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Copper-based compounds are widely used in agriculture as a chemical strategy to limit the spread of multiple plant diseases; however, the continuous use of this heavy metal has caused environmental damage as well as the development of copper-resistant strains. Thus, it is important to understand how the bacterial phytopathogens evolve to manage with this metal in the field. The MqsRA Toxin–Antitoxin system has been recently described for its function in biofilm formation and copper tolerance in  Xylella fastidiosa , a plant-pathogen bacterium responsible for economic damage in several crops worldwide. Here we identified differentially regulated genes by  X. fastidiosa  MqsRA by assessing changes in global gene expression with and without copper. Results show that  mqsR  overexpression led to changes in the pattern of cell aggregation, culminating in a global phenotypic heterogeneity, indicative of persister cell formation. This phenotype was also observed in wild-type cells but only in the presence of copper. This suggests that MqsR regulates genes that alter cell behavior in order to prime them to respond to copper stress, which is supported by RNA-Seq analysis. To increase cellular tolerance, proteolysis and efflux pumps and regulator related to multidrug resistance are induced in the presence of copper, in an MqsR-independent response. In this study we show a network of genes modulated by MqsR that is associated with induction of persistence in  X. fastidiosa . Persistence in plant-pathogenic bacteria is an important genetic tolerance mechanism still neglected for management of phytopathogens in agriculture, for which this work expands the current knowledge and opens new perspectives for studies aiming for a more efficient control in the field.

Overexpression of mqsR in Xylella fastidiosa Leads to a Priming Effect of Cells to Copper Stress Tolerance