Pathogens often colonize the host as polymicrobial communities; however, much remains to be learnt about how microbial interspecies interactions alter bacterial behaviour. Co-infection with Staphylococcus aureus and Pseudomonas aeruginosa is common in patients with cystic fibrosis and has been associated with increased virulence and pulmonary decline. In this study, Armbruster et al. report that the S. aureus adhesin, staphylococcal protein A (SpA; an extracellular virulence factor that impedes host immune responses) inhibits the formation of biofilms by specific clinical isolates of P. aeruginosa and IgG-mediated phagocytosis by host neutrophils. The authors went on to show that SpA exerts these effects by binding to Psl polysaccharide and the PilA protein component of type IV pili, two surface molecules of P. aeruginosa that have been implicated in adhesion and cell–cell interactions. Thus, the results of this study suggest that secreted SpA alters persistence and host interaction of P. aeruginosa during co-infection.