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Review
. 2009 Oct;53(10):4051-63.
doi: 10.1128/AAC.00084-09. Epub 2009 May 26.

Molecular basis and phenotype of methicillin resistance in Staphylococcus aureus and insights into new beta-lactams that meet the challenge

Leticia I Llarrull  1 , Jed F Fisher, Shahriar Mobashery
Affiliations
Review

Molecular basis and phenotype of methicillin resistance in Staphylococcus aureus and insights into new beta-lactams that meet the challenge

Leticia I Llarrull et al. Antimicrob Agents Chemother. 2009 Oct.
No abstract available

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Figures

FIG. 1.
FIG. 1.
Schematic representation of cell wall synthesis in S. aureus. The transpeptidase and transglycosylase reactions assemble the peptidoglycan on the surface of the cytoplasmic membrane. The three-dimensional structure of the peptidogycan was recently solved by our laboratory (120a), and it is depicted as a Connolly surface with the sugar backbone (NAG-NAM polymer) in orange and the peptides in green. Two strands of peptidoglycan are shown with cross-linking through a peptide bridge shared between the two. NHAc, N-acetyl group.
FIG. 2.
FIG. 2.
(A) Stereo view of the active site of PBP 2a of S. aureus depicted as a Connolly solvent-accessible surface (green). The side chains of the active-site serine and lysine are shown as capped sticks and colored by atom types (carbon in gray, oxygen in red, and nitrogen in blue). The backbone of the loop that caps the active site is shown as an orange wire. (B) Stereo view of the active site from the same perspective shown in panel A, except the loop is now shown as a solvent-accessible surface for both the backbone and the side chain functionalities. The presence of the loop blocks the active-site access for molecules the size of typical β-lactam antibiotics.
FIG. 3.
FIG. 3.
Chemical structures of the β-lactam antibiotics that are in advanced stages of evaluation for the treatment of MRSA infections. The chemical groups that are cleaved upon activation of the ceftobiprole medocaril and ceftaroline fosamil prodrugs are highlighted in gray.
See this image and copyright information in PMC

References

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