The synergism of the antibacterial action of lysostaphin and warnerin, an antibacterial peptide of the epilancin group, against <i>Staphylococcus aureus</i>

Aleksandr Lobanov; Ekaterina Yaburova; Daria Eroshenko; Tatyana Polyudova; Aleksandr Lobanov; Ekaterina Yaburova; Daria Eroshenko; Tatyana Polyudova

doi:10.3934/microbiol.2026033

AIMS Microbiology

2026, Volume 12, Issue 4: 774-788. doi: 10.3934/microbiol.2026033

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Research article

The synergism of the antibacterial action of lysostaphin and warnerin, an antibacterial peptide of the epilancin group, against Staphylococcus aureus

Institute of Ecology and Genetics of Microorganisms, Perm, Russian Federation

Received: 04 May 2026 Revised: 15 October 2026 Accepted: 19 October 2026 Published: 29 October 2026

Whole-genome sequencing of Staphylococcus warneri KL-1 (GenBank GCA_056393345.1) confirmed that this strain harbors a biosynthetic gene cluster encoding epilancins, a class I antimicrobial peptide known as a lantibiotic. The peptide warnerin produced by this strain belongs to the epilancin group and has a high degree of homology with epilancin A37, with a single substitution at position 8 (Val→Ile). Three studied Staphylococcus aureus strains, including MRSA, exhibited low sensitivity to warnerin (MICs 83.38–166.75 µM) and moderate sensitivity to lysostaphin (LS) (MICs 0.15–0.29 µM). However, the combination of LS and warnerin reduced the MIC of warnerin by 16-fold and that of LS by 16–32-fold, depending on the strain. Compared with untreated cells, exposure to subMIC warnerin did not affect cell viability but increased the release of K⁺, ATP, and RNA, indicating disruption of membrane integrity. The synergistic interaction between warnerin and LS was confirmed by the fractional inhibitory concentration index and isobologram analyses and was associated with enhanced cell damage. The bactericidal effect of the combination was demonstrated using a time-kill assay. Morphological changes in S. aureus cells under the influence of warnerin, LS, and their combination were demonstrated via confocal microscopy and AFM.
- warnerin,
- synergism,
- pore formation,
- isobologram analysis,
- confocal microscopy,
- fractional inhibitory concentration
Citation: Aleksandr Lobanov, Ekaterina Yaburova, Daria Eroshenko, Tatyana Polyudova. The synergism of the antibacterial action of lysostaphin and warnerin, an antibacterial peptide of the epilancin group, against Staphylococcus aureus[J]. AIMS Microbiology, 2026, 12(4): 774-788. doi: 10.3934/microbiol.2026033

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Abstract

Whole-genome sequencing of Staphylococcus warneri KL-1 (GenBank GCA_056393345.1) confirmed that this strain harbors a biosynthetic gene cluster encoding epilancins, a class I antimicrobial peptide known as a lantibiotic. The peptide warnerin produced by this strain belongs to the epilancin group and has a high degree of homology with epilancin A37, with a single substitution at position 8 (Val→Ile). Three studied Staphylococcus aureus strains, including MRSA, exhibited low sensitivity to warnerin (MICs 83.38–166.75 µM) and moderate sensitivity to lysostaphin (LS) (MICs 0.15–0.29 µM). However, the combination of LS and warnerin reduced the MIC of warnerin by 16-fold and that of LS by 16–32-fold, depending on the strain. Compared with untreated cells, exposure to subMIC warnerin did not affect cell viability but increased the release of K⁺, ATP, and RNA, indicating disruption of membrane integrity. The synergistic interaction between warnerin and LS was confirmed by the fractional inhibitory concentration index and isobologram analyses and was associated with enhanced cell damage. The bactericidal effect of the combination was demonstrated using a time-kill assay. Morphological changes in S. aureus cells under the influence of warnerin, LS, and their combination were demonstrated via confocal microscopy and AFM.

Acknowledgments

This research was carried out on the basis of the Center for Collective Use “Research of Materials and Substances” of the Perm Federal Research Center, Ural Branch of the Russian Academy of Sciences. The authors acknowledge the Interdisciplinary Center for Shared Facilities of Kazan Federal University for performing whole-genome sequencing.

This work was supported by the Ministry of Science and Higher Education of the Russian Federation (124020500028-4).

Conflict of interest

The authors declare no conflict of interest.

Author contributions

Aleksandr Lobanov: Writing—original draft, Writing—review & editing, Investigation, Formal analysis, Data curation, Visualization. Ekaterina Yaburova: Writing—review & editing, Formal analysis. Daria Eroshenko: Writing—review & editing, Conceptualization. Tatyana Polyudova: Writing—original draft, Writing—review & editing, Supervision, Resources, Methodology, Investigation.

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