Evolution and diversity of periplasmic proteins involved in copper homeostasis in gamma proteobacteria

Georgina Hernández-Montes,José M Argüello,Brenda Valderrama

doi:10.1186/1471-2180-12-249

Georgina Hernández-Montes, José M Argüello + Show 1 more

Open Access

https://doi.org/10.1186/1471-2180-12-249

Copy DOI

Abstract

BackgroundDifferent systems contributing to copper homeostasis in bacteria have been described in recent years involving periplasmic and transport proteins that provide resistance via metal efflux to the extracellular media (CopA/Cue, Cus, Cut, and Pco). The participation of these proteins in the assembly of membrane, periplasmic and secreted cuproproteins has also been postulated. The integration and interrelation of these systems and their apparent redundancies are less clear since they have been studied in alternative systems. Based on the idea that cellular copper is not free but rather it is transferred via protein-protein interactions, we hypothesized that systems would coevolve and be constituted by set numbers of essential components.ResultsBy the use of a phylogenomic approach we identified the distribution of 14 proteins previously characterized as members of homeostasis systems in the genomes of 268 gamma proteobacteria. Only 3% of the genomes presented the complete systems and 5% of them, all intracellular parasites, lacked the 14 genes. Surprisingly, copper homeostatic pathways did not behave as evolutionary units with particular species assembling different combinations of basic functions. The most frequent functions, and probably because of its distribution the most vital, were copper extrusion from the cytoplasm to the periplasm performed by CopA and copper export from the cytoplasm to the extracellular space performed by CusC, which along with the remaining 12 proteins, assemble in nine different functional repertoires.ConclusionsThese observations suggest complex evolutionary dynamics and still unexplored interactions to achieve copper homeostasis, challenging some of the molecular transport mechanism proposed for these systems.

Highlights

Different systems contributing to copper homeostasis in bacteria have been described in recent years involving periplasmic and transport proteins that provide resistance via metal efflux to the extracellular media (CopA/Cue, Cus, Cut, and Pco)
Orthologs identification and profile construction We selected 14 different proteins known to be involved in copper homeostasis from three gamma proteobacterial isolates as seeds for BLAST searches of their orthologs: five proteins from Escherichia coli K12 MG1655 (CopA, composition: a substrate-binding inner membrane transporter (CusA), CusB, CusC and CusF), eight proteins from Escherichia coli O1:K1:H7 (APEC) (PcoA, PcoB, PcoC, PcoD, PcoE, CueO, YebZ and CutF), and one protein from Salmonella enterica subsp. enterica serovar Typhimurium LT2 (CueP)
Analysis of 268 gamma proteobacterial genomes (Additional file 1) by Bidirectional Best Hit (BBH) criterion allowed the identification of 1,417 orthologs to the seed proteins

Summary

Introduction

Different systems contributing to copper homeostasis in bacteria have been described in recent years involving periplasmic and transport proteins that provide resistance via metal efflux to the extracellular media (CopA/Cue, Cus, Cut, and Pco). The participation of these proteins in the assembly of membrane, periplasmic and secreted cuproproteins has been postulated. CusR and CusS activate the transcription of the cusCBAF operon that encodes for a complex that pumps Cu(I) to the extracellular space [11] This complex consists of the inner membrane pump CusA, the periplasmic protein CusB and the outer membrane protein CusC forming a channel through the periplasm. Since CutC is a cytoplasmic protein perhaps involved in intracellular trafficking of Cu(I), while CutF is an outer membrane protein [15], we only included CutF in our analysis Figure 1

Methods

Results

Discussion

Conclusion