bètalactamases

Bètalactamases are enzymes produced by bacteria that hydrolyze the beta-lactam ring of beta-lactam antibiotics, rendering drugs such as penicillins and cephalosporins ineffective. They are a major mechanism of antibiotic resistance in many Gram-negative and some Gram-positive species and can be encoded on chromosomes or mobile genetic elements, enabling rapid spread.

The Ambler classification groups beta-lactamases into four classes (A through D) based on amino acid sequence. Class B enzymes are metallo-beta-lactamases that require zinc for activity. Classes A, C and D are serine beta-lactamases. Some enzymes have expanded activity, termed extended-spectrum beta-lactamases (ESBLs) that hydrolyze third-generation cephalosporins, and carbapenemases that can inactivate carbapenems. Notable examples include TEM, SHV and CTX-M (ESBLs), and KPC, VIM, NDM, IMP and OXA-type carbapenemases.

Genes encoding bètalactamases are commonly carried on plasmids and other mobile elements, enabling rapid spread between bacteria. ESBLs and AmpC enzymes expand resistance within Enterobacterales; carbapenemases such as KPC, NDM, VIM/IMP, and OXA-48-like enzymes are a major clinical concern in hospitals, limiting treatment options.

Detection and clinical management rely on phenotypic screening and molecular tests to identify the specific enzyme and resistance level. Treatment often combines a beta-lactam antibiotic with a beta-lactamase inhibitor (for example, clavulanate, tazobactam, or newer inhibitors such as avibactam, relebactam, and vaborbactam). However, many metallo-beta-lactamases and certain OXA enzymes are poorly inhibited by older drugs, complicating therapy. Infections require stewardship and infection-control measures to prevent spread.

Public health significance: beta-lactamases drive multidrug-resistant infections and are a focus of surveillance, research, and novel inhibitor development. Ongoing efforts aim to limit dissemination, improve rapid diagnostics, and expand therapeutic options.