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Infection and Immunity, April 2000, p. 1834-1839, Vol. 68, No. 4
New Product Research Laboratories I, Daiichi
Pharmaceutical Co., Ltd., Tokyo 134-8630, Japan
Received 11 October 1999/Returned for modification 29 November
1999/Accepted 3 January 2000
Pseudomonas aeruginosa produces siderophores, pyoverdin
and pyochelin, for high-affinity iron uptake. To investigate their contribution to P. aeruginosa infections, we constructed
allelic exchange mutants from strain PAO1 which were deficient in
producing one or both of the siderophores. When inoculated into the
calf muscles of immunosuppressed mice, pyochelin-deficient and
pyoverdin-deficient mutants grew and killed the animals as efficiently
as PAO1. In contrast, the pyochelin- and pyoverdin-deficient (double)
mutant did not show lethal virulence, although it did infect the
muscles. On the other hand, when inoculated intranasally, all mutants
grew in the lungs and killed immunosuppressed mice. Compared with PAO1, however, the pyoverdin-deficient mutant and the double mutant grew
poorly in the lungs, and the latter was significantly attenuated for
virulence. Irrespective of the inoculation route, the
pyoverdin-deficient and doubly deficient mutants detected in the blood
were significantly less numerous than PAO1. Additionally, in vitro
examination demonstrated that the growth of the double mutant was
extremely reduced under a free-iron-restricted condition with
apotransferrin but that the growth reduction was completely canceled by
supplementation with hemoglobin as a heme source. These results suggest
that both pyoverdin and pyochelin are required for efficient bacterial
growth and full expression of virulence in P. aeruginosa
infection, although pyoverdin may be comparatively more important for
bacterial growth and dissemination. However, the siderophores were not
always required for infection. It is possible that
non-siderophore-mediated iron acquisition, such as via heme uptake,
might also play an important role in P. aeruginosa infections.
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Impact of Siderophore Production on
Pseudomonas aeruginosa Infections in Immunosuppressed
Mice
*
Corresponding author. Mailing address: New Product
Research Laboratories I, Daiichi Pharmaceutical Co., Ltd. 16-13, Kita-Kasai 1-chome, Edogawa-ku, Tokyo 134-8630, Japan. Phone:
81-3-3680-0151. Fax: 81-3-5696-8344. E-mail:
takas4px{at}daiichipharm.co.jp.
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