. According to our results and other studies, linker investigations are crucial in endolysin development.

MeSH terms

  • Bacteriolysis
  • Cold Temperature
  • Endopeptidases* / chemistry
  • Endopeptidases* / genetics
  • Endopeptidases* / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / virology
  • Sequence Deletion*
  • Staphylococcus Phages / genetics
  • Viral Proteins / chemistry
  • Viral Proteins / genetics
  • Viral Proteins / metabolism

Substances

  • endolysin
  • Endopeptidases
  • Viral Proteins

Grants and funding

This work was funded by a joint research fund from Nippon Zenyaku Kogyo Co. Ltd. (https://www.zenoaq.com/). J.U. has received this funding. There is no specific grant number. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.