B-266. The dsdCXA Locus of Uropathogenic Escherichia coli Controls D-Serine Incorporation into Peptidoglycan

G. A. Baisa1, A. J. Schmidt1,2, R. A. Welch1;
1Univ. of Wisconsin, Madison, WI, 2Univ. of Iowa, Carver Coll. of Med., Iowa City, IA.

Most uropathogenic Escherichia coli (UPEC) strains possess the dsdCXA locus responsible for the degradation of D-serine to ammonia and pyruvate. D-serine is present throughout the human body and is especially found in high concentrations in urine. UPEC strain CFT073 readily grows in urine, but a CFT073 dsdA mutant lacking D-serine deaminase activity grows slowly and displays a large, swollen cellular morphology. We hypothesize that in the absence of a DsdA, D-serine accumulates intracellularly where it is misincorporated into peptidoglycan (PGN) leading to the altered growth and cellular phenotypes. Lysozyme-digested PGN samples isolated from CFT073 dsdA grown in the presence or absence of D-serine were analyzed by reversed-HPLC. Differences between the resulting chromatograms indicate that D-serine is either directly or indirectly altering PGN structure. 14C-D-serine PGN labeling experiments performed on CFT073 dsdA show that radioactive D-serine can be co-purified with the PGN which indicates that D-serine is directly incorporated into the PGN. CFT073 dsdA grown in the presence of D-serine displayed a synergistic inhibitory growth effect with an array of peptidoglycan synthesis inhibitors. This synergistic growth effect suggests the intracellular accumulation of D-serine is altering the cell envelope biogenesis. Our results support the hypothesis that a function of the dsdCXA locus in UPEC strains, when present in the urinary tract, is to control D-serine incorporation into the PGN layer.