Ayala Oscar D, Wakeman Catherine A, Pence Isaac J, Gaddy Jennifer A, Slaughter James C, Skaar Eric P, Mahadevan-Jansen Anita
Biophotonics Center , Vanderbilt University , 410 24th Avenue South , Nashville , Tennessee 37235 , United States.
Department of Biomedical Engineering , Vanderbilt University , 5824 Stevenson Center , Nashville , Tennessee 37232 , United States.
ACS Infect Dis. 2018 Aug 10;4(8):1197-1210. doi: 10.1021/acsinfecdis.8b00029. Epub 2018 Jun 25.
Staphylococcus aureus ( S. aureus) is a leading cause of hospital-acquired infections, such as bacteremia, pneumonia, and endocarditis. Treatment of these infections can be challenging since strains of S. aureus, such as methicillin-resistant S. aureus (MRSA), have evolved resistance to antimicrobials. Current methods to identify infectious agents in hospital environments often rely on time-consuming, multistep culturing techniques to distinguish problematic strains (i.e., antimicrobial resistant variants) of a particular bacterial species. Therefore, a need exists for a rapid, label-free technique to identify drug-resistant bacterial strains to guide proper antibiotic treatment. Here, our findings demonstrate the ability to characterize and identify microbes at the subspecies level using Raman microspectroscopy, which probes the vibrational modes of molecules to provide a biochemical "fingerprint". This technique can distinguish between different isolates of species such as Streptococcus agalactiae and S. aureus. To determine the ability of this analytical approach to detect drug-resistant bacteria, isogenic variants of S. aureus including the comparison of strains lacking or expressing antibiotic resistance determinants were evaluated. Spectral variations observed may be associated with biochemical components such as amino acids, carotenoids, and lipids. Mutants lacking carotenoid production were distinguished from wild-type S. aureus and other strain variants. Furthermore, spectral biomarkers of S. aureus isogenic bacterial strains were identified. These results demonstrate the feasibility of Raman microspectroscopy for distinguishing between various genetically distinct forms of a single bacterial species in situ. This is important for detecting antibiotic-resistant strains of bacteria and indicates the potential for future identification of other multidrug resistant pathogens with this technique.
金黄色葡萄球菌是医院获得性感染的主要原因,如菌血症、肺炎和心内膜炎。由于金黄色葡萄球菌菌株,如耐甲氧西林金黄色葡萄球菌(MRSA),已经对抗菌药物产生了耐药性,因此治疗这些感染具有挑战性。目前在医院环境中识别感染病原体的方法通常依赖于耗时的多步培养技术,以区分特定细菌物种的有问题菌株(即抗菌耐药变体)。因此,需要一种快速、无标记的技术来识别耐药细菌菌株,以指导正确的抗生素治疗。在这里,我们的研究结果表明,使用拉曼光谱能够在亚种水平上对微生物进行表征和识别,拉曼光谱通过探测分子的振动模式来提供生化“指纹”。该技术可以区分无乳链球菌和金黄色葡萄球菌等不同物种的分离株。为了确定这种分析方法检测耐药细菌的能力,我们评估了金黄色葡萄球菌的同基因变体,包括缺乏或表达抗生素抗性决定因素的菌株的比较。观察到的光谱变化可能与氨基酸、类胡萝卜素和脂质等生化成分有关。缺乏类胡萝卜素产生的突变体与野生型金黄色葡萄球菌和其他菌株变体区分开来。此外,还鉴定了金黄色葡萄球菌同基因菌株的光谱生物标志物。这些结果证明了拉曼光谱在原位区分单一细菌物种的各种遗传不同形式的可行性。这对于检测细菌的抗生素抗性菌株很重要,并表明了使用该技术未来识别其他多重耐药病原体的潜力。