The MarR-family regulator TilR links biosynthesis of enterotoxin tilimycin with physiologic adaptation in Klebsiella oxytoca
- 1UConn Health
Abstract
Members of the Klebsiella oxytoca species complex (KoSC) are ubiquitous gut colonizers that produce the DNA-damaging enterotoxin tilimycin (TM) as part of their virulence-related program. A MarR-like transcriptional regulator, herein designated TilR, controls expression of the divergently transcribed aroX- and NRPS-operons responsible for TM production. Deletion of tilR resulted in pronounced induction of both operons, elevated toxin production, and increased cytotoxicity - establishing TilR as the key repressor of TM biosynthesis. TilR is encoded downstream of the NRPS operon and binds a 20 bp motif within the aroX-NRPS intergenic region, spatially separated from the predicted promoters driving toxin gene expression. Analysis of global transcriptome profiles revealed that TilR, the most highly expressed of the seven MarRs in KoSC, links toxin biosynthesis to a broader transcriptional network involved in nutrient acquisition, stress adaptation, and central metabolism. In addition, TM production coincided with induction of multiple virulence-associated genes involved in adhesion, biofilm formation, and iron acquisition. Phylogenetic and structural analyses revealed that TilR is distinct from canonical MarRs and absent from members of the closely related, competing Klebsiella pneumoniae species complex (KpSC). These findings identify TilR as an evolutionarily specialized global regulator that coordinates TM biosynthesis with broader metabolic, stress-adaptive, and virulence-associated transcriptional responses.
Related
- Genomics of the Genus Rhodiola: From Genome Assembly to High-Altitude Adaptation and Bioactive Compound Biosynthesis
- Anthocyanins in woody ornamental plants: biosynthesis, regulatory networks, and trade-offs in stress adaptation
- Single‐Cell Transcriptomics and Metabolomics Reveal Glutamate Dehydrogenase as a Central Regulator of Nitrogen Metabolic Remodeling During Alkalinity Adaptation in Crustaceans
- Combined production of Non-Hemolytic Enterotoxin and Sphingomyelinase as a marker of diarrheal food poisoning strains in the Bacillus cereus group
- Glucocorticoids in breast cancer: physiologic mechanisms and relationship to risk, survival, and treatment response.
BibTeX
@misc{unterhauser2026marrfamily,
title = {{The MarR-family regulator TilR links biosynthesis of enterotoxin tilimycin with physiologic adaptation in Klebsiella oxytoca}},
author = {K. Unterhauser and A. A. Grassmann and P. Balachandran and A. A. Provatas and Y. Zhou and M. J. Caimano and J. D. Radolf and A. P. Matson},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.06.765007},
url = {https://www.biorxiv.org/content/10.64898/2026.11.06.765007v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - The MarR-family regulator TilR links biosynthesis of enterotoxin tilimycin with physiologic adaptation in Klebsiella oxytoca
AU - K. Unterhauser
AU - A. A. Grassmann
AU - P. Balachandran
AU - A. A. Provatas
AU - Y. Zhou
AU - M. J. Caimano
AU - J. D. Radolf
AU - A. P. Matson
PY - 2026
DA - 2026/11/06
PB - bioRxiv
DO - 10.64898/2026.11.06.765007
UR - https://www.biorxiv.org/content/10.64898/2026.11.06.765007v1
AB - Members of the Klebsiella oxytoca species complex (KoSC) are ubiquitous gut colonizers that produce the DNA-damaging enterotoxin tilimycin (TM) as part of their virulence-related program. A MarR-like transcriptional regulator, herein designated TilR, controls expression of the divergently transcribed aroX- and NRPS-operons responsible for TM production. Deletion of tilR resulted in pronounced induction of both operons, elevated toxin production, and increased cytotoxicity - establishing TilR as the key repressor of TM biosynthesis. TilR is encoded downstream of the NRPS operon and binds a 20 bp motif within the aroX-NRPS intergenic region, spatially separated from the predicted promoters driving toxin gene expression. Analysis of global transcriptome profiles revealed that TilR, the most highly expressed of the seven MarRs in KoSC, links toxin biosynthesis to a broader transcriptional network involved in nutrient acquisition, stress adaptation, and central metabolism. In addition, TM production coincided with induction of multiple virulence-associated genes involved in adhesion, biofilm formation, and iron acquisition. Phylogenetic and structural analyses revealed that TilR is distinct from canonical MarRs and absent from members of the closely related, competing Klebsiella pneumoniae species complex (KpSC). These findings identify TilR as an evolutionarily specialized global regulator that coordinates TM biosynthesis with broader metabolic, stress-adaptive, and virulence-associated transcriptional responses.
ER -