Doherty, Neil Christopher (2000) A molecular analysis of hyaluronate lyase production in Streptococcus pneumoniae. PhD thesis, University of Warwick.

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Abstract

Streptococcus pneumoniae is a global cause of mortality and morbidity. Its genetic plasticity renders it responsive to the selective pressures of the host environment and antimicrobial chemotherapy.

Hyaluronidase (hyaluronate lyase) is an important protein virulence determinant of this organism, which has previously been described as a spreading factor, facilitating invasion of host tissues during episodes of invasive disease by degrading the hyaluronic acid component of the host extracellular matrix.

The available protein sequence indicates that hyaluronate lyase is exposed to the extracellular environment. Selection to drive variation at the hyl locus by the host immune response was investigated using high-resolution restriction analysis (HRRA) and direct sequence analysis. This revealed that variation of hyl is low, however, there is statistically significant evidence that variation at hyl is mediated by homologous recombination. The low overall divergence suggests that recombination is restricted to the intra-species level.

Phenotypic analysis of hyaluronate lyase activity did not reveal statistically significant associations with site of isolation or genotype. Hyaluronate lyase was shown to be inducible by hyaluronate.

Mutagenesis of the hyl locus reveals that other pneumococcal enzymes do not functionally complement loss of the enzyme.

Hyaluronic acid (HA) is able to support growth of some strains of S. pneumoniae, and hyaluronate lyase has been shown to be required for growth. Pathways for the utilisation of HA derived metabolites are proposed in the light of available pneumococcal genome data, and published observations in other systems.

The previously published hyl gene sequence is thought to be incomplete. Elements upstream of hyl have been isolated and show putative strong promoter and cleavable N-terminal signal sequence.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QH Natural history Q Science > QP Physiology Q Science > QR Microbiology
Library of Congress Subject Headings (LCSH):	Streptococcus pneumoniae -- Analysis, Molecular biology -- Research, Lyases -- Analysis
Official Date:	September 2000
Dates:	Date Event September 2000 Submitted
Institution:	University of Warwick
Theses Department:	Department of Biological Sciences
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Dowson, Chris
Extent:	xvi, 215 leaves : illustrations
Language:	eng

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