The copper supply pathway to a Salmonella Cu, Zn‐superoxide dismutase (SodCII) involves P1B‐type ATPase copper efflux and periplasmic CueP. Issue 3 (11th December 2012)

• Record Type: Journal Article
• Authors: Osman, Deenah; Patterson, Carl J.; Bailey, Kathryn; Fisher, Karl; Robinson, Nigel J.; Rigby, Stephen E. J.; Cavet, Jennifer S.
• Is Part Of: Molecular microbiology. Volume 87:Issue 3(2013)
• Page Start: 466
• Page End: 477
• Publication Date: 2012-12-11
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.12107
• Languages: English
• ISSNs: 0950-382X

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>Periplasmic Cu, Zn‐superoxide dismutases (Cu, Zn‐SODs) are implicated in bacterial virulence. It has been proposed that some bacterial P<sub>1</sub><sub>B</sub>‐type ATPases supply copper to periplasmic cupro‐proteins and such transporters have also been implicated in virulence. Here we show that either of two P<sub>1</sub><sub>B</sub>‐type ATPases, CopA or GolT, is needed to activate a periplasmic Cu, Zn‐SOD (SodCII) in <italic>Salmonella enterica</italic> serovar Typhimurium. A Δ<italic>copA</italic>/Δ<italic>golT</italic> mutant accumulates inactive Zn‐SodCII which can be activated by copper‐supplementation <italic>in vitro</italic>. In contrast, either single ATPase mutant accumulates fully active Cu, Zn‐SodCII. A contribution of GolT to copper handling is consistent with its copper‐responsive transcription mediated by DNA‐binding metal‐responsive activator GolS. The requirement for duplicate transcriptional activators CueR and GolS remains unclear since both have similar tight <italic>K</italic><sub>Cu</sub>. Mutants lacking periplasmic cupro‐protein CueP also accumulate inactive Zn‐SodCII and while CopA and GolT show functional redundancy, both require CueP to activate SodCII <italic>in vivo</italic>. Zn‐SodCII is also activated <italic>in vitro</italic> by incubation with Cu‐CueP and this coincides with copper transfer as monitored by electron paramagnetic resonance spectroscopy. These experiments establish a role for CueP within the copper supply pathway for <italic>Salmonella</italic> Cu, Zn‐SodCII. Copper binding by CueP in this pathogen may confer protection of the periplasm from copper‐mediated damage while sustaining vital cupro‐enzyme activity.</p> </abstract>