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BETALACTAMASES

BETALACTAMASES

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Published by Saba Tariq

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Published by: Saba Tariq on Oct 07, 2011
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03/29/2015

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ß-Lactamases

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In β – Lactamases. The major difference between β – Lactamases and PBPs is in the rate of deacylation. 2 .Lactam Resistance.    PBPs and β – Lactamases are proteins which disrupt the β – Lactam bond to form an acyl-enzyme complex.Resistance Due to Destruction or Inactivation of a Drug β . a water molecule serves as the attacking nucleophile in the deacylation step.

• β – Lactamases are a heterogeneous group with structural similarities. • Classification: • Ambler Classification.Resistance Due to Destruction or Inactivation of a Drug β . D Groups (Serine β – Lactamases ) • B Group (Metallo-β – Lactamases ) • Bush-Jacoby-Medeiros Classification. C.Lactam Resistance. • Classification according to functional similarities. There are 4 Groups and many sub-groups. • A. 3 .

Resistant to CA. Carbapenem Not attacked Staphylococcal enzyme Broad Spectrum TEM1. TEM2. SHV1 ESBL Inhibitor Resistant TEM Carbenicillin hydrolyzing Cephalosporinases Inhibited by CA Carbapenemases Inhibited by CA 2a 2b 2be 2br 2c 2e 2f A A A A A A A 2d Group 3 3a 3b 3c Group 4 D B (Metalloenzyme) B (Metalloenzyme) B (Metalloenzyme) Cloxacillin Hydrolyzing Zinc dependent Carbapenemases 4 Not classified Miscellaneous Enzymes .Bush-Jacoby-Medeiros classification Group 1 (Cephalosporinases) Group 2 (Penicillinases) Major Subgroup Ambler Classification C (Cephalosporinases) Main Attributes Chromosomal.

 β – Lactamases are chromosomal.Lactam Resistance.Resistance Due to Destruction or Inactivation of a Drug β .  They may be constitutive or inducible.  They are secreted: In the periplasmic space in Gram Negative organisms and  In to the surrounding by Gram Positive organisms  5 . plasmid or transposon mediated.

 ESBL mutation renders the enzyme susceptible to inhibitors (Clav Acid.Resistance Due to Destruction or Inactivation of a Drug Class A β . Sulbactam. Tazobactam)  There are many non-TEM and non-SHV class A ESBL 6 .Lactamases  Two common class A (BJM Group 2) β – Lactamases are TEM-1 and SHV-1 found in Enterobacteriaceae  They are Penicillanases. No Cephalosporinase activity  They are progenitors of ESBL.

 They are close in amino acid sequence to Cephalosporinases of K oxytoca and P vulgaris.Lactamases  There are many non-TEM and non-SHV class A ESBL  Two important families are CTX-M and PER.  Carbapenems are quite stable to class A β Lactamases 7 .  This class of ESBL hydrolyze CTX and CRO better than CAZ and Tazobactam is better inhibitor than Clav Acid.Resistance Due to Destruction or Inactivation of a Drug Class A β .

Lactamases  These (BJM Group 3) are so called Metalloenzymes as they need Zn or some other metal for their activity and they are inhibited by chelators.  Carbapenems and Cephamycins are hydrolyzed.Resistance Due to Destruction or Inactivation of a Drug Class B β . B3.  Class B β . Tazobactam) are not effective.  Inhibitors (Clav Acid.  Although the genes encoding their production are not identical.Lactamases are subdivided in to three subgroups B1.Lactamases show very similar structure  Class B β – Lactamases are chromosomally encoded and their expression may be constitutive or inducible. B2. Sulbactam. 8 . these Class B β .

Lactamases  These (BJM Group 1) are produced by almost all Gram negative bacteria. In the event of high levels of cell wall degradation products. Tazobactam) are not effective. Sulbactam.  Class C β – Lactamases are chromosomally encoded and they are Cephalosporinases.Resistance Due to Destruction or Inactivation of a Drug Class C β .  Inhibitors (Clav Acid.  Repression and activation are closely related to cell wall synthesis. 9 . the repressor is repressed.  The encoding genes are carried on a plasmid and they are of four types.

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