Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.739973
Title: Functional characterisation of TprA/PhrA quorum sensing system in Streptococcus pneumoniae
Author: Motib, Anfal Shakir
ISNI:       0000 0004 7231 915X
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2018
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Abstract:
Quorum-sensing (QS) mechanisms are pivotal for microbial adaptation to host environments, and often required for pathogenesis without affecting bacterial vitality. Hence targeting QS diminish the fitness cost of inhibition, and the emergence and spread of antibiotic resistance. I characterized the TprA/PhrA QS system in the important human pathogen Streptococcus pneumoniae with a view to target its operation using novel soluble linear molecularly imprinted polymers (LMIP). I found that TprA/PhrA system is commonly found in pneumococcal strains, and is required for mucin, galactose and mannose utilisation. On galactose, TprA is an activator of the virulence determinant neuraminidase (nanA), and controls the expression of nine different operons on galactose and mannose. tprA and phrA mutants are highly attenuated in the mouse model of pneumonia and septicemia, and in the chinchilla model of otitis media, indicating that the TprA/PhrA system is a major virulence determinant and a highly relevant anti-infective target. To interfere with the operation of TprA/PhrA, I used, for the first time, highly homogenous soluble LMIP specific to the PhrA peptide. LMIP decreased PhrA-induction in a dose-dependent and sequence-specific manner, and possessed no visible toxicity in the murine model. It was also shown that LMIP were protective against lethal pneumococcal challenge. This study sets the stage for studies on a novel class of drugs to target Gram positive pathogens.
Supervisor: Yesilkaya, Hasan ; Andrew, Peter Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.739973  DOI: Not available
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