| dc.description.abstract | 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 Gramnegative
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. | en |
