Homeostatic control of iron- and manganese-dependent bacterial physiology and the impact of these metals on multicellular interactions of <i>Agrobacterium tumefaciens</i>
Transition metals from the first row of the periodic table, including iron and manganese are critical micronutrients for nearly all forms of life. However, they are also generally limiting in the environment and toxic at high concentrations. I have used genetic and physiological approaches to define the regulatory systems that the plant pathogenic bacterium Agrobacterium tumefaciens uses to sense varying levels of environmental iron and manganese and control the expression of metal uptake and utilization systems. The regulation of these systems allows A. tumefaciens to maintain sufficient cellular levels of iron and manganese for growth while preventing the accumulation of toxic levels of either metal. Using microarray analysis, I showed that varied iron availability induces major alterations in the gene expression profile. This study of the transition metal physiology of A. tumefaciens included an examination of the role iron and manganese play in mediating biofilm formation. Limiting amounts of either iron or manganese were found to decrease the biofilm formation of A. tumefaciens. Interestingly, disruption of the iron-responsive regulatory circuitry did not alter or abolish the impact of iron on biofilms, whereas de-repression of the manganese uptake systems resulted in a slight increase in biofilm formation. Finally, iron mediates the interactions between A. tumefaciens and the environmental and opportunistically pathogenic bacterium Pseudomonas aeruginosa. Iron limitation stimulates P. aeruginosa to produce a secreted, soluble compound that inhibits the biofilm formation by A. tumefaciens and fosters biofilm dispersal.