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Deciphering regulatory network controlling the expression of Exolysin A

Published on 19 February 2020
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