Key message
Staphylococcus aureus is a deadly microbe that multiplexes death-effector deoxyribonucleosides to kill phagocytes by an as-yet-unknown mechanism. Here, we illustrate that staphylococcal effector-nucleosides drive damage of mitochondria and subsequent activation of the intrinsic pathway of apoptosis in abscess-invading macrophages, a devastating event that shapes infectious disease outcomes in mammalian hosts.
Translational perspective
Given that S. aureus-derived effector-nucleosides substantially contribute to staphylococcal immune evasion and disease pathogenesis, our discoveries along with the identification of human factors that increase the susceptibility of the host toward a predominant pathogen will aid in the design of new anti-infective and host-directed therapeutic agents against which S. aureus cannot develop resistance mechanisms.
Original Publication
Nicoletta Schwermann, Rita Haller, Sebastian Koch, Guntram A. Grassl, Volker Winstel
Pathogen-driven nucleotide overload triggers mitochondria-centered cell death in phagocytes
PLOS Pathogens, 2023