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Beta-lactamase Knowledge

Beta-lactamase Knowledge

 

Beta-lactamases, or β-lactamases, are enzymes which are produced by bacteria. Bacteria can benefit from them by obtaining multi-resistance to β-lactam antibiotics which include penicillins, cephamycins, and carbapenems (ertapenem).

 

β-lactam is a four-atom ring structure, and is shared by the β-lactam antibiotics. Through hydrolysis, β-lactamases break the β-lactam ring open, deactivating the molecule's antibacterial properties. And thus provides the resistance against β-lactam antibiotics.

 

β-lactam antibiotics are typically used to treat a broad spectrum of Gram-positive and Gram-negative bacteria. The Gram-negative organisms usually secreted the β-lactamases especially when antibiotics are present in the environment.

One of the most famous β-lactamases is penicillinase, it is a specific type of β-lactamase, showing specificity for penicillins. Penicillinase was isolated even earlier that the clinical use of penicillin. Penicillinase production quickly spread to bacteria that previously did not produce it or produced it only rarely. Penicillinase-resistant beta-lactams such as methicillin were developed, but there is now widespread resistance to even these.

Detection
Beta-lactamase enzymatic activity can be detected using nitrocefin, a chromogenic cephalosporin substrate which changes color from yellow to red upon beta-lactamase mediated hydrolysis.

Evolution
Beta-lactamases are ancient bacterial enzymes. The class B beta-lactamases (the metallo-beta-lactamases) are divided into three subclasses: B1, B2 and B3. Subclasses B1 and B2 are theorized to have evolved about one billion years ago and subclass B3s is theorized to have evolved before the divergence of the Gram-positive and Gram-negative eubacteria about two billion years ago.

The other three groups are serine enzymes that show little homology to each other. Structural studies have shown that groups A and D are sister taxa and that group C diverged before A and D.[26] These serine-based enzymes, like the group B betalactamases, are of ancient origin and are theorized to have evolved about two billion years ago.

The OXA group (in class D) in particular is theorized to have evolved on chromosomes and moved to plasmids on at least two separate occasions.

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