@article{mbs:/content/journal/micro/10.1099/mic.0.079137-0, author = "Patel, Sarju J. and Padilla-Benavides, Teresita and Collins, Jessica M. and Argüello, José M.", title = "Functional diversity of five homologous Cu+-ATPases present in Sinorhizobium meliloti", journal= "Microbiology", year = "2014", volume = "160", number = "6", pages = "1237-1251", doi = "https://doi.org/10.1099/mic.0.079137-0", url = "https://www.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.079137-0", publisher = "Microbiology Society", issn = "1465-2080", type = "Journal Article", abstract = "Copper is an important element in host–microbe interactions, acting both as a catalyst in enzymes and as a potential toxin. Cu+-ATPases drive cytoplasmic Cu+ efflux and protect bacteria against metal overload. Many pathogenic and symbiotic bacteria contain multiple Cu+-ATPase genes within particular genetic environments, suggesting alternative roles for each resulting protein. This hypothesis was tested by characterizing five homologous Cu+-ATPases present in the symbiotic organism Sinorhizobium meliloti. Mutation of each gene led to different phenotypes and abnormal nodule development in the alfalfa host. Distinct responses were detected in free-living S. meliloti mutant strains exposed to metal and redox stresses. Differential gene expression was detected under Cu+, oxygen or nitrosative stress. These observations suggest that CopA1a maintains the cytoplasmic Cu+ quota and its expression is controlled by Cu+ levels. CopA1b is also regulated by Cu+ concentrations and is required during symbiosis for bacteroid maturation. CopA2-like proteins, FixI1 and FixI2, are necessary for the assembly of two different cytochrome c oxidases at different stages of bacterial life. CopA3 is a phylogenetically distinct Cu+-ATPase that does not contribute to Cu+ tolerance. It is regulated by redox stress and required during symbiosis. We postulated a model where non-redundant homologous Cu+-ATPases, operating under distinct regulation, transport Cu+ to different target proteins.", }