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Tuberculosis causes more deaths globally, and in China, than any other single pathogen. Some of the reasons for its success are the ability of the causative organism, Mycobacterium tuberculosis, to lie undetected in the host for decades (clinical latency), the very long treatment times for successful antibiotic treatment (phenotypic resistance) and emerging drug resistance to effective antibiotics. The Javid laboratory is interested in investigating some of the fundamental physiological mycobacterial processes that may contribute to these phenotypes.
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We have previously shown that the protein translation error rate (mistranslation rate) in mycobacteria is unusually high. Importantly, manipulation of the error rate, both up and down, appears to have profound effects on antibiotic phenotypic resistance. We have shown that mycobacterial strains with high error rates have remarkable phenotypic resistance to the antibiotic rifampicin, and the opposite is true for high fidelity mutants. We are interested in investigating the basic mechanism for these observations, and identifying other potentially adaptive phenotypes that arise from low translational fidelity.
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Mycobacteria
host-pathogen
interactions
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The majority of people infected with M. tuberculosis – almost a third of the world’s population – do not become ill unless their immune system weakens. This suggests that mycobacteria have evolved to evade host immune responses, much like other chronic infections. We are interested in investigating the mechanisms by which mycobacteria manipulate the host environment to their own ends. We use a variety of approaches – including proteomic profiling of mycobacteria-infected cells, flow cytometry and forward genetics to address these questions.
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