Evaluation of pathogen specific urinary peptides in tick-borne illnesses.

Evaluation of pathogen specific urinary peptides in tick-borne illnesses.
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DOI:
10.1038/s41598-020-75051-3
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发表时间:
2020-11-09
期刊:
影响因子:
4.6
通讯作者:
Luchini A
Luchini A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Magni R;Almofee R;Yusuf S;Mueller C;Vuong N;Almosuli M;Hoang MT;Meade K;Sethi I;Mohammed N;Araujo R;McDonald TK;Marcelli P;Espina V;Kim B;Garritsen A;Green C;Russo P;Zhou W;Vaisman I;Petricoin EF 3rd;Hoadley D;Molestina RE;McIntyre H;Liotta LA;Luchini A

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通过纳米技术增强的质谱分析可以实现以前无法达到的灵敏度来表征尿病原体衍生的肽。我们利用亲和水凝胶颗粒增强的质谱法(分析灵敏度≥2.5 pg/mL)来研究患有以下疾病的患者尿液中脱落的蜱病原体特异性蛋白质:(1) 游走性红斑皮疹和急性症状,(2) 治疗后莱姆病综合征 (PTLDS),以及 (3) 临床怀疑蜱传疾病 (TBI)。目标病原体为疏螺旋体、巴贝虫、无形体、立克次体、埃利希体、巴尔通体、弗朗西斯菌、波瓦桑病毒、蜱传脑炎病毒和科罗拉多蜱热病毒。特异性的定义是与蜱传病原体蛋白 100% 的氨基酸序列同一性、相关病原体的进化分类学验证,以及与人类或其他生物体没有同一性。通过截断两种病原体肽,9/10 的急性莱姆疏螺旋体病患者结果呈阳性,而我们在 250 名对照中发现零假阳性。在 40% 的 PTLDS 和 TBI 患者样本中鉴定出两种或多种病原体肽(上述第 2 类和第 3 类,n = 59/148)。总共鉴定出了 279 种独特的蜱传病原体衍生肽。病原体特异性肽的数量与患者报告的症状的存在或不存在直接相关(序数回归伪R2 = 0.392,p = 0.010)。增强型质谱分析是研究蜱传病原体感染的新工具。
Mass spectrometry enhanced by nanotechnology can achieve previously unattainable sensitivity for characterizing urinary pathogen-derived peptides. We utilized mass spectrometry enhanced by affinity hydrogel particles (analytical sensitivity = 2.5 pg/mL) to study tick pathogen-specific proteins shed in the urine of patients with (1) erythema migrans rash and acute symptoms, (2) post treatment Lyme disease syndrome (PTLDS), and (3) clinical suspicion of tick-borne illnesses (TBI). Targeted pathogens were Borrelia, Babesia, Anaplasma, Rickettsia, Ehrlichia, Bartonella, Francisella, Powassan virus, tick-borne encephalitis virus, and Colorado tick fever virus. Specificity was defined by 100% amino acid sequence identity with tick-borne pathogen proteins, evolutionary taxonomic verification for related pathogens, and no identity with human or other organisms. Using a cut off of two pathogen peptides, 9/10 acute Lyme Borreliosis patients resulted positive, while we identified zero false positive in 250 controls. Two or more pathogen peptides were identified in 40% of samples from PTLDS and TBI patients (categories 2 and 3 above, n = 59/148). Collectively, 279 distinct unique tick-borne pathogen derived peptides were identified. The number of pathogen specific peptides was directly correlated with presence or absence of symptoms reported by patients (ordinal regression pseudo-R2 = 0.392, p = 0.010). Enhanced mass spectrometry is a new tool for studying tick-borne pathogen infections.
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