New metabolic signature for Chagas disease reveals sex steroid perturbation in humans and mice
Makan Golizeh,
John Nam,
Eric Chatelain,
Yves Jackson,
Leanne B. Ohlund,
Asieh Rasoolizadeh,
Fabio Vasquez Camargo,
Louiza Mahrouche,
Alexandra Furtos,
Lekha Sleno,
Momar Ndao
Affiliations
Makan Golizeh
Department of Mathematical and Physical Sciences, Concordia University of Edmonton, Edmonton, Alberta, Canada; National Reference Centre for Parasitology, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada
John Nam
National Reference Centre for Parasitology, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada; Infectious Diseases and Immunity in Global Health (IDIGH) Program, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada
Eric Chatelain
Drugs for Neglected Diseases initiative, Geneva, Switzerland
Yves Jackson
Division of Primary Care Medicine, Geneva University Hospitals and University of Geneva, Geneva, Switzerland
Leanne B. Ohlund
Chemistry Department, Université du Québec à Montréal, Montreal, Quebec, Canada; Center for Excellence in Research on Orphan Diseases – Fondation Courtois (CERMO-FC), Montreal, Quebec, Canada
Asieh Rasoolizadeh
National Reference Centre for Parasitology, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada
Fabio Vasquez Camargo
National Reference Centre for Parasitology, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada
Louiza Mahrouche
Chemistry Department, Regional Centre for Mass Spectrometry, Université de Montréal, Montreal, Quebec, Canada
Alexandra Furtos
Chemistry Department, Regional Centre for Mass Spectrometry, Université de Montréal, Montreal, Quebec, Canada
Lekha Sleno
Chemistry Department, Université du Québec à Montréal, Montreal, Quebec, Canada; Center for Excellence in Research on Orphan Diseases – Fondation Courtois (CERMO-FC), Montreal, Quebec, Canada; Corresponding author.
Momar Ndao
National Reference Centre for Parasitology, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada; Infectious Diseases and Immunity in Global Health (IDIGH) Program, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada; Department of Experimental Medicine, McGill University, Montreal, Quebec, Canada; Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada; Corresponding author.
The causative agent of Chagas disease (CD), Trypanosoma cruzi, claims thousands of lives each year. Current diagnostic tools are insufficient to ensure parasitological detection in chronically infected patients has been achieved. A host-derived metabolic signature able to distinguish CD patients from uninfected individuals and assess antiparasitic treatment efficiency is introduced. Serum samples were collected from chronic CD patients, prior to and three years after treatment, and subjected to untargeted metabolomics analysis against demographically matched CD-negative controls. Five metabolites were confirmed by high-resolution tandem mass spectrometry. Several database matches for sex steroids were significantly altered in CD patients. A murine experiment corroborated sex steroid perturbation in T. cruzi-infected mice, particularly in male animals. Proteomics analysis also found increased steroidogenesis in the testes of infected mice. Metabolic alterations identified in this study shed light on the pathogenesis and provide the basis for developing novel assays for the diagnosis and screening of CD patients.
