# BIOSYNTHESIS OF BACTERIAL CELL WALL COMPONENTS

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 1990 · $191,494

## Abstract

The primary aim of our research plan is directed towards an
understanding of cell wall biosynthesis on the molecular level.
This research will provide insights into the processing of
peptidoglycan (PG), the mechanism of penicillin action, dynamics
of the assembly processes, levels of lipid bilayer organization, and
the biosynthesis and function of lipoteichoic acid.  Five specific
aims will be investigated.

(1)  It is our hypothesis that the cross-linking of PG in Gaffkya
homari occurs by a pathway that requires a penicillin-sensitive N-
acetylmuramyl-L-alanine amidase and a penicillin-insensitive
transpeptidase.  To support this hypothesis, it is our aim to isolate
the amidase from this organism and relate this enzyme to PBP-6,
the primary in vivo target of penicillin.
(2)  Penicillin also causes the enhanced secretion of water-soluble
PG, lipids, LTA and proteins.  It is our aim to establish the
mechanisms of the penicillin-induced release of these compounds.
(3)  The intramembranal mechanism of peptidoglycan formation is
not well understood.  It is our goal to use probe-labeled lipid
intermediates to study the dynamics of the assembly process, the
formation of lipid oligomers, and the membrane proteins in the
assembly complex.
(4)  Lipid bilayer organization plays an important role in the
assembly of PG.  It is our aim to develop an understanding of the
organization that is responsible for the association of membrane
and wall, and the organization of the PG assembly complex.
(5)  The D-alanyl esters of lipoteichoic acid appear to play a vital
function in cell division and separation.  It is our aim to establish
the molecular events required for the incorporation of D-alanine
and the transacylation of the D-alanyl ester residues.
Transacylation of these esters on the poly(glycerophosphate)
moiety may represent a unique way of transmitting a signal from
one location in the membrane to another.

The effects of antibiotics, e.g. penicillin, on well-characterized
assembly systems is instrumental to our definition of their
mechanisms of action.  As new target sites are described n these
systems, it is proposed that novel types of antibacterial agents
may be designed.  D-Alanyl-lipoteichoic acid has been implicated
in a variety of bacterial adhesion processes involved in the
infectious process.  This property may be modulated in part by the
D-alanyl ester residues.

## Key facts

- **NIH application ID:** 3124196
- **Project number:** 5R01AI004615-29
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **SAM.gov UEI:** EXZVPWZBLUE8
- **Principal Investigator:** FRANCIS C NEUHAUS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $191,494
- **Award type:** 5
- **Project period:** 1979-05-01 → 1992-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3124196

## Citation

> US National Institutes of Health, RePORTER application 3124196, BIOSYNTHESIS OF BACTERIAL CELL WALL COMPONENTS (5R01AI004615-29). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3124196. Licensed CC0.

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