The essential Staphylococcus aureus gene fmhB is involved in the first step of peptidoglycan pentaglycine interpeptide formation. Export

@article{citeulike:951583, abstract = {The factor catalyzing the first step in the synthesis of the characteristic pentaglycine interpeptide in Staphylococcus aureus peptidoglycan was found to be encoded by the essential gene fmhB. We have analyzed murein composition and structure synthesized when fmhB expression is reduced. The endogenous fmhB promoter was substituted with the xylose regulon from Staphylococcus xylosus, which allowed glucose-controlled repression of fmhB transcription. Repression of fmhB reduced growth and triggered a drastic accumulation of uncrosslinked, unmodified muropeptide monomer precursors at the expense of the oligomeric fraction, leading to a substantial decrease in overall peptidoglycan crosslinking. The composition of the predominant muropeptide was confirmed by MS to be N-acetylglucosamine-(beta-1,4)-N-acetylmuramic acid(-L-Ala-D-iGln-L-Lys-D-Ala-D-Ala), proving that FmhB is involved in the attachment of the first glycine to the pentaglycine interpeptide. This interpeptide plays an important role in crosslinking and stability of the S. aureus cell wall, acts as an anchor for cell wall-associated proteins, determinants of pathogenicity, and is essential for the expression of methicillin resistance. Any shortening of the pentaglycine side chain reduces or even abolishes methicillin resistance, as occurred with fmhB repression. Because of its key role FmhB is a potential target for novel antibacterial agents that could control the threat of emerging multiresistant S. aureus.}, address = {Institute of Medical Microbiology, University of Z\"{u}rich, Gloriastr. 32, Postfach, CH-8028 Z\"{u}rich, Switzerland.}, author = {Rohrer, S. and Ehlert, K. and Tschierske, M. and Labischinski, H. and Berger-B\"{a}chi, B.}, citeulike-article-id = {951583}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/10430946}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=10430946}, day = {3}, issn = {0027-8424}, journal = {Proc Natl Acad Sci U S A}, keywords = {fem, microbiology, staph}, month = {August}, number = {16}, pages = {9351--9356}, posted-at = {2006-11-19 10:45:21}, priority = {2}, title = {The essential Staphylococcus aureus gene fmhB is involved in the first step of peptidoglycan pentaglycine interpeptide formation.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/10430946}, volume = {96}, year = {1999} }

TY - JOUR ID - citeulike:951583 L3 - citeulike-article-id:951583 N2 - The factor catalyzing the first step in the synthesis of the characteristic pentaglycine interpeptide in Staphylococcus aureus peptidoglycan was found to be encoded by the essential gene fmhB. We have analyzed murein composition and structure synthesized when fmhB expression is reduced. The endogenous fmhB promoter was substituted with the xylose regulon from Staphylococcus xylosus, which allowed glucose-controlled repression of fmhB transcription. Repression of fmhB reduced growth and triggered a drastic accumulation of uncrosslinked, unmodified muropeptide monomer precursors at the expense of the oligomeric fraction, leading to a substantial decrease in overall peptidoglycan crosslinking. The composition of the predominant muropeptide was confirmed by MS to be N-acetylglucosamine-(beta-1,4)-N-acetylmuramic acid(-L-Ala-D-iGln-L-Lys-D-Ala-D-Ala), proving that FmhB is involved in the attachment of the first glycine to the pentaglycine interpeptide. This interpeptide plays an important role in crosslinking and stability of the S. aureus cell wall, acts as an anchor for cell wall-associated proteins, determinants of pathogenicity, and is essential for the expression of methicillin resistance. Any shortening of the pentaglycine side chain reduces or even abolishes methicillin resistance, as occurred with fmhB repression. Because of its key role FmhB is a potential target for novel antibacterial agents that could control the threat of emerging multiresistant S. aureus. IS - 16 JF - Proc Natl Acad Sci U S A SN - 0027-8424 AD - Institute of Medical Microbiology, University of Zürich, Gloriastr. 32, Postfach, CH-8028 Zürich, Switzerland. EP - 9356 TI - The essential Staphylococcus aureus gene fmhB is involved in the first step of peptidoglycan pentaglycine interpeptide formation. VL - 96 SP - 9351 KW - fem KW - microbiology KW - staph AU - Rohrer, S AU - Ehlert, K AU - Tschierske, M AU - Labischinski, H AU - Berger-Bächi, B PY - 1999/08/03/ UR - http://view.ncbi.nlm.nih.gov/pubmed/10430946 ER -