Regulation of gene transcription by GadE and other acid tolerance gene products.

Uropathogenic (UPEC) cause millions of urinary tract infections each year in the United States. Type 1 pili are important for adherence of UPEC to uroepithelial cells in the human and murine urinary tracts where osmolality and pH vary. Previous work has shown that an acidic pH adversely affects the expression of type 1 pili. To determine if acid tolerance gene products may be regulating gene expression, a bank of K-12 strain acid tolerance gene mutants were screened using , and fusions on single copy number plasmids. We have determined that a mutation in increased transcription of all three genes, suggesting that GadE may be acting as a repressor in a low pH environment. Complementation of the mutation restored gene transcription to wild-type levels. Moreover, mutations in and also affected transcription of the three genes. To verify the role GadE plays in type 1 pilus expression, the NU149 UPEC strain was tested. The mutant had higher gene transcript levels, a higher frequency of Phase-OFF positioning of , and hemagglutination titres that were lower in strain NU149 cultured in low pH medium as compared to the wild-type bacteria. The data demonstrate that UPEC genes are regulated directly or indirectly by the GadE protein and this could have some future bearing on the ability to prevent urinary tract infections by acidifying the urine and shutting off gene expression.