Figure 7. Mechanism of USA300-induced lung injury.

Schematics show USA300 MA formation in an alveolar niche. Rapid interactions between USA300 and the alveolar epithelium initiate lung injury as follows: (1) Within minutes, inhaled USA300 stabilize in alveolar niches by forming solute-impermeable MAs through bacterial-bacterial, PhnD-mediated interactions. (2) Microaggregated bacteria rapidly release Hla toxin, leading to membrane damage in the localized MA-associated alveolar epithelial membrane. (3) Cytosolic Ca²⁺ increases in the MA-associated epithelium and (4) spreads to uninfected alveoli through connexin 43–containing GJs, widely amplifying the spatial extent of the alveolar damage. (5) Subsequently, there is mitochondrial depolarization, surfactant secretion inhibition, and alveolar edema. Alv, alveolus.