Catalase produced by protects from HO stress-one more piece in the cross-kingdom synergism puzzle.

Co-infection with and is associated with dental caries, and their co-cultivation results in enhanced biofilm matrix production that contributes to increased virulence and caries risk. Moreover, the catalase-negative demonstrates increased oxidative stress tolerance when co-cultivated in biofilms with a catalase-producing yeast. Here, we sought to obtain mechanistic insights into the increased HO tolerance of when co-cultivated with clinical isolates of , and . Additionally, the SC5314 laboratory strain, its catalase mutant (SC5314), and UA159 and its glucosyltransferase B/C mutant (UA159) were grown as single- and dual-species biofilms. Time-kill assays revealed that upon acute HO challenge, the survival rates of in dual-species biofilms with the clinical isolates and SC5314 were greater than when paired with SC5314 or as a single-species biofilm. Importantly, this protection was independent of glucan production through GtfB/C. Transwell assays and treatment with HO-pre-stimulated SC5314 supernatant revealed that this protection is contact-dependent. Biofilm stability assays with sublethal HO or peroxigenic A12 challenge resulted in biomass reduction of single-species UA159 and dual-species with SC5314 biofilms compared to UA159 biofilms co-cultured with SC5314. oxidative stress genes were upregulated in single-species biofilms when exposed to HO but not when was co-cultivated with SC5314. Here, we uncovered a novel, contact-dependent, synergistic interaction in which the catalase of protects against HO. IMPORTANCE It is well established that co-infection with the gram-positive caries-associated bacterium and the yeast pathobiont results in aggressive forms of caries in humans and animal models. Together, these microorganisms form robust biofilms through enhanced production of extracellular polysaccharide matrix. Further, co-habitation in a biofilm community appears to enhance these microbes' tolerance to environmental stressors. Here, we show that catalase produced by protects from HO stress in a biofilm matrix-independent manner. Our findings uncovered a novel synergistic trait between these two microorganisms that could be further exploited for dental caries prevention and control.