Staphylococcus aureus bloodstream infections: pathogenesis and regulatory mechanisms

•Phagocytes play both protective and detrimental roles in containing bloodstream S. aureus.•S. aureus hijacks the host coagulation system and uses it to bind host endothelium.•Strategies used by S. aureus to cause host damage are highly strain-dependent.•Multiple regulatory systems control S. aureus bloodstream infections, including Agr, ArlRS, and MgrA. Staphylococcus aureus is an opportunistic pathogen that normally colonizes the human anterior nares. At the same time, this pathogen is one of the leading causes of life-threatening bloodstream infections, such as sepsis and endocarditis. In this review we will present the current understanding of the pathogenesis of these invasive infections, focusing on the mechanisms of S. aureus clearance from the bloodstream by the immune system, and how this pathogen hijacks the host defense and coagulation systems and further interacts with the blood vessel endothelium. Additionally, we will delve into the regulatory mechanisms S. aureus employs during an invasive infection. These new insights into host–pathogen interactions show promising avenues for the development of novel therapies for treating bloodstream infections.