Beta-lactam antibiotics
Beta-lactam antibiotics are a class of antibiotics that share a common structural feature called the beta-lactam ring. This ring is crucial for their antibacterial activity. It works by inhibiting the synthesis of bacterial cell walls, which are essential for their structural integrity and survival.
Here's a breakdown of how beta-lactam antibiotics work:
1. Cell Wall Synthesis:, Bacteria have a cell wall that provides structural support and protection. This cell wall is primarily composed of peptidoglycan, a complex molecule. The formation of peptidoglycan involves the cross-linking of individual sugar molecules by enzymes known as transpeptidases.
2. Beta-lactam Ring Interaction:, Beta-lactam antibiotics, which include penicillins, cephalosporins, carbapenems, and monobactams, have a four-membered beta- lactam ring in their chemical structure. This ring is structurally like the D-Ala-D-Ala portion of peptidoglycan, which is the target of transpeptidases.
3. Inhibition of Transpeptidases: ,When a beta-lactam antibiotic is present, it binds to the transpeptidases and inactivates them. This prevents the formation of the cross- links in the peptidoglycan structure, weakening the bacterial cell wall.
4. Osmotic Lysis:, Without proper cross-linking, the bacterial cell wall becomes weak. When the bacterium tries to grow and divide, the cell wall cannot withstand the internal pressure, leading to osmotic lysis (bursting) of the cell.
Literature:
Basic and Clinical Pharmacology by Bertram G. Katzung, Susan B. Masters, and Anthony J. Trevor.
Review of Medical Microbiology and Immunology by Warren Levinson.
Goodman & Gilman's The Pharmacological Basis of Therapeutics edited by Laurence Brunton, Bruce Chabner, and Björn Knollmann.
National Center for Biotechnology Information (NCBI) - Beta-lactam antibiotics
Beta-lactamases are enzymes produced by bacteria that confer resistance to beta- lactam antibiotics, such as penicillins, cephalosporins, and carbapenems. They do this by breaking the beta-lactam ring, which is a crucial structural component of these antibiotics. Here is a brief overview along with some relevant literature on beta- lactamases:
1. Classification:
Beta-lactamases are classified into four main classes: A, B, C, and D, based on their amino acid sequences, biochemical properties, and substrate profiles.
2. Mechanisms of Action:
Class A:, These enzymes use a serine residue to hydrolyse the beta-lactam ring.
Class B (Metallo-beta-lactamases):, They use zinc ions for catalysis.
Class C: ,These are also known as AmpC beta-lactamases and are less commonly associated with resistance to extended-spectrum cephalosporins.
Class D: ,These enzymes are also known as OXA-type beta-lactamases.
,3. Clinical Significance:,
Beta-lactamases are a significant cause of antibiotic resistance, leading to treatment failures and increased morbidity and mortality.
Literature:
Bush, K., & Bradford, P. A. (2020). Interplay between β-lactamases and new β- lactamase inhibitors. Nature Reviews Microbiology, 18(3), 175-186.
Drawz, S. M., & Bonomo, R. A. (2010). Three decades of beta-lactamase inhibitors. Clinical Microbiology Reviews, 23(1), 160-201.
Livermore, D. M. (1995). Beta-lactamases in laboratory and clinical resistance. Clinical Microbiology Reviews, 8(4), 557-584.
Ambler, R. P. (1980). The structure of beta-lactamases. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 289(1036), 321-331.
Bebrone, C. (2007). Metallo-β-lactamases (classification, activity, genetic organization, structure, zinc coordination) and their superfamily. Biochemical Pharmacology, 74(12), 1686-1701.
Patel, G. (2005). Bonomo. G., Storm, D. R., & Bonomo, R. A. (Eds.). β-Lactamases: Evolution, Function, and Inhibition. Springer Science & Business Media.