Candida Pathogenesis in Surgery and Trauma

念珠菌属是医院内血流感染的第四大常见原因，而念珠菌属是医院内血流感染的第三大常见原因。在几乎所有的研究中，白色念珠菌占念珠菌属的50%至75%。尽管进行了适当的抗真菌治疗，死亡率仍为35%至75%。最高风险的患者包括免疫抑制患者、创伤患者和手术后患者，并且大部分病例发生在重症监护室。C.白色念珠菌经历可逆的形态转换，产生芽殖酵母和丝状形式，包括芽管、假菌丝和真菌丝。许多研究者认为，丝状形式是负责上皮入侵。然而，最近从小鼠肠外传播模型的数据表明，酵母细胞，而不是丝状形式，可能是更重要的C。白色念珠菌穿透肠上皮。我们的工作假设是，酵母细胞在这种真菌与肠上皮的相互作用（粘附和渗透）中发挥关键作用。一般的方法是使用野生型和良好表征的C。白色念珠菌突变株（具有形态转换缺陷），以在体外（培养的肠细胞）和体内（小鼠模型）挑战这一假设。因为C.光滑念珠菌最近成为念珠菌病的第二大最常见的原因，因为C。光滑假丝酵母是80多种已知假丝酵母中唯一不形成丝状体且仅以酵母形式存在的种，实验也集中在C.光滑的体外实验的目的是分别表征酵母和丝状形式与培养的肠上皮细胞的相互作用（粘附，内化，细胞内存活），测定系统包括ELISA和使用calcoflour和活体染料FUN-1的双荧光染料测定。小鼠模型包括抗生素诱导的肠道念珠菌定植、结扎肠袢和Stamper-Woodruff试验。细菌细胞壁产物（脂多糖和肽聚糖），地塞米松和缺氧对念珠菌肠外传播的影响也被阐明。如果我们的假设得到验证（酵母细胞在肠外传播中至关重要），那么设计更有效的体外敏感性测定以及更有效的预防和治疗方式的努力可能会更可靠地靶向酵母而不是菌丝元素。这样的知识应该加速我们诊断、治疗和控制系统性念珠菌病的能力。

Candida species are the fourth most common cause of nosocomial blood stream infections, and C. albicans accounts for 50% to 75% of Candida species in essentially all studies. Despite appropriate antifungal therapy, mortality is 35% to 75%. Patients at highest risk include immunosuppressed patients, trauma patients, and postsurgical patients, and a large proportion of cases occur in intensive care units. C. albicans undergoes reversible morphologic switching, producing budding yeast and filamentous forms that include germ tubes, pseudohyphae and true hyphae. Many investigators have assumed that filamentous forms are responsible for epithelial invasion. However, recent data from mouse models of extraintestinal dissemination indicate that the yeast cell, rather than filamentous forms, might be more important in C. albicans penetration of intestinal epithelium. Our working hypothesis is that yeast cells play a key role in interactions (adherence and penetration) of this fungus with the intestinal epithelium. The general approach is to use wild type and well-characterized C. albicans mutant strains (with defects in morphologic switching) to challenge this hypothesis in vitro (cultured enterocytes) and in vivo (mouse models). Because C. glabrata has recently emerged as the second most frequent cause of candidiasis, and because C. glabrata is the only species (of the more than 80 recognized Candida species) that does not form filaments and exists only in the yeast form, experiments also focus on C. glabrata. In vitro experiments are designed to separately characterize the interactions (adherence, internalization, intracellular survival) of yeast and filamentous forms with cultured enterocytes, and assay systems include ELISA and a double fluorochrome assay using calcoflour and the vital dye FUN-1. Mouse models include antibiotic-induced intestinal Candida colonization, ligated intestinal loops, and the Stamper-Woodruff assay. The effect of bacterial cell wall products (lipopolysaccharide and peptidoglycan), dexamethasone, and hypoxia on extraintestinal dissemination of Candida is also clarified. If our hypothesis is validated (that the yeast cell is of primary importance in extraintestinal dissemination), then efforts to design more effective in vitro susceptibility assays, as well as more effective prophylactic and therapeutic modalities, might more reliably target yeast rather than hyphal elements. Such knowledge should accelerate our ability to diagnose, treat, and control systemic candidiasis.