New findings on the interaction between RcsB and SlyA to control Salmonella Typhimurium virulence

MARIA FLORENCIA BALLESTEROS; JUAN VICENTE FARIZANO; MARÍA DE LAS MERCEDES PESCARETTI; MÓNICA A. DELGADO

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias 2017. LIII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB).; 2017

The Salmonella Typhimurium RcsCDB system regulates the synthesis of colanic acid and flagellum as well as the expression of numerous virulence genes. We previously demonstrated that the rcsC11 mutant, which constitutively activates the RcsB regulator, attenuates Salmonella virulence in an animal model. In addition, this attenuated phenotype could be also produced by deletion of the slyA gene. In this work we investigated if this antagonistic behavior is produced by the modulation of the expression of both regulator-encoding genes. We demonstrated that SlyA overproduction negatively regulates rcsB transcription. A bioinformatic analysis allowed us to identify a putative SlyA binding site on each of both promoters, PrcsDB and PrcsB, which control rcsB levels. In addition, we determined that SlyA is able to recognize and bind to these predicted sites to modulate the activity of both rcsB promoters. According to these results, SlyA represses rcsB transcription by direct binding to specific sites located on the rcsB promoters, thus accounting for the above antagonistic behavior. Moreover, we showed that the opposite effect between both regulators also physiologically affects the Salmonella motility phenotype. In this sense, we observed that under SlyA overproduction the PrcsB is repressed and consequently bacterial motility is increased. On the basis of these results, we suggest that during infection the different RcsB levels produced act as a switch between the Salmonella virulent or attenuated form. Thereby, we propose that higher concentrations of RcsB tilt the balance towards the attenuated form, while absence or low concentrations resulting from SlyA overproduction does it towards the virulent form.