Switching apo- and holo-IscR control of LcrF alters how iron and oxygen regulate Yersinia virulence factors.

Authors

Mané Ohanyan, George Imre Balazs, Karthik Hullahalli, Diana Fernandez Pacheco, Caia Lomeli, Katherine G Dailey, Erin Mettert, Diana Hooker-Romero, Leah Schwiesow, Patricia J Kiley, Matthew K Waldor, Victoria Auerbuch

Published in

Infection and immunity. Pages e0035826. Sep 15, 2026. Epub Sep 15, 2026.

Abstract

Iron and oxygen availability fluctuate spatially across mammalian tissues as well as temporally during bacterial infection. The [2Fe-2S] cluster-coordinating transcription factor IscR senses changes in iron and oxygen levels and plays a pivotal role in how Yersinia, Salmonella, and Vibrio regulate critical virulence genes, like the type III secretion system (T3SS). We previously showed that clusterless apo-IscR promotes expression of the Yersinia pseudotuberculosis T3SS master regulator LcrF by binding a type 2 IscR-binding motif in the lcrF promoter, thereby facilitating T3SS expression and disseminated infection. Here, we sought to address how IscR ligation of its [2Fe-2S] cluster impacts LcrF expression and bacterial virulence. We engineered a Y. pseudotuberculosis mutant strain with its native type 2 IscR-binding motif swapped with a type 1 motif that binds [2Fe-2S]-IscR but not apo-IscR. This lcrF^pType1 mutant hyperexpressed LcrF and T3SS-associated proteins in iron-replete anaerobic conditions that favor [2Fe-2S]-IscR. To understand the consequence of this dysregulated expression, we used barcoded Y. pseudotuberculosis libraries to probe infection dynamics of the WT and lcrF ^pType1 mutant strains following oral infection of mice. The lcrF^pType1 mutant experienced altered colonization bottleneck and dissemination patterns compared to WT Yersinia, suggesting that expressing LcrF and T3SS genes in response to [2Fe-2S]-IscR rather than apo-IscR may alter infection dynamics.

PMID:
42742341
Bibliographic data and abstract were imported from PubMed on 15 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.