Autotransporters are the most abundant family of secreted proteins in gram-negative bacteria. Many of those that have been characterized are virulence proteins. We have previously shown that autotransporter proteins are secreted at the bacterial pole and that these proteins are targeted to the pole in the bacterial cytoplasm, prior t secretion across the cytoplasmic membrane. Our preliminary data indicate that the cell division protein FtsQ is involved in establishing polar positional information recognized by autotransporters and that the periplasmic domain of FtsQ is sufficient for the generation of this information. We propose exploratory investigations into the role of cell envelope remodeling in the establishment of polar positional information that is recognized in the cytoplasm by autotransporter proteins.
Our specific aims are: 1. Characterize mutants of FtsQ defective in establishing polarity of the Shigella spp. autotransporter IcsA. 2. Identify using an unbiased approach, and characterize, proteins in the pathway downstream of FtsQ in autotransporter polarity. 3. Identify using a candidate approach, and characterize, proteins that interact with FtsQ in the autotransporter polarity pathway. The exploratory investigations we propose in this application will generate insights into the mechanisms involved in the establishment of polarity and into the dynamic development and remodeling of the cell envelope in prokaryotes.

Public Health Relevance

Bacteria interact with human hosts largely through proteins that are present on the bacterial surface. Among disease-causing bacteria, members of a large family of proteins that contribute to disease processes are specifically positioned on the end of the bacteria, where they engage their hosts. Our investigations into the mechanisms involved in proper positioning of these proteins will provide insights into the linkage between bacterial cell organization and disease.

National Institute of Health (NIH)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1)
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Mills, Melody
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Massachusetts General Hospital
United States
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