Varela Ramirex, Cristian
(2014).
Metabolism and transport of complex metabolites of mycobacteria.
University of Birmingham.
Ph.D.
Abstract
\(Mycobacterium\) \(tuberculosis\), the causative agent of the infectious disease Tuberculosis, is one of the most successful human pathogen. The disease remains a global health priority due to the spread of HIV and multidrug resistant strains. Therefore, there is a need to extend the understanding of the physiology and pathogenicity of \(M\). \(tuberculosis\) in order to develop new therapies, antimicrobial drugs and vaccines. \(Mycobacterium\) possesses a unique cell envelope responsible for the reduced susceptibility to antibiotics and pathogenicity due to the high lipid content. It is composed by the plasma membrane, an unusual lipid-rich cell wall and an outermost layer known as the capsule. Moreover, other complex metabolites play a role in \(M.\) \(tuberculosis\) virulence such as inorganic polyphosphate, a polymer involved in stringent response and long term survival. In this study, a transposon mutant library was generated in order to identify new genetic determinants related to cell envelope; furthermore, specific mutants strains were generated to investigate the role of MmpL factors in mycolic acids transport, to test the role of a group of ABC-transporters in capsule biosynthesis and also to assess the function of exopolyphosphatases in survival under stress and nutrient limitation condition.
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