Urogenital infections select for reduced ability to grow in a low-iron environment and reduced blood survival for Staphylococcus aureus

Immunity through nutrient sequestration is one of the means by which a host can protect itself from infection. As a consequence, many micro-organisms have evolved strategies to overcome this, including the opportunistic pathogen Staphylococcus aureus . In this study, we focussed on a population of SAB isolates with the aim of better understanding their ability to grow in a low-iron environment and observed a significant association between a weakened ability to grow in a low-iron environment and whether the entry point of the bacteria into the bloodstream was urogenital in origin. Follow-up experiments demonstrated that urine at 10% provided sufficient iron for both a defined iron uptake mutant ( sbnE:: Tn) and our iron-dependent clinical isolates to grow, in the absence of other sources of iron. This potentially explains their association with this environment where, although at relatively low levels, the iron there is such that those with poor iron utilization ability can survive. This does not however explain how these isolates went on to successfully cause bacteraemia, given how poorly available iron is in the bloodstream. To determine whether these iron-dependent isolates had some alternative means of surviving in blood, we exposed them to fresh human blood and found that although they had previously all successfully established an infection in the bloodstream, the iron-dependent isolates did not survive as well as the non-dependent isolates. This work highlights the complexity and apparent contradictory nature of the factors that contribute to the development of this important disease.