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Steroid metabolism in Actinomycetales and the relation to pathogenicity

Kok, N.A.W de (2014) Steroid metabolism in Actinomycetales and the relation to pathogenicity. Bachelor's Thesis, Biology.

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Steroids are group of molecules with a specific 4-ring structure which are found in Eukaryotic organisms. Steroids have various functions; they can be hormonal compounds, but can also, for example, modulate cell wall fluidity/rigidity. The order of Actinomycetales is known to contain species of bacteria which thrive in a broad range of environments. Due to this property the species within this order have developed the ability to degrade a variety of organic compounds, including m-toluate, polycyclic aromatic hydrocarbons and polychlorinated biphenyls and steroids. Mycobacterium tuberculosis is the causative agent of tuberculosis worldwide and is known to be able to catabolize cholesterol, a steroid. M. tuberculosis infects an estimated third of the world population and causes three million deaths annually, making it a very successful human pathogen. The hallmark property of M. tuberculosis is its ability to cause a persistent lung infection involving multiplication inside phagosomes of alveolar macrophages following phagocytosis. Multiple studies have shown that various genes which are implicated in cholesterol catabolism are also essential to establishing persistent infection in murine models. These findings suggest that cholesterol catabolism is required for persistent infection. Although, it remains unknown how cholesterol catabolism plays a role in in vivo infection models it is tempting to speculate that M. tuberculosis requires cholesterol as a carbon and energy source during survival and growth in the macrophage phagosome. In this work various genes which are known to be implicated in cholesterol catabolism and pathogenicity in various actinomycetales are reviewed and discussed. From the conducted research it seems that there are multiple factors accounting for the pathogenicity of M. tuberculosis. The mycobacterial cell wall contains mannosylated lipoarabinomannan, which is likely the main factor responsible for inhibition of maturation of the phagosome. Suspectedly it prevents the fusion of the phagosome with lysosomes which would otherwise form a phagolysosome. Additionally, the findings include that the production of a diterpenoid seems to assist in prevention of acidification of the phagosome. Moreover, a deletion of genes implicated in cholesterol metabolism (e.g.: mce4, kshA, kshB, igr, kstD and hsaABCD) seems to abolish the ability of M. tuberculosis to develop a persistent infection. Nevertheless, this does not seem to be true for the deletion of hsd (cholesterol oxidase), as hsd does! not seem to be required for growth in macrophages. This leads to the conclusion that multiple virulence factors account for the pathogenicity of M. tuberculosis and related bacteria. Furthermore, the utilization of cholesterol in M. tuberculosis is still not fully understood and this merits further research which would be of interest to the biotechnological and pharmaceutical industries.

Item Type: Thesis (Bachelor's Thesis)
Degree programme: Biology
Thesis type: Bachelor's Thesis
Language: English
Date Deposited: 15 Feb 2018 08:02
Last Modified: 15 Feb 2018 08:02

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