SdiA, a Quorum Sensing Transcriptional Regulator, Enhanced the Drug Resistance of Cronobacter sakazakiiand Suppressed its Motility, Adhesion and Biofilm Formation

Abstract

Cronobacter sakazakii is a common foodborne pathogen, and the mortality rate of its infection is as high as 40-80%. Quorum sensing is a regulation system of bacterial density-dependent multigene expression and is an important regulatory mechanism involved in adhesion, biofilm formation and virulence. C. sakazakii contains a QS signal molecular receiver, which is the LuxR receptor homolog SdiA, but its regulatory mechanism in C. sakazakii QS has not been defined. Here, we further determined the effect of SdiA on the QS system of C. sakazakii. The SdiA gene in C. sakazakii was knocked out by gene editing technology, and the biological characteristics of the {Delta}sdiA gene deletion strain of C. sakazakii were studied, followed by transcriptome analysis to elucidate its effects. The results suggested that SdiA enhanced the drug resistance of C. sakazakii but diminished its motility, adhesion and biofilm formation ability and had no effect on its growth. Transcriptome analysis showed that the deletion of the SdiA gene upregulated the expression levels of D-galactose operon genes (including dgoR, dgoK, dgoA, dgoD and dgoT) and flagella-related genes (FliA and FliC) in C. sakazakii and downregulated the expression levels of related genes in the type VI secretion system (VasK gene was downregulated by 1.53-fold) and ABC transport system (downregulated by 1.5-fold), indicating that SdiA was related to the physiological metabolism of C. sakazakii. The results of this study may be useful for clarifying the pathogenic mechanism of C. sakazakii and provide a theoretical basis for controlling bacterial infection. IMPORTANCECronobacter sakazakii, as an emerging opportunistic foodborne pathogen, was associated with sepsis, meningitis and necrotizing enterocolitis in neonates and infants, with a mortality rate of 40-80%. Quorum sensing plays an important regulatory role in the pathogenicity of C. sakazakii. Nevertheless, the regulatory mechanism of QS in C. sakazakii remains unknown. Here, we studied the QS transcriptional regulator SdiA of C. sakazakii. We revealed the regulatory mechanisms of SdiA in C. sakazakii cell adhesion, motility, biofilm formation and drug resistance. It was helpful to further explore the function of the SdiA gene, revealing the pathogenic mechanism of C. sakazakii. It will also provide a new target for therapeutic interventions targeting the pathogenicity of C. sakazakii and developing quorum-sensing inhibitors.