It is now amply documented that cell surface macromolecular structures expressed by most microbial species mediate a variety of important physiological processes which govern how cells interact with their environment. An explicit description of these interactions will therefore be necessary for a more complete understanding of the molecular basis of pathogenicity. Among the many cell surface structures expressed by bacteria, polysaccharides are perhaps the most structurally diverse, and undoubtedly these molecules represent the outermost layer of the cell that is available for interaction with the environment. It is clear that further understanding of the molecular mechanisms of infectious disease processes will require detailed knowledge of the genes and gene products which participate in cell surface polysaccharide synthesis and assembly. To approach this problem in a manageable way, attention has been focused on the K1 antigen of Escherichia coli. The K1 antigen is composed of as many as 200 sialic acid residues which form unbranched homopolymeric chains attached to the cell envelope. How sialic acids are synthesized, assembled, and translocated from their site of synthesis at the inner membrane to their final location at the outer membrane therefore represents a problem of fundamental importance in molecular biology and in the specific area of membrane assembly. Immediate research aims require a description of the organization of the genes which participate in K1 antigen biosynthesis. By the use of recombinant DNA techniques, these genes have been isolated on a 30 to 35 kilobase fragment of DNA that defines a complex cluster of gene loci that are required for sialic acid synthesis and for polymer assembly. Application of classical genetic and recombinant DNA techniques to this gene cluster will reveal the details of its regulation and of its function in directing K1 antigen biosynthesis and expression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI023039-03
Application #
3134891
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1986-09-01
Project End
1989-12-31
Budget Start
1988-09-01
Budget End
1989-12-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Type
Schools of Veterinary Medicine
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
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Petter, J G; Vimr, E R (1993) Complete nucleotide sequence of the bacteriophage K1F tail gene encoding endo-N-acylneuraminidase (endo-N) and comparison to an endo-N homolog in bacteriophage PK1E. J Bacteriol 175:4354-63
Cieslewicz, M J; Steenbergen, S M; Vimr, E R (1993) Cloning, sequencing, expression, and complementation analysis of the Escherichia coli K1 kps region 1 gene, kpsE, and identification of an upstream open reading frame encoding a protein with homology to GutQ. J Bacteriol 175:8018-23

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