There are three main mechanisms through which bacteria can develop resistance against beta-lactams, namely,developing PBPs with lower affinity for beta-lactam, reducing access to PBPs, or developing enzymes which act against the antibiotics, known as beta-lactamases (Rice 2012).
The first method,that of producing new PBPs is most common in gram-positive bacteria, such as Staphylococcus aureus, which produces PBP2a,or Enterococcus faecium, which produces PBP5 (Rice 2012).
Gram-negative bacteria however favour the production of beta-lactamases (Rice 2012). These enzymes9e similar in structure to PBPs, and so are able to catalyse the hydrolisation of the beta-lactam ring, rendering the antibiotic ineffective (Andersson, Terwisscha, & Valegard …show more content…
The main glycopeptide in use is vancomycin (Calderon & Sabundayo 2007).
Function
Similar to beta-lactams, glycopeptides work by inhibiting synthesis of the cell wall (Calderon & Sabundayo 2007). However, instead of inhibiting the PBP enzymes responsible for catalysing peptidoglycan cross-linkage, glycopeptides such as vancomycin target the peptidoglycan precursor molecules (Geisel, Schmitz, Fluit, & Labischinski 2001). The terminal D-alanine on these precursors binds to the vancomycin, and so loses its affinity for the PBPs. As such,it cannot undergo transpeptidation,a vital step in peptidoglycan cross-linkage in cell wall synthesis (Rice 2012).
Mechanisms of Resistance
Because vancomycin function is dependent on the presence of a terminal D-alanine residue,the mutation allowing Enterococcus faecium to replace it with D-lactate reduces the glycopeptide's affinity for the precursor molecule to ineffective levels (Geisel 2001). This mutation occurs in the mobile part of the bacteria's DNA, allowing for transfer between species of a high level of resistance (Geisel
The first method,that of producing new PBPs is most common in gram-positive bacteria, such as Staphylococcus aureus, which produces PBP2a,or Enterococcus faecium, which produces PBP5 (Rice 2012).
Gram-negative bacteria however favour the production of beta-lactamases (Rice 2012). These enzymes9e similar in structure to PBPs, and so are able to catalyse the hydrolisation of the beta-lactam ring, rendering the antibiotic ineffective (Andersson, Terwisscha, & Valegard …show more content…
The main glycopeptide in use is vancomycin (Calderon & Sabundayo 2007).
Function
Similar to beta-lactams, glycopeptides work by inhibiting synthesis of the cell wall (Calderon & Sabundayo 2007). However, instead of inhibiting the PBP enzymes responsible for catalysing peptidoglycan cross-linkage, glycopeptides such as vancomycin target the peptidoglycan precursor molecules (Geisel, Schmitz, Fluit, & Labischinski 2001). The terminal D-alanine on these precursors binds to the vancomycin, and so loses its affinity for the PBPs. As such,it cannot undergo transpeptidation,a vital step in peptidoglycan cross-linkage in cell wall synthesis (Rice 2012).
Mechanisms of Resistance
Because vancomycin function is dependent on the presence of a terminal D-alanine residue,the mutation allowing Enterococcus faecium to replace it with D-lactate reduces the glycopeptide's affinity for the precursor molecule to ineffective levels (Geisel 2001). This mutation occurs in the mobile part of the bacteria's DNA, allowing for transfer between species of a high level of resistance (Geisel