<i>Salmonella</i> pathogenicity Island 1 undergoes decay in serovars adapted to swine and poultry

Human salmonellosis is a high-priority foodborne disease worldwide. The main reservoir of <i>Salmonella</i> is livestock, mainly swine and poultry that are infected both by generalist serovars and serovars adapted to them. The most widespread livestock-adapted serovars are attenuated in both their primary hosts and humans. We previously identified a lineage of the swine-adapted <i>Salmonella</i> Derby carrying mutations in <i>Salmonella</i> Pathogenicity Island-1(SPI-1) giving attenuation. To evaluate if SPI-1 decay is a general feature of swine-adapted serovars, we analyzed the Enterobase global population of <i>Salmonella</i> serovars most frequently isolated from swine. We found that deleterious mutations in SPI-1 are accumulated more in swine-adapted (<i>S</i>. Derby and <i>Salmonella</i> Rissen) than in generalist (<i>Salmonella</i> Typhimurium, I 1,4,[5],12:i:-, and <i>Salmonella</i> Infantis) serovars. The genomes carrying such mutations are widespread in the population of <i>S</i>. Derby and <i>S</i>. Rissen, indicating that the occurrence and fixation of deleterious mutations in SPI-1 are frequent. Similarly, also poultry-adapted <i>Salmonella</i> Kentucky has accumulated deleterious mutations in SPI-1, leading to over 70% of mutated genomes of this serovar compared with negligible proportions of mutated genomes in the generalist serovars from poultry. Although <i>in vitro</i> attenuation of <i>S</i>. Derby carrying mutated SPI-1 had been previously demonstrated, we showed the same phenotype for mutated <i>S</i>. Rissen. Considering also the known attenuation of <i>S</i>. Kentucky, our population-scale findings provide evidence of progressive evolution toward the attenuation of serovars adapted to the main animal reservoirs of human salmonellosis through the food chain. Intensive farming with a high density of animals could be a possible driver of this evolution.IMPORTANCEThis study shows at the global population level of <i>Salmonella</i> that the main attenuated serovars adapted to food-producing animals are undergoing convergent evolution toward further attenuation through the decay of SPI-1, considered critically important for the intestinal phase of <i>Salmonella</i> infection. The drivers of this evolution are unknown, but they could be attributed, at least in part, to the intensive farming of livestock with its high densities. On one side, our results contribute to the knowledge of the interaction between livestock populations and their host-adapted serovars of <i>Salmonella</i>. On the other side, the study provides scientific background for reconsidering the microbiological criteria adopted by the food safety legislation of many countries that ask for the absence of <i>Salmonella</i> in foods, regardless of any virulence evaluation of the detected strain. In this respect, the study provides molecular bases to investigate the virulence of different lineages within these host-adapted serovars.