RfaH is essential for virulence and adaptive responses in Yersinia pseudotuberculosis infection
Author(s)
Waititu, Joram Kiriga
Nilsson, Kristina
Larrouy-Maumus, Gerald
Costa, Tiago RD
Avican, Kemal
Type
Journal Article
Abstract
We previously suggested that increased expression of the gene encoding transcriptional antiterminator RfaH during Yersinia pseudotuberculosis transcriptional reprogramming is necessary for adapting to persistent infection. In this study, we examined the role of RfaH in virulence and bacterial physiology under infection-relevant stress conditions, and identified genes differentially regulated in the absence of RfaH in Y. pseudotuberculosis. We employed a mouse infection model and phenotypic assays to test RfaH’s role in virulence and physiology, as well as RNA sequencing, including O-antigen biosynthesis-deficient strains. Our findings demonstrate that loss of RfaH significantly attenuates virulence, reducing the capacity of Y. pseudotuberculosis to establish persistent infection. RfaH expression is increased during the stationary growth phase and under various stress conditions, such as high osmolarity and bile salts, which are known to induce envelope stress. Functional assays revealed that the ΔrfaH strain displayed defects in motility and increased clumping, indicating altered surface properties affecting motility. Moreover, transcriptomic profiling of the ΔrfaH strain revealed a specific RfaH-dependent gene set after filtering out genes affected by O-antigen-related mutations, thereby minimizing confounding effects from surface structure alterations. These results suggest that RfaH influences a broader set of virulence and adaptation pathways beyond O-antigen regulation. Collectively, our findings suggest that RfaH is essential for the virulence and adaptive capacity of Y. pseudotuberculosis to colonize the host. This study provides insights into regulatory mechanisms that facilitate bacterial survival in hostile environments and highlights the importance of RfaH and its regulatory targets in the pathogenesis of Y. pseudotuberculosis.
Editor(s)
Chang, Yung-Fu
Date Issued
2025-11-01
Date Acceptance
2025-09-09
Citation
mBio, 2025, 16 (11), pp.1-22
ISSN
2161-2129
Publisher
American Society for Microbiology
Start Page
1
End Page
22
Journal / Book Title
mBio
Volume
16
Issue
11
Copyright Statement
© 2025 Waititu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41020597
Subjects
RNA-seq
RfaH
Yersinia
cell surface
infection
Publication Status
Published
Coverage Spatial
United States
Article Number
e02122-25
Date Publish Online
2025-09-29