Tuberculosis and diabetes: biomarkers and drug candidates from a host perspective

Author(s):
Doorn, C.L.R. van
Published
2022
Publication type
Doctoral Thesis

Abstract

In this thesis we describe our work regarding the identification of novel biomarkers, host targets and candidate pharmacological compounds for the development of therapies against various intracellular bacterial infections, focusing primarily on the interplay

between tuberculosis and diabetes mellitus. We conducted two longitudinal cohort studies in South Africa and Indonesia, and we applied unbiased and selective transcriptomic approaches to identify novel biomarker profiles in tuberculosis patients with concomitant diabetes or hyperglycaemia. Further, we performed experiments with standardized in vitro cellular infection models for drug discovery. We identified potential host targets during Mycobacterium tuberculosis infections and we describe the role of central metabolic pathways bacterial infections in human macrophages.

Host-directed therapyTuberculosisPrimary human macrophagesSalmonella
Defense date
2022-11-16
Language
English
Supervisor(s)
Ottenhoff, T.H.M.
Advisor(s)
Vianello, E.
Committee member(s)
Geluk, A.; Hoeben, R.C.; Spaink, H.P.; Houben, E.N.G.
Qualification
Ph.D.
Degree granting institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University, Leiden
hdl
1887/3486320

Funding

Sponsorship
the Netherlands Organization for Scientific Research (NWO-TOP Grant Agreement No. 91214038); the NWO-TTW NACTAR grant (Grant Agreement No. 16444); the TANDEM (Tuberculosis and Diabetes Mellitus) Grant of the ECFP7 (European Union’s Seventh Framework Programme) under Grant Agreement No. 305279