Salmonella enterica Serovars Dublin and Enteritidis Comparative Proteomics Reveals Differential Expression of Proteins Involved in Stress Resistance, Virulence, and Anaerobic Metabolism

Abstract
The Enteritidis and Dublin serovars of Salmonella enterica are phylogenetically closely related yet they differ significantly in host-range and virulence. S. Enteritidis is a broad-host range serovar that commonly causes self-limited gastroenteritis in humans, whereas S. Dublin is a cattle-adapted serovar that can infect humans often resulting in invasive extra-intestinal disease. The mechanism underlying the higher invasiveness of S. Dublin remains undetermined. In this work, we quantitatively compared the proteomes of clinical isolates of each serovar grown under gut mimicking conditions. Compared to S. Enteritidis, the S. Dublin proteome was enriched in proteins linked to response to several stress conditions, such as those encountered during host infection, as well as to virulence. The S. Enteritidis proteome contained several proteins related to central anaerobic metabolism pathways that were undetected in S. Dublin. In contrast to what has been observed in other extra-intestinal serovars, most of the coding genes for these pathways are not degraded in S. Dublin. Thus, we provide evidence that S. Dublin may have much more affected metabolic functions than previously reported based on genomic studies. Single and double null mutants in stress response proteins Dps, YciF and YgaU demonstrate their relevance to S. Dublin invasiveness in a murine model of invasive salmonellosis. All in all, this work provides a basis for understanding inter-serovar differences in invasiveness and niche adaptation, underscoring the relevance of using proteomic approaches to complement genomic studies.
Funding Information
  • Agencia Nacional de Investigación e Innovación (PhD Fellowship)
  • Agencia Nacional de Investigación e Innovación (PostDoc Fellowship)
  • Agencia Nacional de Investigación e Innovación (Masters Fellowship)
  • UdelaR | Comisión Sectorial de Investigación Científica (Grupos I+D)
  • UdelaR | Comisión Sectorial de Investigación Científica (Grupos I+D)