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Past and Present Perspectives on β-Lactamases
Past and Present Perspectives on β-Lactamases
- Publication Year :
- 2018
- Publisher :
- American Society for Microbiology, 2018.
-
Abstract
- β-Lactamases, the major resistance determinant for β-lactam antibiotics in Gram-negative bacteria, are ancient enzymes whose origins can be traced back millions of years ago. These well-studied enzymes, currently numbering almost 2,800 unique proteins, initially emerged from environmental sources, most likely to protect a producing bacterium from attack by naturally occurring β-lactams. Their ancestors were presumably penicillin-binding proteins that share sequence homology with β-lactamases possessing an active-site serine. Metallo-β-lactamases also exist, with one or two catalytically functional zinc ions. Although penicillinases in Gram-positive bacteria were reported shortly after penicillin was introduced clinically, transmissible β-lactamases that could hydrolyze recently approved cephalosporins, monobactams, and carbapenems later became important in Gram-negative pathogens. Nomenclature is based on one of two major systems. Originally, functional classifications were used, based on substrate and inhibitor profiles. A later scheme classifies β-lactamases according to amino acid sequences, resulting in class A, B, C, and D enzymes. A more recent nomenclature combines the molecular and biochemical classifications into 17 functional groups that describe most β-lactamases. Some of the most problematic enzymes in the clinical community include extended-spectrum β-lactamases (ESBLs) and the serine and metallo-carbapenemases, all of which are at least partially addressed with new β-lactamase inhibitor combinations. New enzyme variants continue to be described, partly because of the ease of obtaining sequence data from whole-genome sequencing studies. Often, these new enzymes are devoid of any phenotypic descriptions, making it more difficult for clinicians and antibiotic researchers to address new challenges that may be posed by unusual β-lactamases.
- Subjects :
- 0301 basic medicine
Gram-negative bacteria
medicine.drug_class
030106 microbiology
Antibiotics
Gram-Positive Bacteria
beta-Lactams
beta-Lactamases
Serine
03 medical and health sciences
Bacterial Proteins
Gram-Negative Bacteria
medicine
Pharmacology (medical)
Monobactams
Pharmacology
Genetics
chemistry.chemical_classification
biology
Penicillinase
biology.organism_classification
Amino acid
Cephalosporins
Penicillin
Infectious Diseases
Enzyme
chemistry
Minireview
Bacteria
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....7102526e91798f6efa01da7288adf3f7