The OxyR-Responsive TacAT Module Promotes Oxidative Stress Adaptation and In Vivo Fitness in K. pneumoniae
- 1West China Hospital of Sichuan University
Abstract
During infection, Klebsiella pneumoniae must withstand host-derived oxidative stress not only by detoxifying reactive oxygen species (ROS) but also by repairing oxidative damage to cellular physiology. How these detoxification and stress-adaptive responses are coordinated remains unclear. Here, we identify a plasmid-encoded tacAT locus as an OxyR-responsive regulatory module that supports peroxide tolerance and in vivo fitness in K. pneumoniae. Guided by the conservation of the OxyR DNA-binding domain and its consensus binding motif, we surveyed promoter-proximal regions of the K. pneumoniae CRK3022 chromosome and plasmids for candidate OxyR-responsive loci. This analysis identified tacAT, a putative type II toxin-antitoxin (TA) module, as the only plasmid-associated candidate. OxyR directly bound the tacAT promoter and contributed to tacAT induction during hydrogen peroxide (H?O?) stress. The TacAT complex exhibited DNA-binding and transcriptional regulatory activity, promoting the expression of genes linked to protein quality control and membrane/envelope homeostasis, including clpB, htpG, cadC, bhsA, and marA. Deletion of tacAT compromised survival under lethal peroxide challenge and attenuated bacterial dissemination, tissue pathology, and inflammatory responses in a murine bacteremia model. These findings define an OxyR-TacAT regulatory branch that connects peroxide sensing with stress-adaptive gene expression, revealing how a TA-associated module can be integrated into stress-adaptive programs during host-associated oxidative stress.
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BibTeX
@misc{zhou2026oxyrresponsive,
title = {{The OxyR-Responsive TacAT Module Promotes Oxidative Stress Adaptation and In Vivo Fitness in K. pneumoniae}},
author = {J. Zhou and H. Ma and Z. Sha and S. Liu and J. Rao and N. Zhao and X. Mou and C. Chen and H. Li and H. Liu and H. Wu and R. Bao},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.23.753711},
url = {https://www.biorxiv.org/content/10.64898/2026.09.23.753711v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - The OxyR-Responsive TacAT Module Promotes Oxidative Stress Adaptation and In Vivo Fitness in K. pneumoniae
AU - J. Zhou
AU - H. Ma
AU - Z. Sha
AU - S. Liu
AU - J. Rao
AU - N. Zhao
AU - X. Mou
AU - C. Chen
AU - H. Li
AU - H. Liu
AU - H. Wu
AU - R. Bao
PY - 2026
DA - 2026/09/23
PB - bioRxiv
DO - 10.64898/2026.09.23.753711
UR - https://www.biorxiv.org/content/10.64898/2026.09.23.753711v1
AB - During infection, Klebsiella pneumoniae must withstand host-derived oxidative stress not only by detoxifying reactive oxygen species (ROS) but also by repairing oxidative damage to cellular physiology. How these detoxification and stress-adaptive responses are coordinated remains unclear. Here, we identify a plasmid-encoded tacAT locus as an OxyR-responsive regulatory module that supports peroxide tolerance and in vivo fitness in K. pneumoniae. Guided by the conservation of the OxyR DNA-binding domain and its consensus binding motif, we surveyed promoter-proximal regions of the K. pneumoniae CRK3022 chromosome and plasmids for candidate OxyR-responsive loci. This analysis identified tacAT, a putative type II toxin-antitoxin (TA) module, as the only plasmid-associated candidate. OxyR directly bound the tacAT promoter and contributed to tacAT induction during hydrogen peroxide (H?O?) stress. The TacAT complex exhibited DNA-binding and transcriptional regulatory activity, promoting the expression of genes linked to protein quality control and membrane/envelope homeostasis, including clpB, htpG, cadC, bhsA, and marA. Deletion of tacAT compromised survival under lethal peroxide challenge and attenuated bacterial dissemination, tissue pathology, and inflammatory responses in a murine bacteremia model. These findings define an OxyR-TacAT regulatory branch that connects peroxide sensing with stress-adaptive gene expression, revealing how a TA-associated module can be integrated into stress-adaptive programs during host-associated oxidative stress.
ER -