Inhibitors of Peptidoglycan Synthesis.Penicillinsβ-lactams·Cephalosporins.Carbapenems and Monobactams·Glycopeptides,suchasvancomycinNbeta-lactam
Inhibitors of Peptidoglycan Synthesis • Penicillins • Cephalosporins • Carbapenems and Monobactams • Glycopeptides, such as vancomycin b-lactams
Mechanisms of Actionβ-lactamsNAG-NAMA-NAG-NAMANAG-NAMA-NNAG-NAMA白NAGNAMA-NAG-NAMA-NAG-vancomycin-NAG-NAMANAG-NAMA10Thehvdrolvsisofthe5thamino-acid providestheNAG-NAMA-NAenergynecessaryforthebindingNAG-N1) B-lactams inhibit the binding of the tetrapeptide chain to thechain of five glycineresidues.Vancomycin inhibits an earlier reaction.The weakening of the peptidoglycan leads to rupture of the cell wall.These drugs are therefore bactericidal
Mechanisms of Action 1） B-lactams inhibit the binding of the tetrapeptide chain to the chain of five glycine residues. Vancomycin inhibits an earlier reaction. The weakening of the peptidoglycan leads to rupture of the cell wall. These drugs are therefore bactericidal
2 β一lactam antibiotics can alsoincrease the activity of cell-wallautolytic enzyme
2）β－lactam antibiotics can also increase the activity of cell-wall autolytic enzyme
Bacteria resistanceBacteria produced β-lactamase2Trapping mechanism3.Bacteria altered PBPs with affinity for β-lactam antibiotics4. Lacking of porin protein , such as OmpFand OmpC5.Enhanced active eflux system6. Lacked autolysins
Bacteria resistance 1. Bacteria produced β－lactamase. 2. Trapping mechanism 3. Bacteria altered PBPs with affinity for β－ lactam antibiotics . 4. Lacking of porin protein , such as OmpF and OmpC 5. Enhanced active efflux system 6. Lacked autolysins
2. PENICILLINSPenicillin,discovered by A.Fleming in 1928, led to the developmentofalargeclass ofantimicrobial drugsstill widelyusedtodayPenicillin G and V are obtained by fermentation of a fungus calledpenicilliumUseofanamidaseenzyme-extracted fromEscherichiacoli-tomodify a side-chain led to the production of semi-syntheticpenicillins withextendedspectraBacilluscereuswithout, andwith,sub-lethalconcentrationofpenicillin
2. PENICILLINS Penicillin, discovered by A. Fleming in 1928, led to the development of a large class of antimicrobial drugs still widely used today Penicillin G and V are obtained by fermentation of a fungus called penicillium Use of an amidase enzyme–extracted from Escherichia coli- to modify a side-chain led to the production of semi-synthetic penicillins with extended spectra Bacillus cereus without, and with, sublethal concentratio n of penicillin