Beta-lactamase class A and class C (Class A β-lactamase (often abbreviated as Class A BL) and class C β-lactamase (Class C BL); there is no single unified abbreviation for both classes together.)

Molecular Classification

Enzyme, Hydrolase, Antibiotic resistance enzyme, Serine hydrolase (A and C both use active site serine), Beta-lactamase

Other Names

Class A serine β-lactamase, Class C serine β-lactamase, Serine β-lactamase (encompassing A, C, and D), Penicillinase (for some Class A enzymes), Cephalosporinase (for many Class C enzymes), ESBL (Extended-spectrum beta-lactamase, often for Class A variants like TEM, SHV, CTX-M)

Disease Roles

Infection (bacterial): Major contributor to bacterial resistance in infectious diseases, particularly in Gram-negative bacteriaIndirectly associated with treatment failure for infections due to antibiotic resistance

Beta-lactamase class A and class C Overview

Class A and class C beta-lactamases are two major molecular classes of enzymes produced by bacteria that confer resistance to beta-lactam antibiotics (including penicillins, cephalosporins, and related drugs). Both are serine hydrolases: they utilize an active site serine to break the characteristic four-membered beta-lactam ring of these antibiotics, disabling their antibacterial activity. Class A beta-lactamases include enzymes such as TEM, SHV, and CTX-M, many of which are plasmid-encoded, spread easily, and may confer extended-spectrum resistance (ESBLs). They are often inhibited by clavulanic acid but can evolve inhibitor resistance. Class C beta-lactamases (often called AmpC enzymes) are typically chromosomally encoded cephalosporinases that confer resistance primarily to cephalosporins and are often not inhibited by traditional beta-lactamase inhibitors. Both enzyme classes use a conserved mechanism involving acylation of a serine residue, followed by hydrolysis of the beta-lactam ring, and play a critical role in global antibiotic resistance in clinically important Gram-negative bacteria.

Mechanism of Action

Hydrolysis of beta-lactam ring: The enzyme attacks the amide bond of the beta-lactam ring, breaking antibiotic structure and inactivating antibacterial activity. Serine-based catalysis: Both A and C use a nucleophilic serine (Ser70) for acylation and breakdown of beta-lactam antibiotics.

Biological Functions

Antibiotic hydrolysis

Antibiotic resistance

Inactivation of beta-lactam antibiotics

Disease Associations

Infection (bacterial): Major contributor to bacterial resistance in infectious diseases, particularly in Gram-negative bacteria

Indirectly associated with treatment failure for infections due to antibiotic resistance

Safety Considerations

Therapeutic challenge: Rapid emergence of resistance renders many antibiotics ineffective
Cross-resistance: Transferable enzymes via plasmids can make outbreaks difficult to control
Detection limitations: Some class C enzymes (AmpC) are not inhibited by common beta-lactamase inhibitors, leading to potential misdiagnosis of resistance

Interacting Drugs

Beta-lactam antibiotics: Penicillins, cephalosporins, monobactams, carbapenems (hydrolyzed/inactivated by these enzymes, to varying extents)

Beta-lactamase inhibitors: Clavulanic acid, tazobactam, avibactam (some, especially class A, are inhibited; class C may be poorly inhibited by traditional inhibitors)

Associated Biomarkers

Biomarker
Presence of class A or class C beta-lactamase genes/proteins (via PCR, immunoassay, or activity assays) can serve as a biomarker for antibiotic resistance in clinical isolates
Substrate profile: Resistance to penicillins and cephalosporins, respectively, often indicates the presence of class A or C beta-lactamases