Cargando…

Immunogenicity of Mycobacterial Extracellular Vesicles Isolated From Host-Related Conditions Informs About Tuberculosis Disease Status

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 be...

Descripción completa

Detalles Bibliográficos
Autores principales: Schirmer, Sebastian, Rauh, Lucas, Alebouyeh, Sogol, Delgado-Velandia, Mario, Salgueiro, Vivian C., Lerma, Laura, Serrano-Mestre, José L., Azkargorta, Mikel, Elortza, Félix, Lavín, José L., García, Maria Jesus, Tórtola Fernández, María Teresa, Gola, Susanne, Prados-Rosales, Rafael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257102/
https://www.ncbi.nlm.nih.gov/pubmed/35814710
http://dx.doi.org/10.3389/fmicb.2022.907296
_version_ 1784741265520197632
author Schirmer, Sebastian
Rauh, Lucas
Alebouyeh, Sogol
Delgado-Velandia, Mario
Salgueiro, Vivian C.
Lerma, Laura
Serrano-Mestre, José L.
Azkargorta, Mikel
Elortza, Félix
Lavín, José L.
García, Maria Jesus
Tórtola Fernández, María Teresa
Gola, Susanne
Prados-Rosales, Rafael
author_facet Schirmer, Sebastian
Rauh, Lucas
Alebouyeh, Sogol
Delgado-Velandia, Mario
Salgueiro, Vivian C.
Lerma, Laura
Serrano-Mestre, José L.
Azkargorta, Mikel
Elortza, Félix
Lavín, José L.
García, Maria Jesus
Tórtola Fernández, María Teresa
Gola, Susanne
Prados-Rosales, Rafael
author_sort Schirmer, Sebastian
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9257102
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-92571022022-07-07 Immunogenicity of Mycobacterial Extracellular Vesicles Isolated From Host-Related Conditions Informs About Tuberculosis Disease Status Schirmer, Sebastian Rauh, Lucas Alebouyeh, Sogol Delgado-Velandia, Mario Salgueiro, Vivian C. Lerma, Laura Serrano-Mestre, José L. Azkargorta, Mikel Elortza, Félix Lavín, José L. García, Maria Jesus Tórtola Fernández, María Teresa Gola, Susanne Prados-Rosales, Rafael Front Microbiol Microbiology 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. Frontiers Media S.A. 2022-06-22 /pmc/articles/PMC9257102/ /pubmed/35814710 http://dx.doi.org/10.3389/fmicb.2022.907296 Text en Copyright © 2022 Schirmer, Rauh, Alebouyeh, Delgado-Velandia, Salgueiro, Lerma, Serrano-Mestre, Azkargorta, Elortza, Lavín, García, Tórtola Fernández, Gola and Prados-Rosales. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Schirmer, Sebastian
Rauh, Lucas
Alebouyeh, Sogol
Delgado-Velandia, Mario
Salgueiro, Vivian C.
Lerma, Laura
Serrano-Mestre, José L.
Azkargorta, Mikel
Elortza, Félix
Lavín, José L.
García, Maria Jesus
Tórtola Fernández, María Teresa
Gola, Susanne
Prados-Rosales, Rafael
Immunogenicity of Mycobacterial Extracellular Vesicles Isolated From Host-Related Conditions Informs About Tuberculosis Disease Status
title Immunogenicity of Mycobacterial Extracellular Vesicles Isolated From Host-Related Conditions Informs About Tuberculosis Disease Status
title_full Immunogenicity of Mycobacterial Extracellular Vesicles Isolated From Host-Related Conditions Informs About Tuberculosis Disease Status
title_fullStr Immunogenicity of Mycobacterial Extracellular Vesicles Isolated From Host-Related Conditions Informs About Tuberculosis Disease Status
title_full_unstemmed Immunogenicity of Mycobacterial Extracellular Vesicles Isolated From Host-Related Conditions Informs About Tuberculosis Disease Status
title_short Immunogenicity of Mycobacterial Extracellular Vesicles Isolated From Host-Related Conditions Informs About Tuberculosis Disease Status
title_sort immunogenicity of mycobacterial extracellular vesicles isolated from host-related conditions informs about tuberculosis disease status
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257102/
https://www.ncbi.nlm.nih.gov/pubmed/35814710
http://dx.doi.org/10.3389/fmicb.2022.907296
work_keys_str_mv AT schirmersebastian immunogenicityofmycobacterialextracellularvesiclesisolatedfromhostrelatedconditionsinformsabouttuberculosisdiseasestatus
AT rauhlucas immunogenicityofmycobacterialextracellularvesiclesisolatedfromhostrelatedconditionsinformsabouttuberculosisdiseasestatus
AT alebouyehsogol immunogenicityofmycobacterialextracellularvesiclesisolatedfromhostrelatedconditionsinformsabouttuberculosisdiseasestatus
AT delgadovelandiamario immunogenicityofmycobacterialextracellularvesiclesisolatedfromhostrelatedconditionsinformsabouttuberculosisdiseasestatus
AT salgueirovivianc immunogenicityofmycobacterialextracellularvesiclesisolatedfromhostrelatedconditionsinformsabouttuberculosisdiseasestatus
AT lermalaura immunogenicityofmycobacterialextracellularvesiclesisolatedfromhostrelatedconditionsinformsabouttuberculosisdiseasestatus
AT serranomestrejosel immunogenicityofmycobacterialextracellularvesiclesisolatedfromhostrelatedconditionsinformsabouttuberculosisdiseasestatus
AT azkargortamikel immunogenicityofmycobacterialextracellularvesiclesisolatedfromhostrelatedconditionsinformsabouttuberculosisdiseasestatus
AT elortzafelix immunogenicityofmycobacterialextracellularvesiclesisolatedfromhostrelatedconditionsinformsabouttuberculosisdiseasestatus
AT lavinjosel immunogenicityofmycobacterialextracellularvesiclesisolatedfromhostrelatedconditionsinformsabouttuberculosisdiseasestatus
AT garciamariajesus immunogenicityofmycobacterialextracellularvesiclesisolatedfromhostrelatedconditionsinformsabouttuberculosisdiseasestatus
AT tortolafernandezmariateresa immunogenicityofmycobacterialextracellularvesiclesisolatedfromhostrelatedconditionsinformsabouttuberculosisdiseasestatus
AT golasusanne immunogenicityofmycobacterialextracellularvesiclesisolatedfromhostrelatedconditionsinformsabouttuberculosisdiseasestatus
AT pradosrosalesrafael immunogenicityofmycobacterialextracellularvesiclesisolatedfromhostrelatedconditionsinformsabouttuberculosisdiseasestatus