Arnold Kim, Gómez-Mejia Alejandro, de Figueiredo Miguel, Boccard Julien, Singh Kapil Dev, Rudaz Serge, Sinues Pablo, Zinkernagel Annelies S
University Children's Hospital Basel (UKBB), Basel, 4056, Switzerland.
Department of Biomedical Engineering, University of Basel, Allschwil, 4123, Switzerland.
BMC Infect Dis. 2024 Dec 27;24(1):1467. doi: 10.1186/s12879-024-10371-7.
The ability to detect pathogenic bacteria before the onsets of severe respiratory symptoms and to differentiate bacterial infection allows to improve patient-tailored treatment leading to a significant reduction in illness severity, comorbidity as well as antibiotic resistance. As such, this study refines the application of the non-invasive Secondary Electrospray Ionization-High Resolution Mass Spectrometry (SESI-HRMS) methodology for real-time and early detection of human respiratory bacterial pathogens in the respiratory tract of a mouse infection model.
A real-time analysis of changes in volatile metabolites excreted by mice undergoing a lung infection by Staphylococcus aureus or Streptococcus pneumoniae were evaluated using a SESI-HRMS instrument. The infection status was confirmed using classical CFU enumeration and tissue histology. The detected VOCs were analyzed using a pre- and post-processing algorithm along with ANOVA and RASCA statistical evaluation methods.
Characteristic changes in the VOCs emitted from the mice were detected as early as 4-6 h post-inoculation. Additionally, by using each mouse as its own baseline, we mimicked the inherent variation within biological organism and reported significant variations in 25 volatile organic compounds (VOCs) during the course of a lung bacterial infection.
the non-invasive SESI-HRMS enables real-time detection of infection specific VOCs. However, further refinement of this technology is necessary to improve clinical patient management, treatment, and facilitate decisions regarding antibiotic use due to early infection detection.
在严重呼吸道症状发作前检测致病细菌并区分细菌感染的能力,有助于改进针对患者的个性化治疗,从而显著降低疾病严重程度、合并症以及抗生素耐药性。因此,本研究优化了非侵入性二次电喷雾电离-高分辨率质谱(SESI-HRMS)方法在小鼠感染模型呼吸道中实时早期检测人类呼吸道细菌病原体的应用。
使用SESI-HRMS仪器对感染金黄色葡萄球菌或肺炎链球菌的小鼠呼出的挥发性代谢物变化进行实时分析。通过经典的菌落形成单位(CFU)计数和组织组织学确认感染状态。使用预处理和后处理算法以及方差分析(ANOVA)和随机不对称成分分析(RASCA)统计评估方法对检测到的挥发性有机化合物(VOC)进行分析。
早在接种后4-6小时就检测到小鼠呼出的VOCs有特征性变化。此外,通过将每只小鼠作为自身基线,我们模拟了生物体内的固有变异,并报告了肺部细菌感染过程中25种挥发性有机化合物(VOC)有显著变化。
非侵入性SESI-HRMS能够实时检测感染特异性VOC。然而,由于早期感染检测,需要进一步改进该技术以改善临床患者管理、治疗并促进抗生素使用决策。