Complex host genetic susceptibility to Staphylococcus aureus infections

Understanding of the host genetic susceptibility to carriage of, and infections, due to Staphylococcus aureus, a nosocomial pathogen, is still in its nascent stages. Mouse models show variable susceptibility to S. aureus infections across mouse strains and disease models with roles for signaling pathways involving Toll-like receptors (TLR-1, TLR-2, and TLR-6), interleukins (IL-4, IL-6, IL-10, and IL-13), chemokines [CXC ligand (CXCL)-1 and CXCL-2], and T helper (Th)1/Th2 responses. Genome-wide association studies (GWASs) for carriage in humans identified SNPs in IL4, DEFB1, CRP, and VDR for persistent nasal carriage. NR3C1 haplotypes may either enhance risk or provide protection from colonization. GWASs for all S. aureus diseases have suggested roles for DAPK3, a kinase, and XRN1, a nuclease, while CDON could have a role in complicated bacteremia. More studies are needed to identify host susceptibility genes along with confirmation from functional assays.