Almost 50 years ago, carbon dioxide (CO2) dependent variants were described in non-autotrophic bacteria. However, the underlying mechanism of CO2-dependency are not clear. In this study, we demonstrate that the Staphylococcus aureus mpsAB operon does not only contribute to the production of membrane potential but is also vital for growth under atmospheric CO2 concentration. Deletion mutants of mpsA, mpsB, and mpsABC hardly grew under atmospheric air conditions but could be restored to near wild-type levels under elevated CO2 or bicarbonate concentrations. Uptake studies with radiolabeled sodium bicarbonate (NaH14CO3) revealed that MpsAB represents a bicarbonate/dissolved inorganic carbon (DIC) transporter. Additionally, an Escherichia coli carbonic anhydrase (CA) can mutant which is unable to grow under atmospheric air but can grow when elevated CO2 is present, can be complemented by S. aureus mpsAB and vice versa. This mutual complementation experiments indicate that both the DIC transporter and CA represent a DIC concentrating system that can functionally substitute each other. Compared to the wild type, production of hemolytic toxins are less in S. aureus mps mutants and they also display less virulence in mouse model of infection. Phylogenetic analysis reveals that MpsAB homologs are ubiquitous in bacteria and frequently occur side-by-side on the genome. Interestingly, the majority of bacteria possess homologs of either MpsAB or CA, while both are present in some highly pathogenic species. Taken together, MpsAB is proposed to act as a DIC transporter or bicarbonate concentrating system, potentially operating as a sodium bicarbonate cotransporter. In a separate work, the mechanisms behind the host cell internalization triggered by Lpl proteins was elucidated. Lipoprotein-like lipoproteins (Lpls) is encoded by the S. aureus lpl cluster on a pathogenicity island named νSaα island which consists of 10 lpls paralogue genes. By using recombinant Lpl1 protein as a model of Lpls, the host receptor for Lpl-induced S. aureus USA300 invasion of human keratinocytes was identified as human heat shock protein Hsp90 via pull-down assay. Synthetic peptides which covers the Lpl1 sequence resulted in double to five-fold higher rate of S. aureus invasion in HaCaT cells and in primary human keratinocytes. Lpl-Hsp90 interaction stimulates F-actin formation, leading to an endocytosis-like engulfment of S. aureus
