A Mycobacterium tuberculosis fingerprint in human breath allows tuberculosis detection

Sergio Fabián Mosquera-Restrepo, Sophie Zuberogoïtia, Lucie Gouxette, Emilie Layre, Martine Gilleron, Alexandre Stella, David Rengel, Odile Burlet-Schiltz, Ana Cecilia Caro, Luis F. Garcia, César Segura, Carlos Alberto Peláez Jaramillo, Mauricio Rojas () and Jérôme Nigou ()
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Sergio Fabián Mosquera-Restrepo: Faculty of Medicine, University Research Headquarters (SIU), University of Antioquia (UdeA)
Sophie Zuberogoïtia: University of Toulouse, CNRS, University of Toulouse III-Paul Sabatier
Lucie Gouxette: University of Toulouse, CNRS, University of Toulouse III-Paul Sabatier
Emilie Layre: University of Toulouse, CNRS, University of Toulouse III-Paul Sabatier
Martine Gilleron: University of Toulouse, CNRS, University of Toulouse III-Paul Sabatier
Alexandre Stella: University of Toulouse, CNRS, University of Toulouse III-Paul Sabatier
David Rengel: University of Toulouse, CNRS, University of Toulouse III-Paul Sabatier
Odile Burlet-Schiltz: University of Toulouse, CNRS, University of Toulouse III-Paul Sabatier
Ana Cecilia Caro: Faculty of Exact and Natural Sciences. University of Antioquia (UdeA)
Luis F. Garcia: Faculty of Medicine, University Research Headquarters (SIU), University of Antioquia (UdeA)
César Segura: University of Antioquia (UdeA)
Carlos Alberto Peláez Jaramillo: Faculty of Exact and Natural Sciences. University of Antioquia (UdeA)
Mauricio Rojas: Faculty of Medicine, University Research Headquarters (SIU), University of Antioquia (UdeA)
Jérôme Nigou: University of Toulouse, CNRS, University of Toulouse III-Paul Sabatier

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract An estimated one-third of tuberculosis (TB) cases go undiagnosed or unreported. Sputum samples, widely used for TB diagnosis, are inefficient at detecting infection in children and paucibacillary patients. Indeed, developing point-of-care biomarker-based diagnostics that are not sputum-based is a major priority for the WHO. Here, in a proof-of-concept study, we tested whether pulmonary TB can be detected by analyzing patient exhaled breath condensate (EBC) samples. We find that the presence of Mycobacterium tuberculosis (Mtb)-specific lipids, lipoarabinomannan lipoglycan, and proteins in EBCs can efficiently differentiate baseline TB patients from controls. We used EBCs to track the longitudinal effects of antibiotic treatment in pediatric TB patients. In addition, Mtb lipoarabinomannan and lipids were structurally distinct in EBCs compared to ex vivo cultured bacteria, revealing specific metabolic and biochemical states of Mtb in the human lung. This provides essential information for the rational development or improvement of diagnostic antibodies, vaccines and therapeutic drugs. Our data collectively indicate that EBC analysis can potentially facilitate clinical diagnosis of TB across patient populations and monitor treatment efficacy. This affordable, rapid and non-invasive approach seems superior to sputum assays and has the potential to be implemented at point-of-care.

Date: 2022
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DOI: 10.1038/s41467-022-35453-5

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