Fuente: Microorganisms - Revista científica (MDPI) Microorganisms, Vol. 14, Pages 1144: The Quorum-Sensing Regulator SdiA Activates npsA Expression and Modulates Cytotoxicity in Klebsiella oxytoca
Microorganisms doi: 10.3390/microorganisms14051144
Authors:
Carlos J. Jiménez-Sánchez
Cristopher Perez
Sandra Rivera-Gutiérrez
Jorge Soria-Bustos
Fernando Chimal-Cázares
Roberto Rosales-Reyes
Santa Mejía-Ventura
Gabriela Hernández-Martínez
Miguel A. De la Cruz
Jorge A. Yañez-Santos
Maria L. Cedillo
James G. Fox
Miguel A. Ares

Toxigenic Klebsiella oxytoca strains linked to antibiotic-associated hemorrhagic colitis produce the cytotoxins tilimycin and tilivalline, which contribute to intestinal epithelial damage during infection. Tilimycin and tilivalline are synthesized by enzymes encoded within the nonribosomal peptide synthetase (NRPS) operon, yet the regulatory mechanisms controlling operon expression remain poorly understood. SdiA, an orphan LuxR-type quorum-sensing regulator, detects exogenous N-acyl homoserine lactones (AHLs) produced by neighboring bacterial species and modulates gene expression in response to interspecies communication. Although SdiA has been implicated in virulence regulation in several enteric pathogens, its role in K. oxytoca remains unclear. This study demonstrates that SdiA positively regulates npsA, the first gene in the NRPS operon, and that this regulatory effect is enhanced in the presence of exogenous AHL. Electrophoretic mobility shift assays indicate that SdiA directly binds to the upstream regulatory region of npsA, supporting a direct interaction consistent with positive transcriptional regulation. Furthermore, deletion of sdiA significantly reduces cytotoxicity toward HeLa cells under the conditions tested. Collectively, these findings identify SdiA as a quorum-sensing-responsive activator of npsA expression and support its role in modulating cytotoxicity in toxigenic K. oxytoca strains. These results provide new insight into the influence of interspecies quorum-sensing signals on virulence-associated regulatory pathways in K. oxytoca.