Related Experiment Video
Updated: Jul 22, 2026
09:01
Mutagenesis and Functional Selection Protocols for Directed Evolution of Proteins in E. coli
Published on: March 16, 2011
Evolution of beta-lactamase inhibitors.
1Chemotherapeutic Research Centre, Brockham Park, Betchworth, Surrey, United Kingdom.
Reviews of Infectious Diseases
|July 1, 1991
Summary
Beta-lactamase inhibitors combat bacterial resistance to antibiotics. Early research failed, but screening microorganisms led to discovering clavulanic acid, now clinically used with amoxicillin and ticarcillin.
Area of Science:
- Microbiology
- Pharmacology
Background:
- Bacterial resistance to beta-lactam antibiotics is primarily mediated by beta-lactamase production.
- Early attempts to develop beta-lactamase inhibitors were unsuccessful.
- Some semisynthetic penicillins showed inhibitory potential but lacked clinical application.
Purpose of the Study:
- To identify naturally occurring inhibitors of beta-lactamase from microorganisms.
- To develop effective agents against bacterial resistance to beta-lactam antibiotics.
Main Methods:
- Screening of microorganisms for beta-lactamase inhibitory compounds.
- Discovery and development of natural beta-lactamase inhibitors.
Main Results:
- The screening program led to the discovery of olivanic acids and clavulanic acid.
- Clavulanic acid was formulated with amoxicillin and ticarcillin, becoming clinically available in 1981.
- Subsequent development yielded other inhibitors like sulbactam and tazobactam.
Conclusions:
- Clavulanic acid represents a significant advancement in combating bacterial resistance.
- Ongoing development of beta-lactamase inhibitors like sulbactam and tazobactam continues.
- The clinical utility and advantages of newer inhibitors over clavulanate require further evaluation.
Related Concept Videos
00:57Antibiotic Selection
Overview
01:27Combined Effects of Drugs: Synergism
Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Such synergistic combinations...
01:30Development of Antibiotic Resistance
Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
01:25Mechanism of Antibiotic Resistance in MRSA
Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and acquisition...
01:23Inhibitors of Gram-positive Cell Wall Synthesis
Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
01:25Clinical Significance of Antibiotic Resistance
Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...