# ROLE OF PEPTIDOGLYCAN IN HEALTH AND DISEASE

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 1989 · $173,434

## Abstract

The underlying hypothesis for this project is that soluble
peptidoglycan (PG) fragments liberated from bacteria modulate the
host response during the course of natural infections.  The test
of this hypothesis exploits two distinct PG-mediated biological
reactions.  The first system is based on our previous suggestion
that PG derived for Neisseria gonorrhoeae contributes to the acute
inflammatory reactions, e.g., urethritis and arthritis,
characteristic of local and disseminated gonococcal infections,
respectively.  The second is based on the intriguing revelation
that certain PG fragments accumulate in the brains of sleep-
deprived animals and function as natural enhancers of slow-wave
sleep.  Our goal is to define the mechanisms behind these pro-
inflammatory and sleep-promoting properties of PG.  Toward this
end, we will exploit a unique series of physiologically realistic
PG fragments, e.g., N-acetylglucosaminlyl-1,6-anhydro-N-
acetylmuramyl-alanyl-glutamyl-diaminopimelyl-alanine, which are
purified to homogeneity by reversed-phase HPLC, unambiguously
defined by fast-atom bombardment-mass spectrometry and, for some
purposes, labeled to very high specific activity with tritium.  In
conjunction with assay systems for quantitating the release of
soluble PG by cultured bacteria and for examining the interactions
of PG fragments with the intact host and with cultured host cells,
the PG library will be employed to test the following integrated
series of hypotheses, (1) that endogenous gastrointestinal flora
turn over and release PG fragments (ii) that PG fragments in the
gastrointestinal tract cross the intact mucosal epithelium and
enter the vascular system, (iii) that some PG fragments ultimately
localize in potential target tissues, including the joints and the
central nervous system, where they might trigger a cascade of
events leading to arthritis and enhanced sleep, respectively, (iv)
that PG-mediated arthropathic and somnogenic activities are
associated with modulation of the release of common mediators, such
as interleukin-1, form specific cultured target cells, e.g.,
synovial fibroblasts and astroglial cells, and (v) that the ability
of PG fragments to cause arthritis, enhance sleep and modulate
release of mediators is associated with the specific binding of PG
determinants to receptors on susceptible target cells.  We feel
the defining the cellular and molecular events involved in
gonococcal PG-arthritis and enhancement of slow-wave sleep may
reveal common mechanisms that operate whenever a biologically
relevant burden of these versatile effector molecules gain access
to specific host tissues.

## Key facts

- **NIH application ID:** 3125891
- **Project number:** 2R01AI014826-11A1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **SAM.gov UEI:** SHHBRBAPSM35
- **Principal Investigator:** RAOUL S ROSENTHAL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $173,434
- **Award type:** 2
- **Project period:** 1978-05-01 → 1994-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125891

## Citation

> US National Institutes of Health, RePORTER application 3125891, ROLE OF PEPTIDOGLYCAN IN HEALTH AND DISEASE (2R01AI014826-11A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125891. Licensed CC0.

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