Open AccessTuberculostearic Acid-Containing Phosphatidylinositols as Markers of Bacterial Burden in Tuberculosis
Author(s) -
Julius Brandenburg,
Jan Heyckendorf,
Franziska Marwitz,
Nicole Zehethofer,
Lara Linnemann,
Nicolas Gisch,
Hande Karaköse,
Maja Reimann,
Katharina Kranzer,
Barbara Kalsdorf,
Patricia Sanchéz-Carballo,
Michael Weinkauf,
Verena Scholz,
Sven Malm,
Susanne Homolka,
Karoline I. Gaede,
Christian Herzmann,
Ulrich E. Schaible,
Christoph Hölscher,
Norbert Reiling,
Dominik Schwudke
Publication year - 2022
Publication title -
acs infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.324
H-Index - 39
ISSN - 2373-8227
DOI - 10.1021/acsinfecdis.2c00075
Subject(s) - tuberculosis , mycobacterium tuberculosis , peripheral blood mononuclear cell , colony forming unit , microbiology and biotechnology , biology , mycobacterium tuberculosis complex , immunology , population , pathogen , bacteria , virology , in vitro , medicine , pathology , biochemistry , genetics , environmental health
One-fourth of the global human population is estimated to be infected with strains of the Mycobacterium tuberculosis complex (MTBC), the causative agent of tuberculosis (TB). Using lipidomic approaches, we show that tuberculostearic acid (TSA)-containing phosphatidylinositols (PIs) are molecular markers for infection with clinically relevant MTBC strains and signify bacterial burden. For the most abundant lipid marker, detection limits of ∼10 2 colony forming units (CFUs) and ∼10 3 CFUs for bacterial and cell culture systems were determined, respectively. We developed a targeted lipid assay, which can be performed within a day including sample preparation─roughly 30-fold faster than in conventional methods based on bacterial culture. This indirect and culture-free detection approach allowed us to determine pathogen loads in infected murine macrophages, human neutrophils, and murine lung tissue. These marker lipids inferred from mycobacterial PIs were found in higher levels in peripheral blood mononuclear cells of TB patients compared to healthy individuals. Moreover, in a small cohort of drug-susceptible TB patients, elevated levels of these molecular markers were detected at the start of therapy and declined upon successful anti-TB treatment. Thus, the concentration of TSA-containing PIs can be used as a correlate for the mycobacterial burden in experimental models and in vitro systems and may prospectively also provide a clinically relevant tool to monitor TB severity.