Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.700904
Title: Removal of acetylation by pneumococcal esterases potentiates neuraminidase activity for mucin utilisation, colonisation and virulence
Author: Kahya, Hasan Faisal Hussein
ISNI:       0000 0004 5989 4002
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2016
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Abstract:
The genome of pneumococcal strains contains 4 putative esterase genes (SPD_0534, estA; SPD_0932; SPD_1239; and SPD_1506, axe). Esterases have been reported to be important for bacterial physiology and virulence in other microorganisms but their role in S. pneumoniae is unknown. We hypothesised that esterases potentiate neuraminidase activity by removing acetylation in sialic acid. This hypothesis was tested using isogenic mutants and recombinant esterases in microbiological, biochemical and In vivo assays. The results showed that pneumococcal esterases are specific for short acyl chains, all gene contributed to overall esterase activity but SPD_0534 (EstA) was found to be responsible for main esterase activity. Both Axe and EstA could use acetylated xylan and Bovine Sub-maxillary Mucin (BSM), a highly acetylated substrate, but only EstA was active against tributyrin (triglyceride). Incubation of BSM with either Axe or EstA led to the acetate release in a time and concentration dependent manner, and pretreatment of BSM with either EstA or Axe increased sialic acid release by subsequent exposure to neuraminidase. qRT-PCR results showed that the expression level of estA and axe increased when exposed to BSM and in respiratory tissues. Mutation of either estA alone or in combination with nanA (codes for neuraminidase A), or the replacement of serine 121 to alanine in EstA, reduced the pneumococcal ability to utilise BSM as sole carbon source, sialic acid (Sia) release, colonisation and virulence in a mouse model of pneumococcal infection.
Supervisor: Yesilkaya, Hasan ; Andrew, Peter Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.700904  DOI: Not available
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