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bioRxiv · 10.64898/2026.09.23.753711

The OxyR-Responsive TacAT Module Promotes Oxidative Stress Adaptation and In Vivo Fitness in K. pneumoniae

Zhou, J.·Ma, H.·Sha, Z.·Liu, S.·Rao, J.·Zhao, N.·Mou, X.·Chen, C.·Li, H.·Liu, H.·Wu, H.·Bao, R.
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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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Zhou, J., Ma, H., Sha, Z., Liu, S., Rao, J., Zhao, N., Mou, X., Chen, C., Li, H., Liu, H., Wu, H., Bao, R.. 2026-09-24. The OxyR-Responsive TacAT Module Promotes Oxidative Stress Adaptation and In Vivo Fitness in K. pneumoniae. https://doi.org/10.64898/2026.09.23.753711

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