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The oral pathogen Aggregatibacter actinomycetemcomitans (Aa) resides in infection sites with many microbes, including commensal streptococci such as Streptococcus gordonii (Sg). During infection, Sg promotes the virulence of Aa by producing its preferred carbon source, l-lactate, a phenomenon referred to as cross-feeding. However, as with many streptococci, Sg also produces high levels of the antimicrobial hydrogen peroxide (H₂O₂), leading to the question of how Aa deals with this potent antimicrobial during coinfection. Here, we show that Aa possesses two complementary responses to H₂O₂: a detoxification or fight response mediated by catalase (KatA) and a dispersion or flight response mediated by Dispersin B (DspB), an enzyme that dissolves Aa biofilms. Using a murine abscess infection model, we show that both of these responses are required for Sg to promote Aa virulence. Although the role of …