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Naji, M. |
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Motta, Antonella |
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Aletan, Dirar |
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Mohamed, Tarek |
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Ertürk, Emre |
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Taccardi, Nicola |
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Kononenko, Denys |
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Petrov, R. H. | Madrid |
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Alshaaer, Mazen | Brussels |
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Bih, L. |
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Casati, R. |
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Muller, Hermance |
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Kočí, Jan | Prague |
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Šuljagić, Marija |
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Kalteremidou, Kalliopi-Artemi | Brussels |
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Azam, Siraj |
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Ospanova, Alyiya |
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Blanpain, Bart |
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Ali, M. A. |
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Popa, V. |
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Rančić, M. |
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Ollier, Nadège |
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Azevedo, Nuno Monteiro |
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Landes, Michael |
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Rignanese, Gian-Marco |
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Leys, Natalie
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document
DISSECTION OF A NOVEL METAL RESISTANCE MECHANISM IN CUPRIAVIDUS METALLIDURANS
Abstract
Cupriavidus metallidurans strains contain many genes involved in the resistance and processing of heavy<br/>metals, which are very well studied and characterized. In addition, studies at SCK•CEN underscored the<br/>rapid evolution of C. metallidurans strains towards significantly increased metal resistance, particularly for<br/>silver. Our objective is to understand the molecular mechanisms of this increased resistance to silver.<br/>C. metallidurans strains including type strain CH34, its plasmidless derivatives AE104 and NA4, isolated<br/>from a silver-sanitized drinking water system, were grown in toxic levels of silver to obtain silver-resistant<br/>mutants. The latter were characterized in detail via re-sequencing, oligonucleotide microarrays, RNA-seq<br/>and deletion and complementation analyses.<br/>Our data indicate that C. metallidurans is able to adapt rapidly to toxic silver concentrations. Silver-resistant<br/>mutants were obtained from different strains, even from strains cured from the main mega-plasmid encoded<br/>metal resistance determinants, indicating that the canonical efflux mechanisms are not involved. Wholegenome<br/>expression profiling in non-selective growth conditions showed that only a few genes are commonly<br/>up-regulated in all obtained silver-resistant mutants and some of them are downregulated in the absence of<br/>a two-component system. In addition, deletion mutants and plasmid-based complementation confirmed that<br/>a two-component regulatory system and two genes coding for small periplasmic proteins play a central role.<br/>These results represent a previously uncharacterized molecular mechanism for metal/silver resistance.