The contribution of biofilms to virulence and as a barrier to treatment is well-established for Staphylococcus aureus and Enterococcus faecalis, both nosocomial pathogens frequently isolated from biofilm-associated infections. Despite frequent co-isolation, their interactions in biofilms have not been well-characterized. We report that in combination, these two species can give rise to augmented biofilms biomass that is dependent on the activation of E. faecalis aerobic respiration. In E. faecalis, respiration requires both exogenous heme to activate the cydAB-encoded heme-dependent cytochrome bd, and the availability of O₂. We determined that the ABC transporter encoded by cydDC contributes to heme import. In dual species biofilms, S. aureus provides the heme to activate E. faecalis respiration. S. aureus mutants deficient in heme biosynthesis were unable to augment biofilms whereas heme alone is sufficient to augment E. faecalis mono-species biofilms. Our results demonstrate that S. aureus-derived heme, likely in the form of released hemoproteins, promotes E. faecalis biofilm formation, and that E. faecalis gelatinase activity facilitates heme extraction from hemoproteins. This interspecies interaction and metabolic cross-feeding may explain the frequent co-occurrence of these microbes in biofilm-associated infections.

生物膜对毒力的贡献和作为治疗障碍的作用在金黄色葡萄球菌和粪肠球菌中得到了很好的证实，这两种院内病原体经常从生物膜相关感染中分离出来。尽管经常共同隔离，但它们在生物膜中的相互作用尚未得到很好的表征。我们报告说，这两个物种结合起来可以产生增强的生物膜生物量，这取决于粪肠球菌有氧呼吸的激活。在粪肠球菌中，呼吸作用既需要外源血红素来激活cydAB编码的血红素依赖性细胞色素bd，也需要 O _{2的可用性}. 我们确定由cydDC编码的 ABC 转运蛋白有助于血红素导入。在双物种生物膜中，金黄色葡萄球菌提供激活粪肠球菌呼吸的血红素。血红素生物合成缺陷的金黄色葡萄球菌突变体无法增加生物膜，而仅血红素就足以增加粪肠球菌单种生物膜。我们的结果表明，金黄色葡萄球菌衍生的血红素（可能以释放的血红素蛋白的形式）促进粪肠球菌生物膜的形成，并且粪肠球菌明胶酶活性有助于从血红素蛋白中提取血红素。这种种间相互作用和代谢交叉喂养可以解释这些微生物在生物膜相关感染中的频繁共存。