We identified the two second messengers c-di-GMP and cAMP as being involved in ExlA regulation. We demonstrated that, as observed with T3SS, the CyaB-cAMP/Vfr pathway controls positively
exlBA pointing out the similarities in the mechanism of regulation of the two main virulence factors of
P. aeruginosa [14]. To explain the low expression levels of
exlBA, a transposon mutant library was created in a strain carrying
in situ transcriptional
exlBA::lacZ fusion. This genome-wide screening identified a new regulator that we named ErfA (ExlA Regulatory Factor A), belonging to the family of Xenobiotic Response Element (XRE)-like transcription factor. We confirmed that its inactivation strongly increased the mutant cytotoxicity towards epithelial cells and virulence in a
Galleria model of infection. The erfA gene is conserved in different
Pseudomonas sp, even those without the
exlBA operon. Genome wide approaches (RNAseq and ChIPseq) demonstrated that ErfA controls also an operon of two genes of unknown function,
ergAB (ErfA Regulated Genes A and B). Phenotypic screens and metabolomics are underway to identify the exact metabolic pathway(s) in play with ErfA/ExlA.
[15]
Trouillon
et al (2020)
Nucleic Acids Res.
References
[14] Berry
et al (2018)
Journal of bacteriology 200(12).
[15] Trouillon
et al (2020)
Nucleic Acids Res. pii: gkz1232. doi: 10.1093/nar/gkz1232