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

Citation
S. Rohrer et al., The essential Staphylococcus aureus gene fmhB is involved in the first step of peptidoglycan pentaglycine interpeptide formation, P NAS US, 96(16), 1999, pp. 9351-9356
Citations number
33
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN journal
0027-8424 → ACNP
Volume
96
Issue
16
Year of publication
1999
Pages
9351 - 9356
Database
ISI
SICI code
0027-8424(19990803)96:16<9351:TESAGF>2.0.ZU;2-O
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 composit ion and structure synthesized when fmhB expression is reduced, The endogeno us fmhB promoter was substituted with the xylose regulon from Staphylococcu s xylosus, which allowed glucose-controlled repression of fmhB transcriptio n. Repression of fmhB reduced growth and triggered a drastic accumulation o f uncrosslinked, unmodified muropeptide monomer precursors at the expense o f the oligomeric fraction, leading to a substantial decrease in overall pep tidoglycan crosslinking. The composition of the predominant muropeptide was confirmed by RIS to be N-acetyrglucosamine-(beta-1,4)-N-acetylmuramic acid (-L-Ala-D-iGln-L-Lys-D-Ala-D-Ala), proving that FmhB is involved in the att achment of the first glycine to the pentaglycine interpeptide. This interpe ptide plays an important role in crosslinking and stability of the S. aureu s cell wall, acts as an anchor for cell nail-associated proteins, determina nts of pathogenicity, and is essential for the expression of methicillin re sistance. Any shortening of the pentaglycine side chain reduces or even abo lishes methicillin resistance, as occurred with fmhB repression. Because of its keg role FmhB is a potential target for novel antibacterial agents tha t could control the threat of emerging multiresistant S. aureus.