School of Biochemistry and Biotechnology, University of the Punjab, Lahore, 54590, Pakistan.
Center for Biosensor Research and Development, University of the Punjab, Lahore, 54590, Pakistan.
Appl Biochem Biotechnol. 2024 Oct;196(10):6915-6935. doi: 10.1007/s12010-024-04892-9. Epub 2024 Feb 29.
Staphylococcus aureus is a major source of bacteremia and develops several complications, causing high morbidity and mortality. Rapid identification and detection of these bacteria have become an important issue for biomedical applications. Herein, an optical method based on a modified fluorescence in situ hybridization (FISH) approach has been established using DNA hybridization technology for the swift detection of pathogenic S. aureus from clinical samples. The platform was constructed with single-stranded genomic DNA and microbial colony by directly immobilizing in agarose-polyvinyl alcohol (AG-PVA) hydrogel on the surface of a glass slide. The probe was based on an elongation factor encoding the tuf gene, which binds with equal affinity to single-stranded DNA targets as well as surface proteins on microbial cells. The probe was labeled with MFP488 fluorophore having excitation wavelength 501 nm. The hybridization of the labeled probe with the target DNA and surface proteins was carried out under optimal FISH conditions, and the detection of bacteria was based on temporary field excitation of the labeled probe under a fluorescence microscope. Positive hybridization signals were detected by high fluorescence intensity. In comparison to genomic DNA, robust signals were observed with microbial cells, perhaps due to the moonlighting effect of the elongation factor Tu (Ef-Tu) expressed on the surface of bacterial cells. The applicability of the developed platform was tested on pediatric nasal samples, and results were verified with real-time qPCR. The designed platform is stable and sensitive, and after detailed optimization, a portable structure for on-site detection of pathogenic bacteria from clinical samples can be produced.
金黄色葡萄球菌是菌血症的主要来源,并会引发多种并发症,导致高发病率和死亡率。快速识别和检测这些细菌已成为生物医学应用的一个重要问题。在此,我们建立了一种基于改良荧光原位杂交(FISH)方法的光学方法,该方法利用 DNA 杂交技术,用于从临床样本中快速检测致病的金黄色葡萄球菌。该平台是通过将单链基因组 DNA 和微生物菌落直接固定在琼脂糖-聚乙烯醇(AG-PVA)水凝胶上构建的,该水凝胶位于载玻片的表面。探针基于编码延伸因子的 tuf 基因,该基因与单链 DNA 靶标以及微生物细胞表面蛋白具有同等亲和力。探针用激发波长为 501nm 的 MFP488 荧光染料标记。标记探针与目标 DNA 和表面蛋白的杂交是在最佳 FISH 条件下进行的,并且细菌的检测是基于在荧光显微镜下对标记探针进行临时场激发。通过高荧光强度检测到阳性杂交信号。与基因组 DNA 相比,在微生物细胞中观察到了更强的信号,这可能是由于细菌细胞表面表达的延伸因子 Tu(Ef-Tu)的 moonlighting 效应。该开发平台的适用性在儿科鼻腔样本上进行了测试,并与实时 qPCR 进行了验证。设计的平台稳定且灵敏,经过详细优化后,可以生产出用于现场检测临床样本中致病菌的便携式结构。