Cumley, Nicola
(2012).
The molecular basis for virulence in Streptococcus Agalactiae.
University of Birmingham.
Ph.D.
Abstract
Group B Streptococcus (GBS) is a leading cause of neonatal meningitis and septicaemia. During the progression of invasive disease, GBS must be able to detect and adapt to a diverse range of environments. One of the challenging environments the organisms will encounter is the antimicrobial phagosome of cells of the innate immune system. Combining microscopy with pharmaceutical approaches, I have been able to show that GBS is residing within a vacuole that acquires phagolysosomal markers and, that acidification of the phagosome is required for GBS to survive. In addition this work has demonstrated that GBS induces only a weak reactive oxygen burst in macrophages and consequently reactive oxygen species are of limited importance. Interestingly, however, the GBS acid response regulator CovS/R is crucial for the organism’s ability to survive within murine macrophages. This is most likely due to the regulation of genes required for adaption to the intracellular environment.Lastly, to facilitate investigations into the interaction of GBS with the phagosome it would be desirable to be able to visualise live organisms within cells. In the final part of this thesis, I describe an evaluation of different approaches to generate a suitable, fluorescently labelled, strain of GBS.
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