The changes metabolic profiles observed in this study could indicate the existence of a phenotypic shift that can occur within a mixture of populations (Alreshidi et al., 2013). The phenotypic shifts in bacterial cells and colonies such as SCVs has been previously demonstrated following exposure to various environmental parameters including osmotic and cold stresses (Onyango et al., 2012, 2013; Crompton et al., 2014). Earlier studies have shown that SCVs have slower generation times, reduced release of virulence factors and are found to be auxotrophic for hemin and menadione compounds (Von Eiff, 2008; Proctor et al., 2014; Bui et al., 2015). Thus, it has been suggested, that bacterial cells persistently detect and respond to stress conditions by establishing the most effective and efficient phenotypes for survival. SCVs are highly associated with biofilm formation. These two lifestyles of S. aureus represent a very robust protective and adaptive mechanism in response to environmental threats. Metabolic studies have demonstrated a strong relationship between biofilm formation and metabolite changes. For example, it has been indicated that polysaccharide intercellular adhesin (PIA) production in biofilm is regulated by tricarboxylic acid cycle components (Sadykov et al., 2010) and the osmotic stress stimulates biofilm formation (Knobloch et al., 2001; Oniciuc et al., 2016). Several metabolites associated with purine and pyrimidine catabolism were reported to significantly contribute to distinguishing between planktonic and biofilm cells (Liebeke et al., 2011; Ammons et al., 2014). It has also been shown that the uptake of purine bases were highly necessary for biofilm formation (Zhu et al., 2007). This may explain the significant up-regulation of purine and pyrimidine nucleotides under conditions of osmotic stress in this study.