Staphylococcus aureus can switch from a planktonic form of its lifestyle to other modes of existence that include biofilms1,2 and small colony variants (SCVs) 2,3 .These alternative lifestyles are rarely diagnosed or eradicated by usual antibiotic regimes and therefore become the basis for persistent and relapsing diseases 3,4. The bacterial stress response has been shown to be part of this lifestyle switching3. The oxidative stress 7 , nitrosative stress 5,7 and the formation of aldehydes 6 from several host cells and pathways are a main source of stress on invading bacteria and a key part of bacterial survival in different anatomical niches . In this study, we have examined the growth and response to (eight) known host generated chemical stresses involved in nitrosative, oxidative and aldehyde stresses encountered by pathogenic bacteria. We have studied a set of 63 clinical isolates of S. aureus isolated from the Women’s and Children’s Hospital (Adelaide) and also 8 reference strains. These represent isolates sourced from nosocomial and community-acquired infections and lung, skin and soft tissues isolates and blood isolates. Our results have shown that there are differences in the ability of these S. aureus isolates to grow and in particular, there are differences in stress response among these isolates. We have identified specific clinical isolates that responded exceptionally to stress, being highly resistant or inducing their biofilm formation or SCVs. This implied there are special pathways for stress response in these isolates and these are related to biofilm formation and SCVs. A key aim of our work is elucidating the molecular pathway/s unique to these isolates and the gene expression essential for this stress response and for biofilm or SCVs lifestyles.