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Cited by 3Antimicrobial Peptides and ActivitiesBacterial Genetics and BiotechnologyAdvanced Electron Microscopy Techniques and Applications

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Structural insights into Cir-mediated killing by the antimicrobial protein Microcin V

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Maurakis, Stavros A., O’Donnell, Angela C., Botos, Istvan, Ghirlando, Rodolfo, Davies, Bryan W., Buchanan, Susan K.·2025·Communications Biology
DOI 10.1038/s42003-025-08846-7PMC PMC12511343

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Abstract

Drug-resistant bacteria are a global concern. Novel treatments are needed, but are difficult to develop for Gram-negative species due to the need to traverse the outer membrane to reach targets beneath. A promising solution is found in natural antibiotics which bind outer membrane receptors and co-opt them for import. Exploring this mechanism may open avenues for antibiotic development. An underappreciated class of natural antibiotics are microcins - small antimicrobial proteins secreted by certain bacteria during inter-species competition. Microcins bind outer-membrane receptors of prey species for passage into the periplasm. They have potent activity, bind specific targets, and can control pathobiont expansion and colonization. One microcin, MccV, utilizes the E. coli colicin Ia receptor, Cir, for import. Here, we report the first high-resolution structure of the Cir/MccV complex by Cryo-EM, revealing an interaction centered on an electropositive cavity within the Cir extracellular loops. We also report the affinity of MccV for Cir. Lastly, we mutagenized interacting residues and identified key contacts critical to MccV binding, import, and bacteriolysis. Future efforts may help disentangle the mechanisms of microcin killing and will assess relationships between other microcins and their targets to better understand the potential for microcins to be used as antibacterial drugs.

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Metadata

Authors
Maurakis, S. A., O’Donnell, A. C., Botos, I., Ghirlando, R., Davies, B. W., & Buchanan, S. K.
Affiliations
  • National Institutes of Health (US)
  • The University of Texas at Austin (US)
Corresponding author
  • Davies, Bryan W.
  • Buchanan, Susan K.
ORCID
Venue
Communications Biology
Publisher
Springer Science and Business Media LLC
Published
2025-10-09
Volume
8
Issue
1
Pages
1449-1449
ISSN
2399-3642 (ISSN-L)
DOI
10.1038/s42003-025-08846-7
PMC
PMC12511343
OpenAlex
W4414983066
Cited by
3
References
5
Citations by year
2026: 3
FWCI
1.64
Type
journal article
Language
en
Open access
Licence
Locations
  • Communications Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (ZIA DK011011-19 LMB)
Topics
  • Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
Keywords
outer membrane receptor, natural antibiotics, bacterial lysis, binding affinity, Escherichia coli, Gram-negative bacteria, antibacterial drug development, drug-resistant bacteria

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