Immunogenicity of Mycobacterial Extracellular Vesicles Isolated From Host-Related Conditions Informs About Tuberculosis Disease Status
Schirmer, Sebastian (University of Applied Sciences. Department of Medical Engineering and Biotechnology)
Rauh, Lucas (University of Applied Sciences. Department of Medical Engineering and Biotechnology)
Alebouyeh, Sogol (Universidad Autónoma de Madrid. Departamento de Medicina Preventiva y Salud Pública)
Delgado-Velandia, Mario (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública)
Salgueiro, Vivian C. (Universidad Autónoma de Madrid. Departamento de Medicina Preventiva y Salud Pública)
Lerma, Laura (Universidad Autónoma de Madrid. Departamento de Medicina Preventiva y Salud Pública)
Serrano-Mestre, José L. (Universidad Autónoma de Madrid. Departamento de Medicina Preventiva y Salud Pública)
Azkargorta, Mikel (Basque Research and Technology Alliance)
Elortza, Felix (Basque Research and Technology Alliance)
Lavín, José L. (Basque Research and Technology Alliance)
García, Maria Jesus (Universidad Autónoma de Madrid. Departamento de Medicina Preventiva y Salud Pública)
Tórtola Fernández, María Teresa (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Gola, Susanne (University of Applied Sciences. Department of Medical Engineering and Biotechnology)
Prados-Rosales, Rafael (Universidad Autónoma de Madrid. Departamento de Medicina Preventiva y Salud Pública)

Data:	2022
Resum:	Tuberculosis (TB) still represents a major global health problem affecting over 10 million people worldwide. The gold-standard procedures for TB diagnosis are culture and nucleic acid amplification techniques. In this context, both lipoarabinomannan (LAM) urine test and rapid molecular tests have been major game changers. However, the low sensitivity of the former and the cost and the prohibitive infrastructure requirements to scale-up in endemic regions of the latter, make the improvement of the TB diagnostic landscape a priority. Most forms of life produce extracellular vesicles (EVs), including bacteria despite differences in bacterial cell envelope architecture. We demonstrated that Mycobacterium tuberculosis (Mtb), the causative agent of TB, produces EVs in vitro and in vivo as part of a sophisticated mechanism to manipulate host cellular physiology and to evade the host immune system. In a previous serology study, we showed that the recognition of several mycobacterial extracellular vesicles (MEV) associated proteins could have diagnostic properties. In this study, we pursued to expand the capabilities of MEVs in the context of TB diagnostics by analyzing the composition of MEVs isolated from Mtb cultures submitted to iron starvation and, testing their immunogenicity against a new cohort of serum samples derived from TB+ patients, latent TB-infected (LTBI) patients and healthy donors. We found that despite the stringent condition imposed by iron starvation, Mtb reduces the number of MEV associated proteins relative to iron sufficient conditions. In addition, TB serology revealed three new MEV antigens with specific biomarker capacity. These results suggest the feasibility of developing a point-of-care (POC) device based on selected MEV-associated proteins.
Ajuts:	Agencia Estatal de Investigación PID2019-110240RB-I00 Instituto de Salud Carlos III PI19/00666 Instituto de Salud Carlos III FI20/00162
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Mycobacterium tuberculosis ; Extracellular vesicles ; Immunogenicity ; Diagnostic biomarkers ; Serology ; Iron starvation
Publicat a:	Frontiers in microbiology, Vol. 13 (June 2022) , art. 907296, ISSN 1664-302X

DOI: 10.3389/fmicb.2022.907296
PMID: 35814710

13 p, 3.8 MB

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