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Bacterial gene regulation and chronic infection
Research description:
In Salmonella enterica serovar Typhimurium (S. Typhimurium), the expression of virulence factors is highly regulated. The bacteria appear capable of sensing alterations in environmental cues, and regulate the expression of virulence factors accordingly. Mutations that affect gene regulatory patterns actually may lead to avirulence or alter the normal acute infection to persistent carriage.
This project studies gene regulatory circuits relevant for the intracellular infection of salmonella. We have applied micro-array technology to define the change of the bacterial transcriptome as the bacteria enter and starts replicating in macrophages. Such analyses show extraordinary large differences in the transcriptomes of extra- and intracellular bacteria. We have isolated mutants affected in the regulation of the intracellular transcriptome and demonstrated that selected such mutants actually possess an altered infection pathogenesis with the ability to establish a chronic carrier state in immunocompetent mice. In this context we are also analyzing the effect of newly defined gene regulators. We are particularly interested in the role of exoribonucleases as gene regulatory factors. In addition, we have identified in S. Typhimurium gene functions that are not needed for the establishment or execution of an infection, but which are essential for the establishment of the chronic carrier state.
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