Beta-lactamase

β -lactamases are enzymes produced by a number of bacteria. Hydrolysing a common structural component of the β -lactam antibiotics, the β -lactam ring, thereby preventing the effect of these drugs. Depending on the starting point, a distinction between penicillinases, cephalosporinases and carbapenemases. Therefore, β -lactamases play an important role in the dreaded antibiotic resistance of bacteria. The genetic information for the synthesis of β -lactamases is both chromosomally and plasmidisch inherited.

Catalyzed reaction

A β -lactamase catalyzed hydrolytic opening of the lactam ring of four β -lactam antibiotics:

The ring -opening product decarboxylated usually spontaneously. The irreversible binding of ring-opening products of endogenous proteins can cause allergic reactions. The result is a complete antigen that is recognized by the immune system of the body as a foreign protein and corresponding defense mechanisms in motion. This results in a sensitization, which can cause allergic reactions. Allergic reactions can range from mild skin eruptions to anaphylactic shock.

Classification

By now widely accepted has the molecular classification to Ambler, which is also relatively simple and catchy:

There is also a functional classification frequently used by Bush and Jacoby, which is based on the respective substrate spectrum.

Examples

Extended-spectrum β -lactamases (ESBL, class A)

Extended-spectrum β -lactamases, however, can cleave a larger (extended ) range of β -lactam -containing antibiotics. By a point mutation in the β -lactamase genes expressing bacteria such modified genes are capable of producing the extended-spectrum β -lactamase. The genes for ESBL located on plasmids that can be passed from bacterium to bacterium. ESBL -producing bacteria are resistant to penicillins, cephalosporins ( generation 1-4) and against monobactams. Mainly E. coli and Klebsiella (Gram -negative bacteria) carry ESBL genes.

In severe infections agents are choosing only carbapenems, tigecycline or colistin.

Carbapenemases

Carbapenemases are β -lactamases, which can cleave next to penicillins and cephalosporins and carbapenems. Of these enzymes, a number of variants of Gammaproteobacteria and Bacteroidetes is known. In 1998, 18 patients died in a New York hospital of Klebsiella carrying the carbapenemase KPC -2.

NDM -1 (Class B)

NDM -1, complete: New Delhi metallo -beta- lactamase, is the name for both a special carbapenemase as well as for the gene expressing this enzyme in bacteria. An extensive media coverage arose when that was mainly in India and Pakistan spread NDM -1 in the enterobacteria Escherichia coli and Klebsiella pneumoniae discovered in a British hospital. Previous cases in the UK, the Netherlands, Australia and Sweden resulted in part from operations (esp. plastic surgery ) in the former Asian countries. All bacteria have the genetic information of NDM -1, can not be effectively tackled as a multi-resistant pathogens with virtually all known antibiotics. Even the otherwise provided in medicine for emergencies bacterial infections carbapenems were found to sometimes be ineffective, since they can be cleaved by some β -lactamases. Only tigecycline and colistin are consistently effective.

NDM -2 ( Class B)

NDM- 2, the first version of the NDM -1 was first detected in Germany (Bochum) in 2011 in a case report of a patient from an Egyptian hospital. With the sequencing of the pathogen ( Acinetobacter baumannii ) with primers for NDM -1 was a point mutation ( position 82 ) found that an amino acid substitution (proline → alanine) has the protein result.

Proof

To β -lactamases easy to photometric demonstrate the nitrocefin was developed as a cephalosporin -like compound, because the nitrocefin changes color upon cleavage by the β -lactamases from yellow to red. The optimal wavelength for the measurement is approximately 486 nm