JAC Advance Access published online on November 1, 2002
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkf209
© 2002 by The British Society for Antimicrobial Chemotherapy
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Original Paper
1 Department of Microbiology
Eastman Dental Institute
for Oral Health Care Sciences, University College London, 256 Gray's
Inn Road, London WC1X 8LD, UK; Department of Cellular Microbiology
Research Group, Eastman Dental Institute
for Oral Health Care Sciences, University College London, 256 Gray's
Inn Road, London WC1X 8LD, UK
* Corresponding author. E-mail: M.Wilson{at}eastman.ucl.ac.uk.
Received 6 February 2002
; revised 20 August 2002
Objectives. The growing resistance
of methicillin-resistant Staphylococcus aureus (MRSA)
to conventional antimicrobial agents necessitates the development
of alternative approaches to preventing and treating infections.
One such approach is photodynamic therapy, whereby target cells
are treated with light-activated drugs (photosensitizers). This
investigation aimed to determine whether the ability of MRSA to
express the IgG-binding protein, protein A, could be exploited to
enable selective lethal photosensitization of the organism with
a photosensitizer [tin (IV) chlorin e6; SnCe6] linked
to IgG. Methods. Various strains of MRSA were exposed
to light from a helium/neon laser in the presence of an IgG-SnCe6
conjugate and the survivors enumerated by viable counting. Controls
consisted of suspensions irradiated in the presence or absence of
the conjugate and suspensions kept in the dark in the presence of
the conjugate. Similar experiments were also carried out using the
unconjugated photosensitizer. The experiments were repeated using
a suspension consisting of both EMRSA-16 and Streptococcus
sanguis. Results. EMRSA-16 was killed by IgG-SnCe6
and SnCe6 in a light-dose- and photosensitizer-dependent manner.
Greater kills were achieved with the IgG-SnCe6 than with
the unconjugated SnCe6 using the same light energy dose and photosensitizer
concentration. Furthermore, the IgG-SnCe6 conjugate, but
not SnCe6, was able to kill EMRSA-16 selectively in a suspension
that also contained S. sanguis without any reduction
in the viable count of the latter. Conclusion. These results demonstrate that selective
lethal photosensitization of MRSA can be achieved using an IgG-tin
(IV) chlorin e6 conjugate. The effectiveness of killing was dependent, in
part, on the particular MRSA strain used, with the clinically important
EMRSA-16 strain being the most susceptible.
Keywords: MRSA, tin (IV) chlorin e6, IgG-binding protein
A
Selective lethal photosensitization of methicillin-resistant
Staphylococcus aureus using an IgG-tin (IV) chlorin
e6 conjugate
2 Department of Cellular Microbiology
Research Group, Eastman Dental Institute
for Oral Health Care Sciences, University College London, 256 Gray's
Inn Road, London WC1X 8LD, UK
3 Laboratory
of Hospital Infection, Central Public Health Laboratory, Colindale,
London, UK
4 Department of Microbiology
Eastman Dental Institute
for Oral Health Care Sciences, University College London, 256 Gray's
Inn Road, London WC1X 8LD, UK
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