Fig. 6: Summary of results.
From: Collagen binding adhesin restricts Staphylococcus aureus skin infection
a The N-terminal collagen-like domain of C1q binds to Cna and reduces complement deposition and opsonophagocytosis. Expression of Cna allows S. aureus to bind to collagen and restrict bacterial contact with immune cells such as neutrophils. Bacteria that are taken up are eliminated by neutrophils. b The neutrophil response to Cna(+) S. aureus activates the release of the neutrophil chemokine KC, causing an influx of neutrophils. Macrophages at the site of infection release MMP-12 and leukotriene B4 which interacts with its receptor, BLT1, on neutrophils, macrophages and other cells. This causes the activation of MMP-9 which cleaves collagen, forming the highly inflammatory molecule, Pro-Gly-Pro. MMP-2 (collagenase) is released by epithelial cells and fibroblasts contributing to inflammation and production of Pro-Gly-Pro. Neutrophil receptors CXCR1/2 interact with KC and Pro-Gly-Pro which causes the influx of additional neutrophils, thereby controlling infection. c Bacteria lacking the ability to express Cna cannot directly bind to collagen. C1q is not sequestered in the absence of Cna, causing increased bacterial uptake by neutrophils. This allows direct contact between neutrophils and bacteria. This leads to neutrophil lysis and inflammation. d The neutrophil response to Cna(−) bacteria results in neutrophil lysis, release of higher levels of KC and influx of a larger number of neutrophils (compared to Cna(+) conditions). This amplifies the cycle of inflammation shown in c and leads to the production of significantly higher levels of leukotriene hydrolase 4 (LTAH4) from macrophages (as compared to Cna(+)), an enzyme that breaks down LTB4. Due to the influx and death of neutrophils this inflammation cycle perpetuates. Created in BioRender. Urbina Martinez, M. (2026) https://BioRender.com/rk7djos.
