Wei Yunyun, Qiu Jianfeng, Han Ziqiang, Wang Xuanyi, Zhang Hui, Hou Xinya, Lv Xiangwei, Mao Xiaolong
School of Radiology, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, 271016, China.
School of Radiology, Shandong First Medical University and Shandong Academy of Medical Sciences, Tai'an, 271000, China.
Biomater Res. 2023 Oct 5;27(1):97. doi: 10.1186/s40824-023-00443-1.
For some ICU patients, an artificial airway must be established with an endotracheal tube, but Candida albicans can easily adhere to the tube surface and form a biofilm, leading to potentially life threatening fungal infections. Therefore, it is urgent to prevent and reduce C. albicans infections introduced by the endotracheal tube. However, there are few antifungal drugs effective against C. albicans, and each of these drugs may have adverse effects on human cells. Saccharomyces boulardii is regarded as an alternative strategy to inhibit the adhesion of C. albicans, but it is affected by environmental stress. We hypothesized that it is feasible to strengthen the antagonistic ability of S. boulardii via encapsulating and genetically modification.
In this study, a bioactive material carrying the overexpressed MCP1 gene of Saccharomyces boulardii was constructed based on one-step photo-crosslinking. This material achieved spatial growth control of S. boulardii by encapsulating each S. boulardii cell within a hydrogel pore. The bioactive material was coated on an endotracheal tube and tested for its ability to inhibit the adhesion of C. albicans. Additionally, the material's antagonistic activity towards C. albicans was evaluated by detecting intracellular Adenosine-triphosphate content, reactive oxygen species level and the activity of antioxidative enzymes. Tissue invasion experiment was executed to further evaluate the anti-adhesion ability of S. boulardii bio-coating.
Encapsulating the overexpression of MCP1 by S. boulardii in hydrogel pores enhanced the viability of probiotics in the presence of high salt and oxidation stress. When used as the coating of an endotracheal tube, the S. boulardii bioactive material efficiently inhibited the adhesion of C. albicans by impairing the activities of superoxide dismutase and catalase and disturbing mitochondrial functions. In vivo, the S. boulardii bioactive material coating displayed good biocompatibility and reduced the host tissue invasion and virulence of C. albicans.
The integration of genetic modification and immobilization model breaks the bottleneck of previous application of microorganisms, and provides a new way to prevent fungal infections introduced by endotracheal tubes.
对于一些重症监护病房(ICU)患者,必须通过气管内插管建立人工气道,但白色念珠菌很容易粘附在插管表面并形成生物膜,从而导致可能危及生命的真菌感染。因此,预防和减少气管内插管引起的白色念珠菌感染迫在眉睫。然而,有效的抗白色念珠菌的抗真菌药物很少,并且每种药物都可能对人体细胞产生不良反应。布拉氏酵母菌被视为抑制白色念珠菌粘附的一种替代策略,但它会受到环境压力的影响。我们假设通过封装和基因改造来增强布拉氏酵母菌的拮抗能力是可行的。
在本研究中,基于一步光交联构建了一种携带布拉氏酵母菌过表达MCP1基因的生物活性材料。这种材料通过将每个布拉氏酵母菌细胞封装在水凝胶孔中来实现对其空间生长的控制。将该生物活性材料涂覆在气管内插管上,并测试其抑制白色念珠菌粘附的能力。此外,通过检测细胞内三磷酸腺苷含量、活性氧水平和抗氧化酶活性来评估该材料对白色念珠菌的拮抗活性。进行组织侵袭实验以进一步评估布拉氏酵母菌生物涂层的抗粘附能力。
在水凝胶孔中封装布拉氏酵母菌过表达的MCP1可增强益生菌在高盐和氧化应激条件下的活力。当用作气管内插管的涂层时,布拉氏酵母菌生物活性材料通过损害超氧化物歧化酶和过氧化氢酶的活性以及干扰线粒体功能,有效地抑制了白色念珠菌的粘附。在体内,布拉氏酵母菌生物活性材料涂层表现出良好的生物相容性,并降低了白色念珠菌对宿主组织的侵袭和毒力。
基因改造与固定化模型的结合打破了以往微生物应用的瓶颈,为预防气管内插管引起的真菌感染提供了一种新方法。