240 Bacterial Cell Wall Peptidoglycan and Teichoic Acid

Thursday, November 5, 2009: 10:20 AM
Hereford (Camino Real Hotel)
Charles V. Rice , Department of Chemistry and Biochemistry, The University of Oklahoma, Norman, OK
The conformation of D-alanine groups of bacterial teichoic acid is a central, yet untested, paradigm of microbiology.  The D-Ala binds through the carboxyl, hence the amine exists as a free NH3+ group with the ability to form a contact-ion-pair with the nearby anionic phosphate group.  This conformation hinders metal chelation by the phosphate because the zwitterion pair is charge neutral.  To the contrary, the repulsion of cationic antimicrobial peptides (CAMPs) is attributed to the presence of the D-Ala cation, thus the ion-pair does not form in this model.  Solid-state NMR spectroscopy has been used to measure the distance between amine and phosphate groups within cell wall fragments of Bacillus subtilis.  The bacteria were grown on media containing 15N D-alanine and b-chloroalanine racemase inhibitor.  The rotational-echo double-resonance (REDOR) pulse sequence was used to measure the internuclear dipolar coupling and the results demonstrate 1) the amine-to-phosphate distance is 4.5 Å and 2) increases to 5.4 Å when Mg2+ ions are present.  As a result, the zwitterion exists as a solvent-separated configuration providing teichoic acid with a positive charge to repel CAMPs.  Additionally, the amine of D-Ala does not prevent magnesium chelation in contradiction to the prevailing view of teichoic acids in metal binding.  Thus, the NMR-based description of teichoic acid structure resolves the contradictory models, advances the basic understanding of cell wall biochemistry, and may provide a direction to create new antibiotic therapies.