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TEM-1 beta-lactamase is a **Class A serine hydrolase enzyme** produced primarily by Gram-negative bacteria such as *Escherichia coli* and *Klebsiella pneumoniae* that acts by hydrolyzing the beta-lactam ring of penicillin and early cephalosporin antibiotics, conferring bacterial resistance. Discovered in 1963, it is the most common beta-lactamase responsible for ampicillin resistance in *E. coli* and is widely distributed among Enterobacteriaceae and other pathogens. Over 170 variants of TEM-1 have evolved, expanding resistance to additional antibiotics (extended-spectrum beta-lactamases, ESBLs) through amino acid substitutions mostly around the active site loop, though original TEM-1 remains highly efficient against penicillins but less so against third-generation cephalosporins. Remediation of TEM-1-mediated resistance involves the clinical use of beta-lactamase inhibitors (such as clavulanic acid), though continued mutation poses a challenge to therapy.
Enzymatic hydrolysis of the beta-lactam ring in antibiotics, rendering them inactive
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