MSCRAMM isoforms and Staphylococcus aureus infections of cardiovascular devices

Staphylococcus aureus is a commensal bacterium that may enter the bloodstream and may cause serious infection. It is a puzzle why S. aureus bacteremia in humans carrying an implanted cardiac device leads to infection of the device often but not always. We postulate that infection is a multistep pathogenic process where underlying genetic variation in the bacteria contributes to the bacteria's ability to transfer into the bloodstream and then to colonize the device. To investigate this hypothesis, we obtained whole genome sequences of 190 nasal and bloodstream isolates from patients with cardiovascular implants treated at one hospital. Whole genome single nucleotide polymorphisms has larger greater genetic diversity for isolates obtained from the nares (CDC) as compared to bloodstream isolates from cardiac device infected (CDI) and uninfected (CDU) groups. Sequence variation of the ~500 residue A-domain in published genomes for 107 global, reference strains for seven, cell wall anchored MSCRAMM proteins (clfA, clfB, fnbA, fnbB, sdrC, sdrD, sdrE) reveal that MSCRAMM alleles are associated with bacterial lineage. Structural protein models identified one allele of FnbpB that was significantly more common in the CDI population (p-value = 0.0091 ) compared to the other two groups CDC/CDU combined . Fibronectin-binding protein B (FnbpB) exhibited a significantly different rate of evolution compared to the other six MSCRAMMs. Furthermore, we identify a putative hotspot in FnbpB that could be targeted in the design of small molecule inhibitors of S. aureus infection.