Role of a single non-synonymous SNP in HilD in the virulence phenotype of isolates from a Salmonella Derby specific Pulsed Field Gel Electrophoresis profile (PFGE), SXB_BS.0204, exhibiting a marked adaptation to swine.

Salmonella enterica includes serovars and intraserovar variants with distinctive host ranges. Some genetic signatures have already been observed in variants with distinct host tropism, but the molecular mechanisms of host adaption remain largely unrevealed. Salmonella enterica serovar Derby is mainly associated to swine, but still ranked among the more isolated serovars from humans. Here, we identified a S. Derby Pulsed Field Gel Electrophoresis profile (PFGE), SXB_BS.0204, exhibiting a marked adaptation to swine, as its prevalence in humans is ~10 times lower compared to the other S. Derby PFGE profiles. The invasion and replication rates of SXB_BS.0204 isolates in human cells were up to 4 logs lower than those of isolates from closely related PFGE profiles, whereas in swine cells differences were significantly reduced to just one log. One single non-synonymous point mutation in HilD, the master-regulator of the Salmonella Pathogenicity Island 1 (SPI-1) was found to be distinctive of SXB_BS.0204 isolates. We demonstrated that this mutation, responsible for the SXB_BS.0204 attenuated virulence phenotype, cause a total loss of function of the SPI-1 regulator. Altogether, our data suggest how host adaptation could depend by the HilD functionality, that differently condition the virulence phenotype in distinct host cells.