Yersinopine is a primary zinc acquisition system for Yersinia pseudotuberculosis

Mahendar Kadari; Casey Weber; Thomas E Kehl-Fie; Robert D Perry; Juan C Ortiz-Marquez; Oleg V Tsodikov; Sylvie Garneau-Tsodikova; Matthew B Lawrenz

doi:10.1128/mbio.02000-26

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Yersinopine is a primary zinc acquisition system for Yersinia pseudotuberculosis

Journal article

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Yersinopine is a primary zinc acquisition system for Yersinia pseudotuberculosis

Mahendar Kadari, Casey Weber, Thomas E Kehl-Fie, Robert D Perry, Juan C Ortiz-Marquez, Oleg V Tsodikov, Sylvie Garneau-Tsodikova and Matthew B Lawrenz

mBio, e0200026

09/17/2026

DOI: 10.1128/mbio.02000-26

PMID: 42752258

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Abstract

Yersinia pestis is a vector-borne pathogen that evolved from the enteric pathogen Yersinia pseudotuberculosis. Despite different routes of infection, both pathogens need to overcome host-mediated zinc limitation. Y. pestis relies on the transporter ZnuABC and the metallophore yersiniabactin, but surprisingly, disruption of these systems in Y. pseudotuberculosis did not limit growth during zinc limitation, suggesting the presence of additional mechanisms. Here, we identify the opine-type metallophore yersinopine, encoded by the cnt operon, as a primary zinc uptake system in Y. pseudotuberculosis. While a znuA ybtX mutant was not attenuated for growth in metal-limited medium, cnt znuA and cnt ybtX mutants both had significant growth defects. Moreover, a znuA ybtX cnt mutant was completely attenuated for growth, which was rescued by zinc but not iron supplementation. While the cnt operon is present in Y. pestis, growth of analogous cnt mutants was not altered. Comparison of the cnt operons indicated the presence of two frameshift mutations in the predicted yersinopine importer cntQ in Y. pestis, suggesting that it is a pseudogene. Indeed, introduction of the same mutations into cntQ in Y. pseudotuberculosis znuA ybtX phenocopied a znuA ybtX cnt mutant. Finally, yersinopine also contributed to Y. pseudotuberculosis fitness in the presence of calprotectin and during infection in the murine model of yersiniosis. These data establish yersinopine as a primary zinc acquisition system in Y. pseudotuberculosis that is not required for Y. pestis to overcome zinc-mediated nutritional immunity and show divergent evolution in zinc acquisition strategies in these closely related species.

Zinc

metal homeostasis

nutritional immunity

Yersinia

metalloproteins

Details

Title: Subtitle: Yersinopine is a primary zinc acquisition system for Yersinia pseudotuberculosis
Creators: Mahendar Kadari - University of Louisville
Casey Weber - University of Louisville
Thomas E Kehl-Fie - University of Iowa
Robert D Perry - University of Kentucky
Juan C Ortiz-Marquez - Boston Children's Hospital
Oleg V Tsodikov - University of Kentucky
Sylvie Garneau-Tsodikova - University of Kentucky
Matthew B Lawrenz - University of Louisville
Resource Type: Journal article
Publication Details: mBio, e0200026
DOI: 10.1128/mbio.02000-26
PMID: 42752258
NLM abbreviation: mBio
ISSN: 2150-7511
eISSN: 2150-7511
Publisher: AMER SOC MICROBIOLOGY
Grant note: National Institute of Allergy and Infectious Diseases: R01AI148241 National Institute of General Medical Sciences: P20GM125504
The authors would like to thank Dr. Daniel Erickson for his assistance with animal experiments.
Language: English
Electronic publication date: 09/17/2026
Academic Unit: Microbiology and Immunology
Record Identifier: 9985231453702771

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