Invited Speaker Australian Society for Microbiology Annual Scientific Meeting 2018

Elucidating the Scs redox pathway and its role in copper tolerance in Salmonella (#29)

Pramod Subedi , Jason Paxman , Tony Wang , Ashwinie Ukuwela , Zhiguang Xiao , Begoña Heras

Bacteria use disulfide bond (Dsb) forming enzymes to produce functional virulence factors. In addition to the classic Dsb system, which includes an oxidative DsbA/DsbB pathway and an isomerase DsbC/DsbD pathway, genomic analysis of the human pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), revealed a second Dsb-like system encoded by the scsABCD locus. This Scs locus contains genes encoding for Scs(A-D) proteins that have been associated with an increased tolerance to copper. However, their mechanistic roles in copper transport and homeostasis in Salmonella are still not clearly understood.


To gain a better understanding of the Scs system in S. Typhimurium, we carried out a detailed biochemical and biophysical characterisation of ScsB, an inner membrane protein, and ScsC, a periplasmic soluble protein. The results show that ScsB and ScsC work as a redox pair and form an additional Dsb-like reducing pathway. Furthermore, we have also dissected the molecular mechanism underlying Scs proteins mediated copper tolerance in Salmonella. Our results demonstrate that both ScsB and ScsC, can bind copper (I) with significant affinities and transfer it to the periplasmic copper binding protein, CueP.


Taken together, we show how the Dsb-like Scs system has evolved to protect against copper toxicity by sequestering and transferring copper to periplasmic copper binding proteins. Our findings in S. Typhimurium could have implications on establishing how Gram-negative pathogens that contain similar Dsb-like redox enzymes, deal with the antibacterial action of copper and contribute to bacterial virulence within the host.



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