Human Drug For Treating Bacterial Infections

2094 WordsNov 27, 20149 Pages
β-lactam antibiotics have continued to be the most popular drug for treating bacterial infections since its discovery in 1928 by Fleming and its introduction as an antibacterial agent in the early 1950.1 Most commonly used β-lactam drugs today stems from the original discovery and development of natural products from microorganisms like penicillin, cephalosporin and other β-lactam based antibiotics (Figure 1). 1,2 However, soon after its commercialization and widespread usage, β-lactamase secreting penicillin resistant strains of Staphylococcus aureus were isolated.3 The introduction of methicillin (a β-lactamase-insensitive semi-synthetic penicillin), to curb the resistance problem resulted in the evolution of another resistant strain known as methicillin-resistant Staphylococcus aureus (MRSA).4 Figure 1: Some β-lactam antibiotics Resistance to β-lactams is easy for bacteria as all β-lactams shared the same mode of action, which is the inhibition of bacterial cell wall synthesis by forming stable covalent adducts with the active site serine residues of penicillin binding proteins (PBPs). The PBPS are often divided into two partitions; the high molecular weight PBPs (HMW-PBPs) and the low-molecular weight PBPs (LMW-PBPs). The HMW-PBPs are further divided in two classes, A and B, while the LMW-PBPs are divided in four subclasses based on their tertiary structures. Figure 2 shows the reactions between natural substrates, β lactams and transition state analogs with the
Open Document