Phenotype and multi-omics comparison of Staphylococcus and Streptococcus uncovers pathogenic traits and predicts zoonotic potential

Abstract Background Staphylococcus and Streptococcus species can cause many different diseases, ranging from mild skin infections to life-threatening necrotizing fasciitis. Both genera consist of commensal species that colonize the skin and nose of humans and animals, and of which some can display a pathogenic phenotype. Results We compared 235 Staphylococcus and 315 Streptococcus genomes based on their protein domain content. We show the relationships between protein persistence and essentiality by integrating essentiality predictions from two metabolic models and essentiality measurements from six large-scale transposon mutagenesis experiments. We identified clusters of strains within species based on proteins associated to similar biological processes. We built Random Forest classifiers that predicted the zoonotic potential. Furthermore, we identified shared attributes between of Staphylococcus aureus and Streptococcus pyogenes that allow them to cause necrotizing fasciitis. Conclusions Differences observed in clustering of strains based on functional groups of proteins correlate with phenotypes such as host tropism, capability to infect multiple hosts and drug resistance. Our method provides a solid basis towards large-scale prediction of phenotypes based on genomic information.