Rita Ciorbaru

Minimal structural requirements for adjuvant activity of bacterial peptidoglycan derivatives

Abstract We have recently shown that the monomeric subunit of mesodiaminopimelic acid containing bacterial peptidoglycans, i. e. the disaccharide tetrapeptide N-acetyl glucosaminyl-N-acetyl muramyl-L-alanyl-D-isoglutaminyl-meso-diaminopimelyl-D-alanine can replace whole killed mycobacteria in Freunds adjuvant. We now report further structural simplifications of the active molecule; natural N-acetyl-muramyl-tripeptides have been found active; the smallest adjuvant molecule found is a synthetic N-acetyl muramyl-dipeptide prepared by Sinay et al. (1).

Adjuvant activity of monomeric bacterial cell wall peptidoglycans.

Abstract We have previously shown that lysozyme solubilized cell walls of Mycobacteria or Nocardiae can replace whole mycobacterial cells or Wax D in Freunds complete adjuvant and it was found quite recently that hydrosoluble peptidoglycans, free of neutral sugars, are also adjuvant active. We show now that the simplest fragment tested — the disaccharide tetrapeptide (I) — increases circulating antibodies to ovalbumin and induces a delayed hypersensitivity toward this antigen. Similar compounds obtained from the basal layer of the cell wall of E. coli are also active. Thus the immunoadjuvant activity of soluble cell wall peptidoglycans is a property of the monomeric unit and is not restricted to acid fast bacteria.

Chemical Structure of Mycobacterial Cell Walls

Many of the immunostimulant effects of living or killed cells of mycobacteria can be obtained with isolated cell walls: protection against tuberculosis [25, 26], stimulation of nonspecific resistance against infections [14, 22], adjuvant activity [4, 11], stimulation of resistance to tumors [12] and tumor suppression [34].