Polymicrobial biofilms are a hallmark of chronic wound infection. The forces governing assembly and maturation of these microbial ecosystems are largely unexplored but the consequences on host response and clinical outcome can be significant. In the context of wound healing, formation of a biofilm and a stable microbial community structure is associated with impaired tissue repair resulting in a non-healing chronic wound. These types of wounds can persist for years simmering below the threshold of classically defined clinical infection (which includes heat, pain, redness, and swelling) and cycling through phases of recurrent infection. In the most severe outcome, amputation of lower extremities may occur if spreading infection ensues. Here we take an ecological perspective to study priority effects and competitive exclusion on overall biofilm community structure in a three-membered community comprised of strains of Staphylococcus aureus, Citrobacter freundii, and Candida albicans derived from a chronic wound. We show that both priority effects and inter-bacterial competition for binding to C. albicans biofilms significantly shape community structure on both abiotic and biotic substrates, such as ex vivo human skin wounds. We further show attachment of C. freundii to C. albicans is mediated by mannose-binding lectins. Co-cultures of C. freundii and C. albicans trigger the yeast-to-hyphae transition, resulting in a significant increase in neutrophil death and inflammation compared to either species alone. Collectively, the results presented here facilitate our understanding of fungal-bacterial interactions and their effects on host-microbe interactions, pathogenesis, and ultimately, wound healing.

多种微生物生物膜是慢性伤口感染的标志。控制这些微生物生态系统组装和成熟的力量在很大程度上尚未被探索，但对宿主反应和临床结果的影响可能是重大的。在伤口愈合的背景下，生物膜和稳定的微生物群落结构的形成与组织修复受损相关，导致慢性伤口不愈合。这些类型的伤口可以持续数年，低于经典定义的临床感染（包括热、疼痛、发红和肿胀）的阈值，并在反复感染的阶段中循环。在最严重的结果中，如果感染扩散，可能会导致下肢截肢。在这里，我们从生态角度研究了由金黄色葡萄球菌、弗氏柠檬酸杆菌和白色念珠菌菌株组成的三元群落中整体生物膜群落结构的优先效应和竞争排斥。我们表明，与白色念珠菌生物膜结合的优先效应和细菌间竞争都显着塑造了非生物和生物基质（例如离体人类皮肤伤口）上的群落结构。我们进一步表明弗氏念珠菌与白色念珠菌的附着是由甘露糖结合凝集素介导的。弗氏念珠菌和白色念珠菌的共培养会引发酵母向菌丝的转变，与单独使用任一物种相比，导致中性粒细胞死亡和炎症显着增加。总的来说，这里提出的结果有助于我们了解真菌-细菌相互作用及其对宿主-微生物相互作用、发病机制以及最终伤口愈合的影响。