Pan-genomic analysis of the species Salmonella enterica: Identification of core essential and putative essential genes

Background: Essential genes are defined as the minimal gene set required to support bacterial life. In order to develop new antimicrobials to treat multidrug-resistant pathogens, such as serovars of Salmonella enterica, the identification of essential genes is crucial. Methodology: In the present work, we hypothesize that essential genes within a group of evolutionary closely related organisms may be highly conserved. We, therefore, conducted an extensive comparative genomic analysis of 44 genome sequences representing 17 serovars of S. enterica to gain an improved understanding of conserved essential genes for its survival. Results: Pan-genome estimates indicate that the genus Salmonella displays an open pan-genome structure comprising a reservoir of 10,775 gene families. Of these, 2847, 4657, and 3271 constitute the core gene families (CGFs), dispensable gene families (DGFs), and strain-specific gene families (SSGFs), respectively. The pan-genome family tree based on the presence/absence of gene families is highly concordant with the 16S rRNA tree, though the former provides a more robust phylogenetic resolution. The Clusters of Orthologous Groups of proteins (COGs) database categorized the vast majority of the CGFs (40.9%) to metabolism, whereas a large proportion of the DGFs (70.6%) was uncharacterized. Homology analysis of the CGFs against the Database of essential genes (DEG) identified 1695 essential CGFs (E-CGFs). Of these, 687 are experimentally verified as essential in Salmonella, 1157 are identified in >= 2 species, 159 are conserved in >= 7 species, and 538 were present in at least one species. Thus, for the species, S. enterica 69%, 52%, and 31% of the genome are dedicated to the core, essential, and dispensable functions, respectively. Conclusion: The E-CGFs identified may serve as important targets for the development of novel antimicrobials, and their detailed analysis may shed new light on a better understanding of Salmonella's survival.