Metabolite Profiles of the Cerebrospinal Fluid in Neurosyphilis Patients Determined by Untargeted Metabolomics Analysis.

Li-Li Liu,Hui-Lin Zhang,Man-Li Tong,Jian-Jun Niu,Wei Chen,Jiang-Hua Yan,Xi Luo,Yong Lin,Tian-Ci Yang,Li-Rong Lin

doi:10.3389/fnins.2019.00150

Li-Li Liu, Hui-Lin Zhang + Show 8 more

Open Access

https://doi.org/10.3389/fnins.2019.00150

Copy DOI

Abstract

The mechanism underlying the stealth property of neurosyphilis is still unclear. Global metabolomics analysis can provide substantial information on energy metabolism, physiology and possible diagnostic biomarkers and intervention strategies for pathogens. To gain better understanding of the metabolic mechanism of neurosyphilis, we conducted an untargeted metabolomics analysis of cerebrospinal fluid (CSF) from 18 neurosyphilis patients and an identical number of syphilis/non-neurosyphilis patients and syphilis-free patients using the Agilent, 1290 Infinity LC system. The raw data were normalized and subjected to subsequent statistical analysis by MetaboAnalyst 4.0. Metabolites with a variable importance in projection (VIP) greater than one were validated by Student’s T-test. A total of 1,808 molecular features were extracted from each sample using XCMS software, and the peak intensity of each feature was obtained. Partial-least squares discrimination analysis provided satisfactory separation by comparing neurosyphilis, syphilis/non-neurosyphilis and syphilis-free patients. A similar trend was obtained in the hierarchical clustering analysis. Furthermore, several metabolites were identified as significantly different by Student’s T-test, including L-gulono-gamma-lactone, D-mannose, N-acetyl-L-tyrosine, hypoxanthine, and S-methyl-5′-thioadenosine. Notably, 87.369-fold and 7.492-fold changes of N-acetyl-L-tyrosine were observed in neurosyphilis patients compared with syphilis/non-neurosyphilis patients and syphilis-free patients. These differential metabolites are involved in overlapping pathways, including fructose and mannose metabolism, lysosomes, ABC transporters, and galactose metabolism. Several significantly expressed metabolites were identified in CSF from neurosyphilis patients, including L-gulono-gamma-lactone, D-mannose, N-acetyl-L-tyrosine, and hypoxanthine. These differential metabolites could potentially improve neurosyphilis diagnostics in the future. The role of these differential metabolites in the development of neurosyphilis deserves further exploration.

Highlights

Syphilis is a common sexually transmitted disease worldwide, and the causative pathogen is the spirochete Treponema pallidum (Tong et al, 2013; Giacani and Lukehart, 2014)
We conducted an untargeted metabolomics analysis on cerebrospinal fluid (CSF) collected from neurosyphilis patients to gain a better understanding of the metabolic changes of neurosyphilis patients
We evaluated the experimental process by Partial-least squares discrimination analysis (PLS-DA) and hierarchical clustering analysis, and clear separation between groups was found

Summary

Introduction

Syphilis is a common sexually transmitted disease worldwide, and the causative pathogen is the spirochete Treponema pallidum (Tong et al, 2013; Giacani and Lukehart, 2014). The stealth property of T. pallidum is responsible for the obstacles currently encountered in the treatment and prevention of syphilis. Previous studies have proposed that the slow replication cycle of T. pallidum in vivo may be one of the reasons for the diminished immune response and clinical symptoms after infection (Wicher et al, 2000; Deka et al, 2013). The limited energy metabolic capacity of T. pallidum is responsible for the slow replication cycle and inability to survive outside mammalian cells of this pathogen (Deka et al, 2015). Endogenous metabolites are an excellent reflection of the metabolic process of pathogens in hosts

Methods

Results

Conclusion