Dataset Information

Protein composition of circulating exosomes depend on tuberculosis disease state

ABSTRACT: Tuberculosis (TB) is a contagious disease that is a primary cause of mortality and illness in around a quater of the world' population particular in low income nations. The disease most commonly affects lung, but pathogens can also be found in other parts of the body. Mycobacterium tuberculosis (Mtb) is the etiologic agent of TB and its ability to penetrate immune cells and develop a niche by beating the host's defense mechanism is crucial to its pathogenic sucess. Mtb has a diverse lipid and protein spectrum. Understanding the host-pathogen-interplay in active TB will have a substantial impact in understanding molecular mechanisms of Mtb infection and guide the development of vaccination, diagnostics and therapy response monitoring.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human) Mycobacterium Tuberculosis

TISSUE(S): Blood Plasma

DISEASE(S): Lymph Node Tuberculosis,Pulmonary Tuberculosis,Extrapulmonary Tuberculosis

SUBMITTER: Johannes Schmidt

LAB HEAD: Prof. Dr. Stefan Kalkhof

PROVIDER: PXD030883 | Pride | 2022-05-20

REPOSITORIES: Pride

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Publications

Mycobacterium tuberculosis Affects Protein and Lipid Content of Circulating Exosomes in Infected Patients Depending on Tuberculosis Disease State.

Biadglegne Fantahun F Schmidt Johannes R JR Engel Kathrin M KM Lehmann Jörg J Lehmann Robert T RT Reinert Anja A König Brigitte B Schiller Jürgen J Kalkhof Stefan S Sack Ulrich U

Biomedicines 20220327 4

Tuberculosis (TB), which is caused by the bacterium Mycobacterium tuberculosis (Mtb), is still one of the deadliest infectious diseases. Understanding how the host and pathogen interact in active TB will have a significant impact on global TB control efforts. Exosomes are increasingly recognized as a means of cell-to-cell contact and exchange of soluble mediators. In the case of TB, exosomes are released from the bacillus and infected cells. In the present study, a comprehensive li ...[more]

PMID: 35453532

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Project description: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.

Dataset Information

Protein composition of circulating exosomes depend on tuberculosis disease state

Publications

<i>Mycobacterium tuberculosis</i> Affects Protein and Lipid Content of Circulating Exosomes in Infected Patients Depending on Tuberculosis Disease State.

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