Small fractions of many penicillin-sensitive bacterial species remain viable despite prolonged inhibition by penicillin or other Beta lactam antibiotics. Such persisters are neither more resistant nor more likely to survive anothe exposure to penicillin than normal cells. A newly recognized gene at 33.9 feet of Escherichia coli chromosome which effects the frequency of persistence has been identified by analysis of high persistence (hip) mutants and the parent (hip+). The characteristic frequencies of persistence, 10tothe-2 for hip and 10tothe-5 for hip+ are observed with any inhibitor of murein synthesis, not just that by Beta lactams. This project seeks to discover the mechanism of persistence by examining the normal function of hip+. The specific objectives are to clone the hip+ or hip genes in order to: 1) determine dominance and the effect of copy number on phenotypes; and 2) identify the hip+ or hip protein, determine its cellular location, and study its regulation. Persistence is of both practical and theoretical importance. Its potential involvement in persistent infection has long been suspected; indeed, intractable infection led to its discovery shortly after the introduction of penicillin. Persistence may be a product of the interaction of the bacterial division cycle and regulatory coupling of murein synthesis and the synthesis of other macromolecules. Finally the newly recognized gene, hip+, and its location in a region with few known functions are inherently interesting and present an opportunity to explore the mechanism of persistance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI020276-03
Application #
3129842
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1983-07-01
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Type
Schools of Medicine
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697