The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production in <i>Klebsiella oxytoca</i>

The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production in <i>Klebsiella oxytoca</i>

<i>Klebsiella oxytoca</i> toxigenic strains represent a critical health threat, mainly due to their link to antibiotic-associated hemorrhagic colitis. This serious condition results from the bacteria’s ability to produce tilimycin and tilivalline cytotoxins. Our research highlights the p...

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Main Authors: Ramón G. Varela-Nájera, Miguel A. De la Cruz, Jorge Soria-Bustos, Carmen González-Horta, Ma Carmen E. Delgado-Gardea, Jorge A. Yáñez-Santos, María L. Cedillo, Hidetada Hirakawa, James G. Fox, Blanca Sánchez-Ramírez, Miguel A. Ares
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Microorganisms
Subjects:
<i>Klebsiella oxytoca</i>
OmpR
<i>aroX</i>
<i>npsA</i>
tilimycin
tilivalline
Online Access:https://www.mdpi.com/2076-2607/13/1/158
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Summary:<i>Klebsiella oxytoca</i> toxigenic strains represent a critical health threat, mainly due to their link to antibiotic-associated hemorrhagic colitis. This serious condition results from the bacteria’s ability to produce tilimycin and tilivalline cytotoxins. Our research highlights the pivotal role of OmpR, a key regulator within the EnvZ/OmpR two-component system, in controlling the virulence factors associated with <i>K. oxytoca</i>. Our findings strongly indicate that OmpR is a repressor of the <i>aroX</i> and <i>npsA</i> genes, the first genes of <i>aroX</i> and NRPS operons, respectively, which are indispensable for producing these enterotoxins. Notably, in the absence of OmpR, we observe a significant increase in cytotoxic effects on Caco-2 cells. These observations identify OmpR as a crucial negative transcription regulator for both operons, effectively managing the release of these cytotoxins. This research deepens our understanding of the mechanisms of toxigenic <i>K. oxytoca</i> and opens promising avenues for targeting OmpR for new therapeutic interventions. By focusing on this innovative approach, we can develop more effective solutions to combat this pressing health challenge, ultimately improving patient outcomes against this pathogen.
ISSN:2076-2607

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