Tuberculosis is one of the deadliest infections causing close to 10 million infections and 1.5 million deaths yearly according to estimates by WHO (2015). Tuberculosis is a persistent and potentially lethal infection that is rarely eradicated by the immune system and reacts slowly to antibiotic treatment. In general, a combination of 4 drugs is prescribed for a minimum of six months. The prolonged treatment strategy has led to poor treatment compliance and the subsequent development of multi-drug resistant strains of Mycobacterium tuberculosis. The current vaccine against tuberculosis has limited efficacy and new treatment strategies are urgently needed to be able to control the global tuberculosis burden.
Group Parikka is interested in studying the mechanisms behind mycobacterial persistence both in the context of evading the host immune responses as well as phenotypic tolerance to antibiotic treatment. We utilize the Mycobacterium marinum-zebrafish model to better understand the complex interplay between pathogenic mycobacteria and the host organism. Despite the evolutionary distance between fish and man, this model has proven to mimic the pathogenesis of human tuberculosis and has already lead to major advances in understanding the human disease.
Our current research projects focus on
1) the optimal immune response to eradicate mycobacteria upon infection
2) the role of microbial community life-style and biofilm formation in mycobacterial pathogenesis and phenotypic tolerance to antibiotic treatment
3) using the zebrafish-M.marinum model to study the efficacy of new antimycobacterial drugs
We utilize a wide array of methods ranging from microbiology, quantitative PCR, histology, flow-cytometry to confocal microscopy. We also have a selection of fluorescent mycobacterial strains and zebrafish lines that allow us to study the progression of the disease in detail in vivo and ex vivo, even at the level of single bacterial lesions known as granulomas. Mutant mycobacteria and zebrafish can also be used in these applications.