THE ROLE OF FUR IN THE ACID TOLERANCE RESPONSE OF SALMONELLA-TYPHIMURIUM IS PHYSIOLOGICALLY AND GENETICALLY SEPARABLE FROM ITS ROLE IN IRONACQUISITION

The response of Salmonella typhimurium to low pH includes a low-pH pro tection system called the acid tolerance response (ATR). The iron-regu latory protein Fur has been implicated in the ATR since fur mutants ar e acid sensitive and cause altered expression of several acid shock pr oteins (J. W. Foster, J. Bacteriol. 173:6896-6902, 1991). We have dete rmined that the acid-sensitive phenotype of fur mutations is indeed du e to a defect in Fur that can be complemented by a fur(+)-containing p lasmid. However, changes in cellular iron status alone did not trigger the ATR. Cells clearly required exposure to low pH in order to induce acid tolerance. The role of Fur in acid tolerance was found to extend beyond regulating iron acquisition. A mutation in fur converting hist idine 90 to an arginine (H90R) eliminated Fur-mediated iron regulation of enterochelin production and deregulated an iroA-lacZ fusion but ha d no effect on acid tolerance. The H90R iron-blind Fur protein also me diated acid shock induction of several Fur-dependent acid shock protei ns and acid control of the hyd locus. In addition, a Fur superrepresso r that constitutively repressed iron-regulated genes mediated normal F ur-dependent acid tolerance and pH-controlled gene expression. The res ults indicate the acid-sensing and iron-sensing mechanisms of Fur are separable by mutation and reinforce the concept of Fur as a major glob al regulator in the cell.