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bioRxiv · 10.1101/2025.03.13.643069

The Staphylococcus aureus prophage-encoded SSBP attenuates virulence and enhances IL-6-mediated macrophage clearance

Ahmad-Mansour, N.·Abi Najem, C. N.·Martin, M.·Plumet, L.·Huc-Brandt, S.·Morsli, M.·Francois, P.·Sotto, A.·Dunyach-Remy, C.·Lavigne, J.-P.·MOLLE, V.
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Abstract

Pathogens often manipulate host immune responses to promote infection. Here, we describe a novel mechanism by which a secreted prophage-encoded single-stranded DNA-binding protein (SSBP) attenuates Staphylococcus aureus virulence while enhancing host immune defenses. SSBP, encoded by the ROSA-like prophage in a colonizing, reduced-virulence strain of S. aureus (NSA1385), significantly increases bacterial susceptibility to macrophage-mediated killing in vitro and reduces pathogenicity in a zebrafish infection model. Treatment with purified recombinant SSBP decreases bacterial survival within macrophages and demonstrates therapeutic potential. Notably, SSBP activates macrophages via interleukin-6 (IL-6), a pro-inflammatory cytokine that promotes bacterial clearance and macrophage activation. These findings uncover an unexpected prophage-derived mechanism in a colonizing S. aureus strain that attenuates virulence while stimulating host immunity, offering promising avenues for anti-infective therapies and immunomodulatory strategies.

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Ahmad-Mansour, N., Abi Najem, C. N., Martin, M., Plumet, L., Huc-Brandt, S., Morsli, M., Francois, P., Sotto, A., Dunyach-Remy, C., Lavigne, J.-P., MOLLE, V.. 2025-03-13. The Staphylococcus aureus prophage-encoded SSBP attenuates virulence and enhances IL-6-mediated macrophage clearance. https://doi.org/10.1101/2025.03.13.643069

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