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Molecular basis for resistance to silver cations in Salmonella

Abstract

Here we report the genetic and proposed molecular basis for silver resistance in pathogenic microorganisms. The silver resistance determinant from a hospital burn ward Salmonella plasmid contains nine open reading frames, arranged in three measured and divergently transcribed RNAs. The resistance determinant encodes a periplasmic silver–specific binding protein (SilE) plus apparently two parallel efflux pumps: one, a P–type ATPase (SilP); the other, a membrane potential–dependent three–polypeptide cation/proton antiporter (SilCBA). The sil determinant is governed by a two–component membrane sensor and transcriptional responder comprising silS and silR, which are co–transcribed. The availability of the sil silver–resistance determinant will be the basis for mechanistic molecular and biochemical studies as well as molecular epidemiology of silver resistance in clinical settings in which silver is used as a biocide.

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Figure 1: Silver resistance determinant, genes, transcripts and protein products.
Figure 2: The metal–binding protein SilE.
Figure 3: Transcript analysis of the silver resistance determinant.
Figure 4: Primer extension analysis of RNA.

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Acknowledgements

We thank A.O. Summers for the plasmid used in this work and for unpublished data, F. Roberto and P. Goodlove for sequencing and analysis, B.–S.B. Lee for N–terminal polypeptide sequencing and advice, and W. Hendrickson, W. Walden, and D.H. Nies for discussions. This work was supported by a grant from the Department of Energy.

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Correspondence to Amit Gupta.

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Gupta, A., Matsui, K., Lo, JF. et al. Molecular basis for resistance to silver cations in Salmonella. Nat Med 5, 183–188 (1999). https://doi.org/10.1038/5545

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