ß-lactams belong to a family of antibiotics which is characterized by a ß-lactam
ring. Penicillins, cephalosporins, clavams (or oxapenams), cephamycins and carbapenems
are members of this family. The integrity of the ß-lactam ring is necessary
for the activity which results in the inactivation of a set of transpeptidases that
catalyze the final cross-linking reactions of peptidoglycan synthesis.
Resistance to ß-lactams in clinical isolates is primarily due to the hydrolysis of the antibiotic by a ß-lactamase. Mutational events resulting in the modification of PBPs (penicillin binding proteins) or cellular permeability can also lead to ß-lactam resistance.
ß-lactamases constitute a heterogenous group of enzymes. Several classification schemes have been proposed according to their hydrolytic spectrum, susceptibility to inhibitors, genetic localisation (plasmidic or chromosomal), gene or amino-acid protein sequence. The functional classification scheme of ß-lactamases proposed by Bush, Jacoby and Medeiros (1995) defines four groups according to their substrate and inhibitor profiles. Group 1 are cephalosporinases that are not well inhibited by clavulanic acid; group 2 penicillinases, cephalosporinases, and broad-spectrum ß-lactamases that are generally inhibited by active site-directed ß-lactamase inhibitors; group 3 metallo-ß-lactamases that hydrolyze penicillins, cephalosporins, and carbapenems and that are poorly inhibited by almost all ß-lactam-containing molecules; group 4 penicillinases that are not well inhibited by clavulanic acid. Subgroups were also defined according to rates of hydrolysis of carbenicillin or cloxacillin (oxacillin) by group 2 penicillinases. The classification initially introduced by Ambler (1980) and based on the amino-acid sequence recognizes four molecular classes designated A to D. Classes A, C, and D gather evolutionarily distinct groups of serine enzymes, and class B the zinc-dependent ("EDTA-inhibited") enzymes.
Fonzé, E., P. Charlier, Y. To'th, M. Vermeire, X. Raquet, A. Dubus, and J-M. Frère. 1995. TEM1 beta-lactamase structure solved by molecular replacement and refined structure of the S235A mutant. Acta Cryst. 51:682-694.
The bla gene encoding the TEM-1 ß-lactamase is the most encountered AmpR marker used in molecular biology (pBR and pUC plasmids). TEM-1 is a widespread plasmidic ß-lactamase that attacks narrow-spectrum cephalosporins, cefamandole, and cefoperazone and all the anti-gram-negative-bacterium penicillins except temocillin. Aminothiazol chephalosporins, cephamycins, monobactams and carbapenems are resistant to its action. It belongs to the Bush-Jacoby-Medeiros group 2b and the molecular class A. The TEM-1 enzyme was first reported from an E. coli isolate in 1965 and is now the commonest ß-lactamase found in enterobacteriaceae. Resistance in more than 50% of AmpR E. coli clinical isolates is due to TEM-1. Most extended-spectrum ß-lactamases (ESBLs) derive from TEM-1, TEM-2 and SHV-1 by mutations generating 1- to 4-amino-acid sequence substitutions.
acid sequences for TEM, SHV and OXA extended-spectrum ß-lactamases (Link
to the Lahey Clinic)
Is It Important to Identify Extended-Spectrum ß-Lactamase-Producing Isolates? (Copyrights © by WARN Development)
Penicillin-resistant pneumococci (Copyrights © by WARN Development)
Penicillin-resistant Streptococcus pneumoniae (Link to ENARE)
Methicillin-resistant staphylococci (Link to ENARE)
Penicillin derivatives (Copyrights © by Purdue Research Foundation)
Penicillins (link to the University of Winconsin Hospital)
Cephalosporin derivatives and related compounds (Copyrights © by Purdue Research Foundation)
Cephalosporins (link to the University of Winconsin Hospital)
Bush, K., G. A. Jacoby, and A. A. Medeiros. 1995. A functional classification scheme for ß-lactamases and its
correlation to molecular structure. Antimicrob. Agents Chemother. 39:1211-1233.
Review. No abstract available.
Bush, K., and G. Jacoby. 1997. Nomenclature of TEM ß-lactamases. J. Antimicrob. Chemother. 39:1-3. Review. No abstract available.
Frère, J. 1995. Beta-lactamases and bacterial resistance to antibiotics. Mol. Microbiol. 16:385-395. Review.
Ghuysen, J. M. 1991. Serine ß-lactamases and penicillin-binding proteins. Annu. Rev. Microbiol. 45:37-67. Review. No abstract available.
Ghuysen, J. M. 1994. Molecular structures of penicillin-binding proteins and ß-lactamases. Trends Microbiol. 2:372-379.
Jacoby, G. A. 1994. Extrachromosomal resistance in Gram-negative organisms: the evolution of ß-lactamase. Trends Microbiol. 2:357-360.
Livermore, D.M. 1995. ß-lactamases in laboratory and clinical resistance. Clin. Microbiol. Rev. 8:557-584. Review.
Medeiros, A. A. 1997. Evolution and dissemination of ß-lactamases accelerated by generations of ß-lactam antibiotics. Clin. Inf. Diseases. 24(Suppl 1):S19-S45. Review.
Matagne, A., J. Lamotte-Brasseur, and J.M. Frère. 1998. Catalytic properties of class A beta-lactamases: efficiency and diversity. Biochem. J. 330:581-598.
Massova, I., and S. Mobashery. 1998. Kinship and diversification of bacterial penicillin-binding proteins and ß-lactamases. Antimicrob. Agents Chemother. 42:1-17. Review. No abstract available.
Thomson, C. J., and S. G. B. Amyes. 1993. Molecular epidemiology of the plasmid encoded TEM-1 ß-lactamase in Scotland. Epidemiol. Infect. 110:117-125.
Thomson, C. J., P. M. Shanahan, and S. G. B. Amyes. 1994. TEM-1 plasmids in the community. Lancet 343:921. Letter. No abstract available.