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Lung infections in cystic fibrosis patients are often particularly difficult to treat. This is partly because of resistance to many broad-spectrum antimicrobials and partly because of the ability of these bacteria to form biofilms in vivo which retards penetration of the antimicrobial agent.1
This project aims to improve the properties of the antibiotic ciprofloxacin to overcome these problems by conjugating it to siderophores, which are ligands that bacteria use to take essential iron into the cell. The antimicrobial is hence taken up along with the siderophore and actively concentrated inside the cell (Trojan horse strategy). This conjugate formation improves activity and can overcome bacterial resistance arising from changes to cell permeability and drug efflux.
Individual objectives are:
(1) To synthesise siderophore-ciprofloxacin conjugates based on carboxylate-type siderophores.
(2) To characterise the conjugates thus obtained and to investigate their iron binding properties.
(3) To investigate gallium, which resembles iron, as an alternative metal.
(4) Within a collaborative programme, to participate in the testing of the efficacy of the Fe(III)- and Ga(III)-complexes of the conjugates for antimicrobial and biofilm inhibiting activity using a similar panel of reference and clinical strains as in our earlier work.2
The project involves synthetic chemistry, organic chemistry, coordination chemistry and provides the opportunity to gain expertise in basic microbiology.
Funding Notes:
Competition funding for a Teaching Studentship or Research Council Funding to start on 1 October 2012 open to UK and EU applicants. The first round of applications has now closed but if funding is not allocated at the end of February, a second round of awards will be made in April. Overseas Applicants may apply if they are able to SELF FUND THEIR OWN STUDIES.
References:
1 Hoiby, N. Recent advances in the treatment of Pseudomonas aeruginosa infections in cystic fibrosis, BMC Medicine, 2011, 9, 32.
2 S. R. Md-Saleh, E. C. Chilvers, K. G. Kerr, S. J. Milner, A. M. Snelling, J. P. Weber, G. H. Thomas, A.-K. Duhme-Klair, A. Routledge, Bioorg. Med. Chem. Lett., 2009, 19, 1496.
Research Assessment Exercise (RAE) 2008 Results