Mechanistic insights into the pathogenesis and therapeutic recalcitrance of <i>Staphylococcus aureus</i> osteomyelitis

SUMMARY Osteomyelitis refers to inflammation in the bone and is most often a consequence of bacterial infection. The most common cause, and the pathogen that causes the most severe form of infection, is Staphylococcus aureus. S. aureus is a common commensal of healthy humans, and this contributes to its predominance as a cause of osteomyelitis, but this does not account for the severity of S. aureus bone infections or their therapeutic recalcitrance to conventional antibiotic therapy. Clinical characteristics of osteomyelitis implicated in this regard include cortical bone destruction resulting in a compromised local blood supply, formation of a biofilm, the ability to invade and survive inside osteoblasts, osteoclasts, and osteocytes, the formation of small-colony variants and persister cells, and invasion of the osteocyte lacuno-canalicular network. This review summarizes evidence implicating these features in the pathogenesis and therapeutic recalcitrance of osteomyelitis, and the attributes of S. aureus that contribute to these features and define S. aureus as the predominant orthopedic pathogen.