# LIGAND RECEPTOR INTERACTION IN BACTERIAL ADHERENCE

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 1988 · $101,370

## Abstract

The overall aim of this research project is to study the molecular
mechanisms of the adherence of bacteria to mammalian cells.  For this
purpose the lipoteichoic acid-mediated attachment of group A streptococci
and the type 1 fimbriae-mediated attachment of Escherichia coli will be
studied in detail as paradigms of the process of adhesion and
colonization.  Specific efforts will be directed toward:  (1) defining the
structural domain(s) of the fibronectin molecule on oropharyngeal
epithelial cells that recognize group A streptococci and its lipoteichoic
acid, (2) defining the orientation and the anchorage of the lipoteichoic
acid-protein complex on the surface of intact streptococci, (3) defining
primary tertiary and quaternary structural determinants of type I fimbriae
of E. coli that mediate the binding to mannose-containing receptors on
eukaryotic cells; monoclonal antibodies will be employed to define the
structural elements necessary for binding, and (4) determining the
protective activity of monoclonal antibodies directed against primary,
tertiary and quaternary structural epitopes of type I fimbriae in a mouse
model of E. coli-induced pyelonephritis.  Human plasma fibronectin will be
purified by affiniity chromatography over gelatin and arginine Sepharose
columns.  The molecule will be cleaved with various proteolytic enzymes and
the fragments examined for binding to streptococci and LTA employing radio
immunochemical techniques in combination with electroimmunoblotting.  The
formation of complexes between M protein and LTA will be studied by
immunoelectrophoresis, radiolabeling techniques and by preparing
lipoteichoic acid substituted to varying degrees with alanine residues.
Native and synthetic subpeptides of M protein will be used to determine the
minimum structure required for complex formation.  Type I fimbriase will be
purified from E coli and used to prepare sets of monoclonal antibodies
directed against various structural epitopes.  The reactivities of the
antibodies with dissociated and reassembled fimbriae will be studied in
vitro and in vivo.  Mice will be injected intraperitoneally with monoclonal
antibodies and challenged intravesically with type I fimriated E. coli 24
hrs later.  Colonization by the organisms will be evaluated by culturing
samples of the kidney and bladder 5 days after challenge.  The proposed
studies should provide information needed to develop new approaches to the
prevention of serious infectious diseases arising from bacterial
colonization of susceptible mucosal surfaces.

## Key facts

- **NIH application ID:** 3125473
- **Project number:** 5R01AI013550-13
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **SAM.gov UEI:** X1M1PN3KG3E7
- **Principal Investigator:** EDWIN H. BEACHEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $101,370
- **Award type:** 5
- **Project period:** 1976-08-01 → 1989-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125473

## Citation

> US National Institutes of Health, RePORTER application 3125473, LIGAND RECEPTOR INTERACTION IN BACTERIAL ADHERENCE (5R01AI013550-13). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125473. Licensed CC0.

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