Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

Scientific Reports
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. scientific reports
  3. articles
  4. article
Staphylococcus capitis strain producing dual bacteriocins, capidermicin and micrococcin P1, shows broad-spectrum antimicrobial activity
Download PDF
Download PDF
  • Article
  • Open access
  • Published: 31 January 2026

Staphylococcus capitis strain producing dual bacteriocins, capidermicin and micrococcin P1, shows broad-spectrum antimicrobial activity

  • Keijuro Ohdan1,2,
  • Yujin Suzuki2,
  • Miki Kawada-Matsuo2,4,
  • Toshinori Hara5,
  • Mi Nguyen-Tra Le6,
  • Takaya Segawa3,4,
  • Junzo Hisatsune3,4,
  • Yo Sugawara3,
  • Seiya Kashiyama5,
  • Hiroki Ohge4,7,
  • Motoyuki Sugai3,4,
  • Tomonao Aikawa1 &
  • …
  • Hitoshi Komatsuzawa2,4 

Scientific Reports , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Biotechnology
  • Microbiology

Abstract

Antimicrobial-resistant bacteria have become a global concern, necessitating the development of novel antimicrobial agents. Bacteriocins, antimicrobial peptides produced by bacteria, are promising candidates. In this study, we screened Staphylococcus capitis isolates to identify bacteriocins effective against methicillin-resistant Staphylococcus aureus (MRSA). We discovered that one strain, HBC3, exhibited strong activity against Gram-positive bacteria, including MRSA. Genome analysis revealed a unique plasmid encoding two bacteriocin synthesis genes: capidermicin, a class II bacteriocin, and micrococcin P1 (MP1), a thiopeptide. MP1 was first identified in S. capitis. Loss of the plasmid abolished the antibacterial activity. We purified both peptides and evaluated their spectrum of activity. MP1 showed broad activity, especially against Gram-positive cocci, whereas capidermicin was active mainly against Gram-positive rods. These findings demonstrate that S. capitis HBC3 harbors a plasmid encoding two distinct bacteriocins with complementary antibacterial spectra, highlighting the cooperative potential of bacteriocins in combating resistant bacteria.

Data availability

The complete genome of *S. capitis* HBC3 has been deposited in the National Center for Biotechnology Information (NCBI) database under accession number SRR33407742 (Bioproject: PRJNA1258066).

Materials availability

This study did not generate new unique reagents.

Abbreviations

MRSA:

Methicillin-resistant Staphylococcus aureus

VRE:

Vancomycin-resistant enterococci

MP1:

Micrococcin P1

HPLC:

High-performance liquid chromatography

ESI-MS:

Electrospray ionization mass spectrometry

References

  1. GBD 2021 Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050. Lancet 404, 1199–1226 (2024).

    Google Scholar 

  2. Karaman, R., Jubeh, B. & Breijyeh, Z. Resistance of Gram-Positive bacteria to current antibacterial agents and overcoming approaches. Molecules 25, (2020).

  3. Sousa, S. A. et al. Bacterial nosocomial infections: multidrug resistance as a trigger for the development of novel antimicrobials. Antibiotics (Basel) 10, (2021).

  4. Wong, J. W. et al. Prevalence and risk factors of community-associated methicillin-resistant Staphylococcus aureus carriage in Asia-Pacific region from 2000 to 2016: a systematic review and meta-analysis. Clin. Epidemiol. 10, 1489–1501 (2018).

    Google Scholar 

  5. Nakaminami, H. Molecular epidemiological features of Methicillin-Resistant Staphylococcus aureus in Japan. Biol. Pharm. Bull. 48, 196–204 (2025).

    Google Scholar 

  6. Tsiodras, S. et al. Linezolid resistance in a clinical isolate of Staphylococcus aureus. Lancet 358, 207–208 (2001).

    Google Scholar 

  7. Munita, J. M., Bayer, A. S. & Arias, C. A. Evolving resistance among Gram-positive pathogens. Clin. Infect. Dis. 61 (Suppl 2), S48–57 (2015).

    Google Scholar 

  8. Harada, Y. et al. Nosocomial spread of meticillin-resistant Staphylococcus aureus with β-lactam-inducible Arbekacin resistance. J. Med. Microbiol. 63, 710–714 (2014).

    Google Scholar 

  9. Shariati, A. et al. Global prevalence and distribution of Vancomycin resistant, Vancomycin intermediate and heterogeneously Vancomycin intermediate Staphylococcus aureus clinical isolates: a systematic review and meta-analysis. Sci. Rep. 10, 12689 (2020).

    Google Scholar 

  10. Wu, Q. et al. Systematic review and meta-analysis of the epidemiology of vancomycin-resistance Staphylococcus aureus isolates. Antimicrob. Resist. Infect. Control. 10, 101 (2021).

    Google Scholar 

  11. Faron, M. L., Ledeboer, N. A. & Buchan, B. W. Resistance Mechanisms, Epidemiology, and approaches to screening for Vancomycin-Resistant Enterococcus in the health care setting. J. Clin. Microbiol. 54, 2436–2447 (2016).

    Google Scholar 

  12. Cotter, P. D., Hill, C. & Ross, R. P. Bacteriocins: developing innate immunity for food. Nat. Rev. Microbiol. 3, 777–788 (2005).

    Google Scholar 

  13. Jack, R. W., Tagg, J. R. & Ray, B. Bacteriocins of gram-positive bacteria. Microbiol. Rev. 59, 171–200 (1995).

    Google Scholar 

  14. Nisar, S., Shah, A. H. & Nazir, R. The clinical praxis of bacteriocins as natural anti-microbial therapeutics. Arch. Microbiol. 206, 451 (2024).

    Google Scholar 

  15. Bastos, M. C. F., Ceotto, H., Coelho, M. L. V. & Nascimento, J. S. Staphylococcal antimicrobial peptides: relevant properties and potential biotechnological applications. Curr. Pharm. Biotechnol. 10, 38–61 (2009).

    Google Scholar 

  16. Suzuki, Y. et al. The two-component regulatory systems GraRS and SrrAB mediate Staphylococcus aureus susceptibility to Pep5 produced by clinical isolate of Staphylococcus epidermidis. Appl. Environ. Microbiol. 90, e0030024 (2024).

    Google Scholar 

  17. Nakazono, K. et al. Complete sequences of epidermin and Nukacin encoding plasmids from oral-derived Staphylococcus epidermidis and their antibacterial activity. PLoS One. 17, e0258283 (2022).

    Google Scholar 

  18. Kumar, R., Jangir, P. K., Das, J., Taneja, B. & Sharma, R. Genome analysis of Staphylococcus capitis TE8 reveals repertoire of antimicrobial peptides and adaptation strategies for growth on human skin. Sci. Rep. 7, 10447 (2017).

    Google Scholar 

  19. O’Sullivan, J. N. et al. Nisin J, a novel natural Nisin Variant, is produced by Staphylococcus capitis sourced from the human skin microbiota. J Bacteriol 202, (2020).

  20. Lynch, D. et al. Identification and characterisation of capidermicin, a novel bacteriocin produced by Staphylococcus capitis. PLoS One. 14, e0223541 (2019).

    Google Scholar 

  21. Fernández-Fernández, R. et al. Genomic analysis of Bacteriocin-Producing staphylococci: high prevalence of lanthipeptides and the micrococcin P1 biosynthetic gene clusters. Probiotics Antimicrob. Proteins. 17, 159–174 (2025).

    Google Scholar 

  22. Liu, Y. et al. Skin microbiota analysis-inspired development of novel anti-infectives. Microbiome 8, 85 (2020).

    Google Scholar 

  23. Wan, Y. et al. Complete genome assemblies and antibiograms of 22 Staphylococcus capitis isolates. BMC Genom Data. 26, 12 (2025).

    Google Scholar 

  24. Fernández-Fernández, R. et al. Detection and evaluation of the antimicrobial activity of micrococcin P1 isolated from commensal and environmental Staphylococcal isolates against MRSA. Int. J. Antimicrob. Agents. 62, 106965 (2023).

    Google Scholar 

  25. de Freire Bastos, M. C., Miceli de Farias, F., Carlin Fagundes, P. & Varella Coelho, M. L. Staphylococcins: an update on antimicrobial peptides produced by Staphylococci and their diverse potential applications. Appl. Microbiol. Biotechnol. 104, 10339–10368 (2020).

    Google Scholar 

  26. Ovchinnikov, K. V. et al. A strong synergy between the thiopeptide bacteriocin micrococcin P1 and rifampicin against MRSA in a murine skin infection model. Front. Immunol. 12, 676534 (2021).

    Google Scholar 

  27. Ongpipattanakul, C. et al. Mechanism of action of ribosomally synthesized and Post-Translationally modified peptides. Chem. Rev. 122, 14722–14814 (2022).

    Google Scholar 

  28. Ciufolini, M. A. & Lefranc, D. Micrococcin P1: structure, biology and synthesis. Nat. Prod. Rep. 27, 330–342 (2010).

    Google Scholar 

  29. Liu, Y. et al. Essential role of membrane vesicles for biological activity of the bacteriocin micrococcin P1. J. Extracell. Vesicles. 11, e12212 (2022).

    Google Scholar 

  30. Reifsteck, F., Wee, S. & Wilkinson, B. J. Hydrophobicity-hydrophilicity of Staphylococci. J. Med. Microbiol. 24, 65–73 (1987).

    Google Scholar 

  31. Rawlinson, L. A. B., O’Gara, J. P., Jones, D. S. & Brayden, D. J. Resistance of Staphylococcus aureus to the cationic antimicrobial agent poly(2-(dimethylamino ethyl)methacrylate) (pDMAEMA) is influenced by cell-surface charge and hydrophobicity. J. Med. Microbiol. 60, 968–976 (2011).

    Google Scholar 

  32. Li, M. et al. Lethal hydroxyl radical accumulation by a lactococcal bacteriocin, lacticin Q. Antimicrob. Agents Chemother. 57, 3897–3902 (2013).

    Google Scholar 

  33. Netz, D. J. A., Bastos, M. do C. de F. & Sahl, H.-G. Mode of action of the antimicrobial peptide Aureocin A53 from Staphylococcus aureus. Appl. Environ. Microbiol. 68, 5274–5280 (2002).

    Google Scholar 

  34. Lynch, D., Hill, C., Field, D. & Begley, M. Inhibition of Listeria monocytogenes by the Staphylococcus capitis - derived bacteriocin capidermicin. Food Microbiol. 94, 103661 (2021).

    Google Scholar 

  35. Brdová, D., Ruml, T. & Viktorová, J. Mechanism of Staphylococcal resistance to clinically relevant antibiotics. Drug Resist. Updat. 77, 101147 (2024).

    Google Scholar 

  36. Nam, E. Y. et al. Emergence of Daptomycin-Nonsusceptible Methicillin-Resistant Staphylococcus aureus clinical isolates among Daptomycin-Naive patients in Korea. Microb. Drug Resist. 24, 534–541 (2018).

    Google Scholar 

  37. Ernst, C. M. & Peschel, A. MprF-mediated daptomycin resistance. Int. J. Med. Microbiol. 309, 359–363 (2019).

    Google Scholar 

  38. Siguier, P., Gourbeyre, E. & Chandler, M. Bacterial insertion sequences: their genomic impact and diversity. FEMS Microbiol. Rev. 38, 865–891 (2014).

    Google Scholar 

  39. Varani, A., He, S., Siguier, P., Ross, K. & Chandler, M. The IS6 family, a clinically important group of insertion sequences including IS26. Mob. DNA. 12, 11 (2021).

    Google Scholar 

  40. Partridge, S. R., Kwong, S. M., Firth, N. & Jensen, S. O. Mobile genetic elements associated with antimicrobial resistance. Clin Microbiol. Rev 31, (2018).

  41. Memariani, H., Memariani, M., Eskandari, S. E. & Ghasemian, A. Nour Neamatollahi, A. The potential role of probiotics and their bioactive compounds in the management of pulmonary tuberculosis. J. Infect. Public. Health. 18, 102840 (2025).

    Google Scholar 

  42. Roy, S. & Dhaneshwar, S. Role of prebiotics, probiotics, and synbiotics in management of inflammatory bowel disease: current perspectives. World J. Gastroenterol. 29, 2078–2100 (2023).

    Google Scholar 

  43. Kommineni, S. et al. Bacteriocin production augments niche competition by enterococci in the mammalian Gastrointestinal tract. Nature 526, 719–722 (2015).

    Google Scholar 

  44. Laurent, F. & Butin, M. Staphylococcus capitis and NRCS-A clone: the story of an unrecognized pathogen in neonatal intensive care units. Clin. Microbiol. Infect. 25, 1081–1085 (2019).

    Google Scholar 

  45. Cotter, P. D., Ross, R. P. & Hill, C. Bacteriocins - a viable alternative to antibiotics? Nat. Rev. Microbiol. 11, 95–105 (2013).

    Google Scholar 

  46. Kusaka, S. et al. Oral and rectal colonization of methicillin-resistant Staphylococcus aureus in long-term care facility residents and their association with clinical status. Microbiol. Immunol. 68, 75–89 (2024).

    Google Scholar 

  47. Kawayanagi, T. et al. The oral cavity is a potential reservoir of gram-negative antimicrobial-resistant bacteria, which are correlated with ageing and the number of teeth. Heliyon 10, e39827 (2024).

    Google Scholar 

  48. Wick, R. R., Judd, L. M., Gorrie, C. L. & Holt, K. E. Unicycler: resolving bacterial genome assemblies from short and long sequencing reads. PLoS Comput. Biol. 13, e1005595 (2017).

    Google Scholar 

  49. van Heel, A. J. et al. BAGEL4: a user-friendly web server to thoroughly mine RiPPs and bacteriocins. Nucleic Acids Res. 46, W278–W281 (2018).

    Google Scholar 

  50. Blin, K. et al. AntiSMASH 7.0: new and improved predictions for detection, regulation, chemical structures and visualisation. Nucleic Acids Res. 51, W46–W50 (2023).

    Google Scholar 

  51. Alikhan, N. F., Petty, N. K., Zakour, B., Beatson, S. A. & N. L. & BLAST ring image generator (BRIG): simple prokaryote genome comparisons. BMC Genom. 12, 402 (2011).

    Google Scholar 

  52. Sullivan, M. J., Petty, N. K. & Beatson, S. A. Easyfig: a genome comparison visualizer. Bioinformatics 27, 1009–1010 (2011).

    Google Scholar 

  53. Ersfeld-Dressen, H., Sahl, H. G. & Brandis, H. Plasmid involvement in production of and immunity to the staphylococcin-like peptide Pep 5. J. Gen. Microbiol. 130, 3029–3035 (1984).

    Google Scholar 

Download references

Acknowledgements

Conceptualization: Data curation: Formal analysis: Funding acquisition: Investigation: Methodology: Project Administration: Resources: Software: Supervision: Validation: Visualization: Writing-original draft: Writing-review and editing: We declare that there are no conflicts of interest.We thank Dr. Tomoko Amimoto, the Natural Science Center for Basic Research and Development (N-BARD), Hiroshima University for the measurement of ESI-MS analysis.

Funding

This study was supported in part by a Grant-in-Aid for Scientific Research (C) (Grant No. 21K12886) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by the Japan Agency for Medical Research and Development (AMED) under Grant Numbers JP23fk0108606 and JP25fk0108699.

Author information

Authors and Affiliations

  1. Department of Oral and Maxillofacial surgery, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan

    Keijuro Ohdan & Tomonao Aikawa

  2. Department of Bacteriology, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima-shi, Hiroshima Prefecture, 734-8551, Japan

    Keijuro Ohdan, Yujin Suzuki, Miki Kawada-Matsuo & Hitoshi Komatsuzawa

  3. Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security, Higashi Murayama, Japan

    Takaya Segawa, Junzo Hisatsune, Yo Sugawara & Motoyuki Sugai

  4. Project Research Centre for Nosocomial Infectious Diseases, Hiroshima University, Hiroshima, Japan

    Miki Kawada-Matsuo, Takaya Segawa, Junzo Hisatsune, Hiroki Ohge, Motoyuki Sugai & Hitoshi Komatsuzawa

  5. Section of Clinical Laboratory, Division of Clinical Support, Hiroshima University Hospital, Hiroshima, Japan

    Toshinori Hara & Seiya Kashiyama

  6. Faculty of Dentistry, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam

    Mi Nguyen-Tra Le

  7. Department of Infectious Diseases, Hiroshima University Hospital, Hiroshima, Japan

    Hiroki Ohge

Authors
  1. Keijuro Ohdan
    View author publications

    Search author on:PubMed Google Scholar

  2. Yujin Suzuki
    View author publications

    Search author on:PubMed Google Scholar

  3. Miki Kawada-Matsuo
    View author publications

    Search author on:PubMed Google Scholar

  4. Toshinori Hara
    View author publications

    Search author on:PubMed Google Scholar

  5. Mi Nguyen-Tra Le
    View author publications

    Search author on:PubMed Google Scholar

  6. Takaya Segawa
    View author publications

    Search author on:PubMed Google Scholar

  7. Junzo Hisatsune
    View author publications

    Search author on:PubMed Google Scholar

  8. Yo Sugawara
    View author publications

    Search author on:PubMed Google Scholar

  9. Seiya Kashiyama
    View author publications

    Search author on:PubMed Google Scholar

  10. Hiroki Ohge
    View author publications

    Search author on:PubMed Google Scholar

  11. Motoyuki Sugai
    View author publications

    Search author on:PubMed Google Scholar

  12. Tomonao Aikawa
    View author publications

    Search author on:PubMed Google Scholar

  13. Hitoshi Komatsuzawa
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Conceptualization: Yu.S., M.K.-M. and H.K. Data curation: K.O., Yu.S. and H.K. Formal analysis: K.O. and Yu.S. Funding acquisition: M.K.-M., M.S. and H.K. Investigation: K.O., Yu.S., T.H., M.N.-T.L., J.H., Yo. S., and H.K. Methodology: Yu.S., M.K.-M., and H.K. Project Administration: M.K.-M., T.A. and H.K. Resources: M.K.-M., J.H., M.S. and H.K. Software: Yu.S., M.K.-M. and M.N.-T.L. Supervision: M.K.-M., M.S., S.K., H.O., T.A. and H.K. Validation: K.O., Yu.S. and H.K. Visualization: K.O. and Yu.S. Writing-original draft: K.O., Yu.S. and H.K. Writing-review and editing: All authors.

Corresponding authors

Correspondence to Miki Kawada-Matsuo or Hitoshi Komatsuzawa.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ohdan, K., Suzuki, Y., Kawada-Matsuo, M. et al. Staphylococcus capitis strain producing dual bacteriocins, capidermicin and micrococcin P1, shows broad-spectrum antimicrobial activity. Sci Rep (2026). https://doi.org/10.1038/s41598-026-36393-6

Download citation

  • Received: 13 August 2025

  • Accepted: 12 January 2026

  • Published: 31 January 2026

  • DOI: https://doi.org/10.1038/s41598-026-36393-6

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Keywords

  • Antimicrobial peptide
  • Bacteriocin
  • Staphylococcus capitis
  • Capidermicin
  • Micrococcin P1
  • MRSA
Download PDF

Associated content

Collection

Next-generation antimicrobial agents

Advertisement

Explore content

  • Research articles
  • News & Comment
  • Collections
  • Subjects
  • Follow us on Facebook
  • Follow us on Twitter
  • Sign up for alerts
  • RSS feed

About the journal

  • About Scientific Reports
  • Contact
  • Journal policies
  • Guide to referees
  • Calls for Papers
  • Editor's Choice
  • Journal highlights
  • Open Access Fees and Funding

Publish with us

  • For authors
  • Language editing services
  • Open access funding
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

Scientific Reports (Sci Rep)

ISSN 2045-2322 (online)

nature.com sitemap

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2026 Springer Nature Limited

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research