The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production in Klebsiella oxytoca
Klebsiella oxytoca 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...
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Multidisciplinary Digital Publishing Institute
2025
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| Online Access: | https://hdl.handle.net/1721.1/158154 |
| _version_ | 1824458092074500096 |
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| author | Varela-Nájera, Ramón G. De la Cruz, Miguel A. Soria-Bustos, Jorge González-Horta, Carmen Delgado-Gardea, Ma Carmen E. Yáñez-Santos, Jorge A. Cedillo, María L. Hirakawa, Hidetada Fox, James G. Sánchez-Ramírez, Blanca Ares, Miguel A. |
| author2 | Massachusetts Institute of Technology. Division of Comparative Medicine |
| author_facet | Massachusetts Institute of Technology. Division of Comparative Medicine Varela-Nájera, Ramón G. De la Cruz, Miguel A. Soria-Bustos, Jorge González-Horta, Carmen Delgado-Gardea, Ma Carmen E. Yáñez-Santos, Jorge A. Cedillo, María L. Hirakawa, Hidetada Fox, James G. Sánchez-Ramírez, Blanca Ares, Miguel A. |
| author_sort | Varela-Nájera, Ramón G. |
| collection | MIT |
| description | Klebsiella oxytoca 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 K. oxytoca. Our findings strongly indicate that OmpR is a repressor of the aroX and npsA genes, the first genes of aroX 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 K. oxytoca 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. |
| first_indexed | 2025-02-19T04:20:23Z |
| format | Article |
| id | mit-1721.1/158154 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2025-02-19T04:20:23Z |
| publishDate | 2025 |
| publisher | Multidisciplinary Digital Publishing Institute |
| record_format | dspace |
| spelling | mit-1721.1/1581542025-02-03T16:16:03Z The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production in Klebsiella oxytoca Varela-Nájera, Ramón G. De la Cruz, Miguel A. Soria-Bustos, Jorge González-Horta, Carmen Delgado-Gardea, Ma Carmen E. Yáñez-Santos, Jorge A. Cedillo, María L. Hirakawa, Hidetada Fox, James G. Sánchez-Ramírez, Blanca Ares, Miguel A. Massachusetts Institute of Technology. Division of Comparative Medicine Klebsiella oxytoca 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 K. oxytoca. Our findings strongly indicate that OmpR is a repressor of the aroX and npsA genes, the first genes of aroX 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 K. oxytoca 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. 2025-02-03T16:16:02Z 2025-02-03T16:16:02Z 2025-01-14 2025-01-24T13:16:15Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/158154 Varela-Nájera, R.G.; De la Cruz, M.A.; Soria-Bustos, J.; González-Horta, C.; Delgado-Gardea, M.C.E.; Yáñez-Santos, J.A.; Cedillo, M.L.; Hirakawa, H.; Fox, J.G.; Sánchez-Ramírez, B.; et al. The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production in Klebsiella oxytoca. Microorganisms 2025, 13, 158. PUBLISHER_CC http://dx.doi.org/10.3390/microorganisms13010158 Microorganisms Creative Commons Attribution https://creativecommons.org/licenses/by/4.0/ application/pdf Multidisciplinary Digital Publishing Institute Multidisciplinary Digital Publishing Institute |
| spellingShingle | Varela-Nájera, Ramón G. De la Cruz, Miguel A. Soria-Bustos, Jorge González-Horta, Carmen Delgado-Gardea, Ma Carmen E. Yáñez-Santos, Jorge A. Cedillo, María L. Hirakawa, Hidetada Fox, James G. Sánchez-Ramírez, Blanca Ares, Miguel A. The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production in Klebsiella oxytoca |
| title | The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production in Klebsiella oxytoca |
| title_full | The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production in Klebsiella oxytoca |
| title_fullStr | The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production in Klebsiella oxytoca |
| title_full_unstemmed | The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production in Klebsiella oxytoca |
| title_short | The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production in Klebsiella oxytoca |
| title_sort | response regulator ompr negatively controls the expression of genes implicated in tilimycin and tilivalline cytotoxin production in klebsiella oxytoca |
| url | https://hdl.handle.net/1721.1/158154 |
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