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

Doorn, C.L.R. van (2022)

Doctoral Thesis

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 therapy
• Tuberculosis
• Primary human macrophages
• Salmonella

• All authors: Doorn, C.L.R. van
• Supervisor: Ottenhoff, T.H.M.
• Co-supervisor: Vianello, E.
• Committee: Geluk, A.; Hoeben, R.C.; Spaink, H.P.; Houben, E.N.G.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2022-11-16
• 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