- Peptidoglycan Cross-Linking Preferences of Staphylococcus aureus Penicillin-Binding Proteins Have Implications for Treating MRSA Infections
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Methicillin-resistant Staphylococcus aureus (MRSA) infections are a global public health problem. MRSA strains have acquired a non-native penicillin-binding protein called PBP2a that cross-links peptidoglycan when the native S. aureus PBPs are inhibited by β-lactams. It has been proposed that the native S. aureus PBPs can use cell wall precursors having different glycine branch lengths (penta-, tri-, or monoglycine), while PBP2a can only cross-link peptidoglycan strands bearing a complete pentaglycine branch. This hypothesis has never been tested because the necessary substrates have not been available. Here, we compared the ability of PBP2a and two native S. aureus transpeptidases to cross-link peptidoglycan strands bearing different glycine branches. We show that purified PBP2a can cross-link glycan strands bearing penta- and triglycine, but not monoglycine, and experiments in cells provide support for these findings. Because PBP2a cannot cross-link peptidoglycan containing monoglycine, this study implicates the enzyme (FemA) that extends the monoglycine branch to triglycine on Lipid II as an ideal target for small molecules that restore sensitivity of MRSA to β-lactams.
- Srisuknimit, Veerasak,Qiao, Yuan,Schaefer, Kaitlin,Kahne, Daniel,Walker, Suzanne
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- Method for preparing ceftobiprole through one-pot reaction
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The invention discloses a method for preparing ceftobiprole through one-pot reaction. The method comprises the steps that a compound I and a compound II are prepared into a compound III through one to two hours of amidation under catalysis of organic alka
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Paragraph 0023; 0024; 0025
(2016/11/17)
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- METHOD FOR THE PRODUCTION OF CEFTOBIPROLE MEDOCARIL
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The present invention relates to a method for the production of organic compounds, in particular sodium (6R,7R)-7-[(Z)-2-(5-amino-[1,2,4]thiadiazol-3-yl)-2-hydroxyimino-acetylamino]-8-oxo-3-[(E)-(R)-1′-(5-methyl-2-oxo-[1,3]-dioxol-4-ylmethoxycarbonyl)-2-o
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- NEW CRYSTAL POLYMORPHS OF CEFTOBIPROLE
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A compound of formula (I) in a crystalline form, which has a X-ray diffraction pattern comprising, when measured using Cu- Kα1 radiation, a diffraction line, having a relative intensity (rl) of 100 percent at about 11.6, 12.9, 14.7, 22.0, 23.1 or 24.5, given in degrees 2 Theta [2θ]. Five corresponding polymorphic crystal forms (Polymorph A; B; C; D or E) have been characterized by means of their XRPD and have been isolated.
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Page/Page column 10
(2010/07/09)
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- Vinyl-pyrrolidinone cephalosporins
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The present invention relates to compounds having the formula STR1 wherein X, R1, R2, R3, R4, R5, R6, and R7 are as defined herein as well as readily hydrolyzable esters thereof, pharmaceutically acceptable salts of said compounds and hydrates of the compounds of formula I and of their esters and salts. These compounds have valuable pharmacological activity for the treatment and prophylaxis of infectious diseases, especially those caused by methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa.
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