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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2025-01-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Ramón G. Varela-Nájera |
| collection | DOAJ |
| description | <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. |
| format | Article |
| id | doaj-art-8ddd48fbee4146918ed3ea40588b1857 |
| institution | Kabale University |
| issn | 2076-2607 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj-art-8ddd48fbee4146918ed3ea40588b18572025-01-24T13:42:51ZengMDPI AGMicroorganisms2076-26072025-01-0113115810.3390/microorganisms13010158The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production in <i>Klebsiella oxytoca</i>Ramón G. Varela-Nájera0Miguel A. De la Cruz1Jorge Soria-Bustos2Carmen González-Horta3Ma Carmen E. Delgado-Gardea4Jorge A. Yáñez-Santos5María L. Cedillo6Hidetada Hirakawa7James G. Fox8Blanca Sánchez-Ramírez9Miguel A. Ares10Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, MexicoCentro de detección Biomolecular, Benemérita Universidad Autónoma de Puebla, Puebla 72592, MexicoCentro de detección Biomolecular, Benemérita Universidad Autónoma de Puebla, Puebla 72592, MexicoFacultad de Ciencias Químicas, Universidad Autónoma de Chihuahua, Circuito Universitario Campus II, Chihuahua 31125, MexicoFacultad de Ciencias Químicas, Universidad Autónoma de Chihuahua, Circuito Universitario Campus II, Chihuahua 31125, MexicoCentro de detección Biomolecular, Benemérita Universidad Autónoma de Puebla, Puebla 72592, MexicoCentro de detección Biomolecular, Benemérita Universidad Autónoma de Puebla, Puebla 72592, MexicoDepartment of Bacteriology, Graduate School of Medicine, Gunma University, Maebashi 371-8514, JapanDivision of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USAFacultad de Ciencias Químicas, Universidad Autónoma de Chihuahua, Circuito Universitario Campus II, Chihuahua 31125, MexicoUnidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico<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.https://www.mdpi.com/2076-2607/13/1/158<i>Klebsiella oxytoca</i>OmpR<i>aroX</i><i>npsA</i>tilimycintilivalline |
| spellingShingle | 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 The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production in <i>Klebsiella oxytoca</i> Microorganisms <i>Klebsiella oxytoca</i> OmpR <i>aroX</i> <i>npsA</i> tilimycin tilivalline |
| title | The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production in <i>Klebsiella oxytoca</i> |
| title_full | The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production in <i>Klebsiella oxytoca</i> |
| title_fullStr | The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production in <i>Klebsiella oxytoca</i> |
| title_full_unstemmed | The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production in <i>Klebsiella oxytoca</i> |
| title_short | The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production in <i>Klebsiella oxytoca</i> |
| title_sort | response regulator ompr negatively controls the expression of genes implicated in tilimycin and tilivalline cytotoxin production in i klebsiella oxytoca i |
| topic | <i>Klebsiella oxytoca</i> OmpR <i>aroX</i> <i>npsA</i> tilimycin tilivalline |
| url | https://www.mdpi.com/2076-2607/13/1/158 |
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