Immunogenicity of mycobacterial extracellular vesicles isolated from host-related conditions informs about tuberculosis disease status

ABSTRACT: Tuberculosis (TB) still represents a major global health problem affecting over 10 million people worldwide. At present, there is an urgent need for defining prognostic parameters, differential diagnostic, and correlates of protection from the disease. The gold standard test for TB diagnosis is still smear microscopy, but insufficiently detects pulmonary disease, besides the necessity of having laboratory infrastructures and be time-consuming. Both LAM urine test and Xpert MTB/RIF have been major game changers in this context. However, the low sensitivity of the former and the considerable delay of sample delivery of the latter, make the improvement of the TB diagnostic landscape a priority. The development of rapid point-of-care (POC)-based testing approaches would represent an important breakthrough in TB diagnostics in view of these short-comings. Most forms of life produce extracellular vesicles (EVs) and since the first detection of bacterial EVs more than 60 years, subsequent studies have demonstrated their functional commonality 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, Mtb EVs (MEVs) were used to investigate their potential role as biomarkers to discern between different forms of disease status. It was shown that the recognition of several 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 including TB+, LTBI and healthy donors. We found that MEVs differ in protein composition when Mtb is under host-related stress yet MEVs seem to carry antigens that could serve as bonafide markers for direct detection. In addition, TB serology revealed three new MEV antigens with great biomarker capacity. These results encourage investigating the feasibility of the development of a POC device based on selected MEV-associated proteins.

INSTRUMENT(S): LTQ

ORGANISM(S): Mycobacterium Tuberculosis

DISEASE(S): Tuberculosis

SUBMITTER: Mikel Azkargorta  

LAB HEAD: Felix Elortza

PROVIDER: PXD033170 | Pride | 2022-08-02

REPOSITORIES: Pride