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

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 muropep

Synthesis of Mosaic Peptidoglycan Cross-bridges by Hybrid Peptidoglycan Assembly Pathways in Gram-positive Bacteria

“…In S. aureus, transferases essential for incorporation of residues at specific positions of the pentaglycine side chain (Fig. 1) have been identified based on gene inactivation (femA and femB) and conditional gene expression (fmhB) (11,12). Individual inactivation of two additional femrelated genes had little impact on viability and amino acid composition of the peptidoglycan (29).…”

“…1) is an essential enzyme. This indicates that unsubstituted pentapeptide stems cannot be cross-linked (11). In addition, femA and femB mutants of methicillin-resistant S. aureus are susceptible to methicillin.…”

Aminoacyl-tRNAs, the bacterial cell envelope, and antibiotics

“…Inhibition of pentaglycine bridge formation reduces methicillin resistance, leading to ␤-lactam hypersusceptibility (21). The enzyme catalyzing the first step in the synthesis of the pentaglycine bridge in S. aureus peptidoglycan was shown to be encoded by fmhB (also called femX), an essential gene (20). Similar work carried out in Streptococcus pneumoniae (7) has also shown that high-level penicillin resistance is associated with modifications in the structure of the peptidoglycan (22).…”

“…In S. aureus, including the methicillinresistant strains, a pentaglycine bridge cross-links the peptidoglycan stem peptides (18,20). Inhibition of pentaglycine bridge formation reduces methicillin resistance, leading to ␤-lactam hypersusceptibility (21).…”

Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus in Finland

“…Insertional inactivation studies have identified several normal staphylococcal genes necessary for methicillin resistance. Mutations in these fem (factors essential for methicillin resistance) or aux (auxilliary) factors inhibit the peptodoglycan precursor for- (230,256). Amidation of glutamate in the stem peptide is inhibited in femC (or glnR) mutants (97,257), glucosamine-1-phosphate formation is inhibited in femD (or femR or glmM) mutants (124), and precursor formation is blocked at the lysine addition step in femF mutants (202).…”