Family of Extended Spectrum Beta-Lactamases

Two main approaches are most often used to classify the group of beta lactamases: the Ambler molecular classification system and the Bush-Jacoby-Medieros functional classification system. In the ambler classification, beta lactamases are grouped into four class A,B,C and D. These classes are based on motifs made up of the main sequences that make up the protein molecules. Beta lactamases of classes A, C and D use a serine as an enzyme active center, whereas beta lactamases of class B use the metal zinc.

In Bush-Jacoby-Medeiros functional classification, beta lactamases are categorized into groups 1-3 based on how well they degrade beta lactam substrates and how well they are affected by inhibitors. ESBLs (Extended Spectrum Beta Lactamases) are included in subgroup 2be of the bush Jacoby categorization. The e in 2be indicates that the beta lactamases have an extended spectrum and the 2be designation indicates that these enzymes are derived from group 2b beta lactamases. These broad spectrum enzymes hydrolyze one or more oxyimino beta lactams, such as cefotaxime, ceftazidime and aztreonam, while also maintaining their activity against penicillins and cephalosporins of subgroup 2b beta lactamases. This classification approach takes into account lactamase inhibitors and lactam substrates that are clinically relevant, which makes it much more immediately applicable to a physician or microbiologist working in a diagnostic laboratory.

ESBLs are seen as harmful worldwide, especially in hospitalized patients. In certain places of the world, ESBLs are occurring more frequently. Patients infected with strains that produce ESBLs are considered high risk since therapy is no longer effective in these patients and infections have been linked to unfavourable results.

These are adaptable enzymes that have developed defence mechanisms against their inhibitors and developed an ability to counteract beta lactam antibiotics. As a result, it is imperative to recognize potential EBSLs variants and develop thoughtful policy actions to lessen their frequency. Considering the existing situation, it is extremely realistic to predict that beta lactamases and their classification system will be subject to constant change in the future.

References

1.Ghafourian S, Sadeghifard N, Soheili S, Sekawi Z. Extended Spectrum Beta-lactamases: Definition, Classification and Epidemiology. Curr Issues Mol Biol. 2015;17:11-21.

2.Castanheira M, Simner PJ, Bradford PA. Extended-spectrum β-lactamases: an update on their characteristics, epidemiology and detection. JAC Antimicrob Resist. 2021 Jul 16;3(3):dlab092. 

3.Bush K, Jacoby GA. Updated functional classification of beta-lactamases. Antimicrob Agents Chemother. 2010 Mar;54(3):969-76. 

4.Hall BG, Barlow M. Revised Ambler classification of {beta}-lactamases. J Antimicrob Chemother. 2005 Jun;55(6):1050-1.