dc.contributor.author | Shaw, Deborah | en |
dc.date.accessioned | 2018-01-31T11:37:16Z | |
dc.date.available | 2018-01-31T11:37:16Z | |
dc.date.issued | 1996 | |
dc.identifier.uri | http://hdl.handle.net/1842/27370 | |
dc.description.abstract | | en |
dc.description.abstract | Burkholderia cepacia is an aerobic Gram- negative bacterium originally described as
the cause of soft rot in onions but now recognised as a serious human pathogen most
notably in patients with cystic fibrosis (CF), the most common, fatal inherited disease
affecting Caucasian populations. Bacteroides fragilis, a Gram- negative commensal
associated with the mucosal surface of the human colon, is the most frequently
isolated anaerobic bacterium from clinical specimens and is increasingly implicated as
an important source of endotoxin in gut-derived sepsis. Previously, both organisms
were considered to pose little hazard to human health and consequently, their
pathogenesis and virulence factors are poorly understood. The cell surface
components of a bacterium are classic virulence determinants and the influence of
growth environment on the plasticity of the bacterial surface is well -established. This
thesis considers the environmental regulation and biological activity of putative
virulence factors for both organisms. | en |
dc.description.abstract | Initial studies focused on the expression and antigenicity of the cell surface
components; lipopolysaccharide (LPS), exopolysaccharide (EPS) and outer membrane
from several representative strains. To determine the influence of growth
environment, these components were investigated under different culture conditions
and extraction methods. Results demonstrated that as with other Gram- negative
organisms, the composition of outer membrane proteins of both B. cepacia and
B. fragilis were influenced by cultural conditions with bacteria inducing or repressing
protein structures presumably to influence overall permeability and survival. The EPS
and LPS of B. fragilis also varied with environmental growth condition.
Interestingly, extraction method was found to influence the LPS structure of
B. cepacia including the loss of the distinctive rough LPS phenotype of an 'epidemic'
strain. | en |
dc.description.abstract | B. cepacia and B. fragilis exhibited a greater biological activity than previously
recognised both in terms of endotoxicity and cytokine induction. For B. cepacia the
capacity to induce the proinflammatory cytokines TNF -a and IL -8 from several cell
types was significantly, and unexpectedly, higher compared to the other major CF
pathogen, Pseudomonas aeruginosa. This enhanced inflammatory potential of
B. cepacia was not due to a more efficient LPS signalling pathway. As both CF
pathogens appeared to induce TNF -a in a similar manner, the combined effect of
both species was examined. Surprisingly, when P. aeruginosa was present in
increasing amounts compared to B. cepacia, cytokine levels were down -regulated.
These results indicate that B. cepacia has a major potential to cause immune - mediated damage and concurrent colonisation with P. aeruginosa may modulate this
effect. For B. fragilis cytokine levels were compared to Escherichia coli, a
facultative anaerobic commensal considered of great importance in gut- derived
sepsis due to its extremely active LPS. TNF -a levels induced by B. fragilis were
20 -fold lower than E. coli. However, considering the predominance of Bacteroides
species in the gut, outnumbering facultative organisms by 20 -300 fold, results imply
that as a population B. fragilis may possess as much biological potential as E. coli.
Thus, B. fragilis may play a vital role in gut- derived sepsis. The relevance of these
findings to the understanding of B. cepacia in CF and of B. fragilis in sepsis is
discussed. | en |
dc.publisher | The University of Edinburgh | en |
dc.relation.ispartof | Annexe Thesis Digitisation Project 2017 Block 16 | en |
dc.relation.isreferencedby | Already catalogued | en |
dc.title | The regulation and biological activity of cell surface virulence determinants in model opportunist aerobic and anaerobic bacterial pathogens | en |
dc.type | Thesis or Dissertation | en |
dc.type.qualificationlevel | | en |
dc.type.qualificationname | PhD Doctor of Philosophy | en |