Evaluation of pathogen specific urinary peptides in tick-borne illnesses

Ruben Magni, Raghad Almofee, Sameen Yusuf, Claudius Mueller, Ngoc Vuong, Mahmood Almosuli, Minh Thu Hoang, Katherine Meade, Ish Sethi, Nuha Mohammed, Robyn Araujo, Teresa Kaza McDonald, Paul Marcelli, Virginia Espina, Brianna Kim, Anja Garritsen, Christine Green, Paul Russo, Weidong Zhou, Iosif VaismanEmanuel F. Petricoin, Deborah Hoadley, Robert E. Molestina, Hope McIntyre, Lance A. Liotta, Alessandra Luchini*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageEnglish
Article number19340
JournalScientific Reports
Volume10
Issue number1
DOIs
StatePublished - Dec 2020
Externally publishedYes

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