Our strategy based in the identification of orthologs of 14 seed

Our strategy based in the identification of orthologs of 14 seed proteins involved in copper homeostasis in 268 gamma proteobacterial genomes from 79 genera. This data was further transformed into a presence/absence matrix and optimized, preserving the phylogenetic relationships

of the organisms. It was striking to observe that only 3% of the organisms present the full copper homeostasis proteins Selumetinib clinical trial repertoire that was previously described in E.coli[7]. Interestingly, isolates presenting a large number of protein involved in copper homeostasis are pathogenic: Klebsiella pneumoniae NTUH-K2044, Klebsiella pneumoniae subsp. pneumoniae MGH 78578, Enterobacter cloacae subsp. cloacae ATCC 13047 and Escherichia coli 55989 are human pathogens; Escherichia

coli APEC O1 is a chicken pathogen and Escherichia coli ATCC 8739, Cronobacter sakazakii ATCC BAA-894 and Cronobacter turicensis TAX413502 may be opportunistic GDC-0449 molecular weight organisms. Although these organisms are well characterized, no relevant information about their biology or their lifestyles explained why these organisms present the largest repertoire of copper tolerance proteins. On the other hand, 5% of the organisms (all of them intracellular parasites) apparently lack copper homeostasis proteins. In the remaining organisms, the ensemble Rebamipide consolidated in four clusters: PcoC-CueO-YebZ-CutF-CusF, PcoE-PcoD, PcoA-PcoB and CusC-CusA-CusB-CopA, that pointed the most frequent strategies to address the necessary copper homeostasis. In this context, it is remarkable that the observed clusters were not fully consistent with evidence obtained from transcriptional co-regulation which has been fundamental for systems designation. In general, clusters distributed with phylogenetic consistency at the family level, suggesting inheritance as the main mechanism for gene transfer.

However, in some organisms harboring the full copper homeostasis repertoire, genes were organized as islands in plasmids and flanked by mobile elements, enabling them with the potential to be horizontally transferred (Additional file 2). Double optimization of the presence/absence profile exposed a tight organization of the seed proteins into nine different repertoires revealing the diversity of copper homeostasis in gamma proteobacteria. Redundancy is a common approach to improve the reliability and availability of a system. Adding redundancy increases the cost and complexity of a system design but if the cost of failure is high enough, redundancy may be an attractive option.

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