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Title: Study of the range of antibody levels and activities of Acinetobacter calcoaceticus-Acinetobacter baumannii complex and Haemophilus influenzae lipopolysaccharides
Author: Morgan, Robert Frederick Somerset
ISNI:       0000 0004 2730 9665
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2009
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Hospital acquired pneumonia is a major problem in the nosocomial environment worldwide. The rise in the number and level of antibiotic resistant strains of bacteria means that conventional therapies are no longer as effective as they once were. Many of the main causative organisms are Gram-negative rods, such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Haemophilus influenzae and one that has become a greater problem in the last twenty years Acinetobacter genospecies 13 TU. Lipopolysaccharide (LPS) is a molecule that is found on the cell surface of all Gram-negative organisms. LPS is a vital part of the outer membrane of Gram-negative bacteria and is a major factor in these organisms’ ability to cause serious infection and disease. While many Gram-negative organisms, such as E. coli and Klebsiella pneumoniae, are well characterised, other species that have become potential nosocomial pathogens more recently, such as Acinetobacter genospecies 13 TU, are much less well characterised. It is unknown as to how widespread exposure to Acinetobacter genospecies 13 TU is in a healthy population. Also, little is also about pathogenesis of Acinetobacter genospecies 13 TU such as the capacity for induction of cytokines by the Acinetobacter genospecies 13 TU LPS LPS was extracted with the aqueous phenol method and re-purified by Voegel’s method from eight strains of Acinetobacter genospecies 13 TU, four strains of Haemophilus influenzae, two strains of Pseudomonas aeruginosa, two strains of Klebsiella pneumoniae and two strains of E. coli. These LPSs were used in enzyme linked immunosorbant assays (ELISAs) with serum taken from 475 blood donors from the Southeast Scotland Blood Transfusion Service. The results from the ELISAs were averaged for each individual blood donor across all the species tested. These averaged results were compared across the species. LPS from two strains of each species, ten in all, were used to challenge the THP-1 human monocytic cell line and the mRNA was extracted and used in quantitative polymerase chain reactions to measure cytokine induction. It was seen that exposure to Acinetobacter genospecies 13 TU LPS is about as widespread in a healthy population from Southeast Scotland as exposure to Pseudomonas aeruginosa LPS and somewhat similar to Klebsiella pneumoniae LPS. Antibodies to E. coli LPS and Haemophilus influenzae LPS were similarly widespread in a healthy population from Southeast Scotland. These last two were much more widely spread than the other organisms tested. Some individuals seem to produce antibodies at high levels to all of the LPSs tested. It may be possible to use serum from these individuals to make a hyper-immune immunoglobulin preparation to be used in the immunotherapy of hospital associated pneumonia. The LPS from one of the strains of Acinetobacter genospecies 13 TU was able to induce similar levels of cytokine production as Klebsiella pneumoniae and Pseudomonas aeruginosa. It was able to induce higher levels of cytokine production over a greater number of cytokines than both Haemophilus influenzae and E. coli LPS. LPS from the other strain of Acinetobacter genospecies 13 TU tested induced lower levels of cytokines compared to the other strain. These levels were lower than those developed by Haemophilus influenzae and E. coli LPS as well as those induced by the LPSs from Klebsiella pneumoniae and Pseudomonas aeruginosa. It seems that there is a range of different levels of cytokine production induced by Acinetobacter genospecies 13 TU LPS with some strains inducing high levels and others inducing low levels of cytokines.
Supervisor: Poxton, Ian. ; Simpson, John. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Lipopolysaccharide ; Acinetobacter ; acinetobacter calcoaceticus-acinetobacter baumanni complex ; antibodies