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Iron and Pseudomonas aeruginosa chronic infection

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O'May, Che Yanon 2008 , 'Iron and Pseudomonas aeruginosa chronic infection', PhD thesis, University of Tasmania.

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Abstract

Pseudomonas aeruginosa forms untreatable infections within the hypoxic mucus of the
cystic fibrosis (CF) lung. This organism persists because it grows as aggregates of
bacteria called biofilms. As iron is essential for bacterial growth, this thesis used in
vitro biofilm models to investigate whether targeting iron with chelators can prevent
and/or help to eradicate P. aeruginosa biofilm growth and therefore be a potential
therapy. Given that P. aeruginosa infections can occur in low-oxygen regions of the CF
lung, assays were conducted under both aerobic and anaerobic atmospheres.
Previous published studies had focused on the standard laboratory strain PAOl under
aerobic conditions. Therefore, the initial part of this thesis characterised biofilm
development by clinical CF isolates, strain PAOl and other non-CF isolates under
aerobic and anaerobic conditions. The CF isolates overall displayed a reduced ability to
form biofilms in short-term biofilm models. In comparison to non-CF isolates, CF
isolates also had slower growth rates, exhibited decreased adherence to glass, and
decreased motilities (swimming, swarming and twitching). These characteristics were
markedly accentuated by anaerobic growth conditions and the findings overall are
consistent with the theory that P. aeruginosa exhibits a biofilm growth mode in the CF
lung. Moreover, the CF strain phenotypes were not readily reversed by culture
manipulations designed to encourage planktonic growth. Incubation of CF isolates in
the longer-term continuous-culture flow-through system, where biofilms were followed
for one week rather than one day, revealed that they exhibited biofilm differentiation
process similar to those reported for strain PAOl. Therefore, results gained from
studies of strain PAOl have clinical relevance. Hence, this strain was used in
subsequent chapters to investigate the effects of iron on biofilm development.
A range of iron-binding compounds impaired biofilm formation under both aerobic
and
anaerobic atmospheres. Chelators were most effective under anaerobic conditions,
~here they completely prevented biofilm development. This impairment correlated
with reducing iron availability. Addition of the iron chelator 2,2' -dipyridyl (2DP) to
mature anaerobic biofilm could cause some eradication of the biofilm and also enhance
the ability of antibiotic tobramycin to kill bacteria within the biofilm.
In conclusion, it is likely that targeting iron will be of clinical benefit in CF individuals.
It will be most beneficial if used early and often to prevent the initial growth and
transformation of P. aeruginosa into a biofilm.

Item Type: Thesis - PhD
Authors/Creators:O'May, Che Yanon
Keywords: Cystic fibrosis, Respiratory organs, Pseudomonas aeruginosa infections
Copyright Holders: The Author
Copyright Information:

Copyright 2008 the author - The University is continuing to endeavour to trace the copyright
owner(s) and in the meantime this item has been reproduced here in good faith. We
would be pleased to hear from the copyright owner(s).

Additional Information:

Available for library use only and copying in accordance with the Copyright Act 1968, as amended. Thesis (PhD)--University of Tasmania, 2008. Includes bibliographical references

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