RT Journal Article SR Electronic(1) A1 Patel, Sarju J. A1 Padilla-Benavides, Teresita A1 Collins, Jessica M. A1 Argüello, José M.YR 2014 T1 Functional diversity of five homologous Cu+-ATPases present in Sinorhizobium meliloti JF Microbiology, VO 160 IS 6 SP 1237 OP 1251 DO https://doi.org/10.1099/mic.0.079137-0 PB Microbiology Society, SN 1465-2080, AB 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., UL https://www.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.079137-0