Hha Is a Negative Modulator of Transcription of hilA, the Salmonella enterica Serovar Typhimurium Invasion Gene Transcriptional Activator

AUTOR(ES)

Fahlen, Thomas F.

FONTE

American Society for Microbiology

RESUMO

An early step in the establishment of Salmonella enterica serovar Typhimurium murine infection is the penetration of the intestinal mucosa of the small intestine. The majority of the genes responsible for the Salmonella invasive phenotype are encoded on Salmonella pathogenicity island 1, and their transcription is controlled by the hilA transcriptional activator. The expression of hilA is regulated by environmental signals including oxygen, osmolarity, pH, and growth phase such that the presence of any one suboptimal condition results in repression of hilA expression and the invasive phenotype. We have conducted a search for negative regulators of hilA by introduction of a Salmonella enterica serovar Typhimurium chromosomal DNA gene bank into a Salmonella enterica serovar Typhimurium hilA::Tn5lacZY reporter strain. This screen has identified the hha gene as a regulator that exerts a negative influence on hilA expression. Plasmid-encoded hha significantly reduces hilA::Tn5lacZY chromosomal expression, as well as expression of the invasion genes invF, prgH, and sipC. An hha null mutation results in substantial derepression of both chromosomally encoded and plasmid-encoded hilA::Tn5lacZY expression. Introduction of plasmid-encoded hha into strain SL1344 results in attenuation of invasion using in vitro and in vivo assays. Importantly, purified Hha protein was found to bind to a hilA DNA promoter fragment, suggesting that the regulatory activity of the Hha protein occurs at the hilA promoter. These data add detail to the developing model of the regulation of Salmonella invasion genes.

Documentos Relacionados

• Transcription of the Salmonella Invasion Gene Activator, hilA, Requires HilD Activation in the Absence of Negative Regulators
• Multiple Factors Independently Regulate hilA and Invasion Gene Expression in Salmonella enterica Serovar Typhimurium
• HilE Interacts with HilD and Negatively Regulates hilA Transcription and Expression of the Salmonella enterica Serovar Typhimurium Invasive Phenotype
• Roles of hilC and hilD in Regulation of hilA Expression in Salmonella enterica Serovar Typhimurium
• The Small Nucleoid-Binding Proteins H-NS, HU, and Fis Affect hilA Expression in Salmonella enterica Serovar Typhimurium