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Gene Review

bla  -  beta-lactamase

Escherichia coli

 
 
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Disease relevance of bla

  • Wild-type SHV-1 and -5 beta-lactamases and their respective Asn276-->Asp mutants were expressed under isogenic conditions by cloning the respective bla genes into the pBCSK(+) plasmid and transforming Escherichia coli DH5alpha [1].
  • Expression of Aeromonas caviae bla genes in Escherichia coli [2].
  • Analysis of beta-lactamase content by isoelectric focusing, PCR assays specific for various bla genes, and DNA sequencing showed that the strain produced TEM-1, a Citrobacter freundii AmpC-related cephalosporinase, and CTX-M-3 [3].
  • From now on, as the bla gene sequences of the most frequent Raoultella and Klebsiella species are available, the bla gene amplification method can be used to differentiate these species from each other, which the biochemical tests currently carried out in the clinical laboratory are unable to do [4].
  • Salmonella typhimurium JMC isolated in Argentina harbors a bla gene located on a plasmid (pMVP-5) which confers transferable resistance to oxyiminocephalosporins, aztreonam, and ceftibuten [5].
 

High impact information on bla

  • Cytosolic intermediates of murein biosynthesis and degradation thus act antagonistically to control beta-lactamase expression, thereby operating as a cell-wall sensing device [6].
  • Addition of the muropeptide, anhMurNAc-tripeptide, which accumulates in beta-lactamase-overproducing mutants, counteracts the negative effect of UDP-MurNAc-pentapeptide, restoring the innate ability of AmpR to induce ampC expression in vitro [6].
  • Shortening of bla transcripts by internal deletion or replacement of the 3' end with the corresponding segment of the ompA transcript had little effect on bla mRNA stability [7].
  • The primary translation products predicted on the basis of the plasmid constructions were hybrid proteins starting with beta-lactamase or phage MS2 polymerase information followed by the total preinterferon [8].
  • The analysis of hybrids between e(P4) and beta-lactamase demonstrated that a domain of e(P4) near its NH2' terminus was required for its function in hemin use [9].
 

Chemical compound and disease context of bla

  • A mirror-repeat polypurine-polypyrimidine sequence inserted between the E. coli beta-lactamase gene (conferring ampicillin resistance) and its bla promoter strongly inhibited transcription of the beta-lactamase gene in vivo [10].
  • The plasmid plP1066, harboured by by a methicillin-resistant Staphylococcus aureus strain isolated in France, carries genes specifying beta-lactamase [11].
  • A novel natural TEM beta-lactamase with extended-spectrum activity, TEM-138, was identified in a ceftazidime-resistant clinical isolate of Salmonella enterica serovar Infantis [12].
  • The chromosomally encoded beta-lactamase gene of Klebsiella oxytoca E23004, a strain resistant to cefoperazone and aztreonam, was cloned and expressed in Escherichia coli HB101 [13].
  • Recombinant expression in Escherichia coli suggested that bla1 ( LVS ) did not encode a functional beta-lactamase, whereas bla2 ( LVS ) encoded a functional beta-lactamase that hydrolyzed penicillins but was inactive against third-generation cephalosporins, including cefprozil [14].
 

Biological context of bla

 

Anatomical context of bla

  • Premature termination of translation at codon position 26 reduced the stability of both the translated and ribosome-free segments of bla mRNA, whereas release of ribosomes just 30 codons further downstream resulted in normal stability for both segments [19].
  • In cells grown at 24 degrees C the localization of beta-lactamase on the cell surface was almost quantitative (greater than 80% of the enzymatically active protein was exposed to the extracellular fluid) as determined by nitrocefin and penicillin G hydrolysis and trypsin accessibility [20].
  • Orientation of the hybrid protein with the OmpA signal peptide showed that the nuclease was translocated into the periplasm and the beta-lactamase remained in the cytoplasm [21].
  • Cells producing translocated forms of beta-lactamase can be directly selected as ampicillin-resistant colonies, and consequently a beta-lactamase fusion approach can be used for positive selection for export signals, and for rapid assessment of whether any protein expressed in Escherichia coli inserts into the bacterial cytoplasmic membrane [22].
  • The calculated biophysical properties and computed discriminant scores (predictive of importability of signal peptides into mammalian microsomes) of the kinetoplastid signal sequences nevertheless are similar to those of ppalphaMF and Escherichia coli beta-lactamase both of which were imported [23].
 

Associations of bla with chemical compounds

  • The expression of the inserted foreign gene (bla) encoding TEM beta-lactamase (Bla), can be induced by the addition of sucrose to the medium [24].
  • These results indicate that the increase in beta-lactamase synthesis caused by lincomycin is due to an increase in the stability of bla mRNA rather than activation of its synthesis [25].
  • We characterized the reversion of the mutant bla gene by a number of mutagens and in different genetic backgrounds and demonstrated that full ampicillin resistance can be restored only by a G-C-to-T-A transversion occurring at the first base of the codon [26].
  • Oligonucleotide-directed mutagenesis of the beta-lactamase gene, bla, on pBR322 was used to change the codon for the active-site serine 70, AGC, to CGC, coding for arginine [26].
  • It encoded a clavulanic acid-inhibited Ambler class A beta-lactamase, GIL-1, with a pI value of 7.5 and a molecular mass of ca. 29 kDa [27].
 

Other interactions of bla

  • Examination of the other three bla(CTX-M) genes by cloning, sequencing, and PCR analysis revealed the presence of a complex sul1-type integron that includes open reading frame ORF513, which carries the bla gene and the surrounding DNA [28].
  • The nucleotide sequences of Tn1 and Tn2 were determined over a 1,195-base-pair segment constituting most of the sequences of the tnpR and bla genes and the intervening region [29].
  • Further, a DNA fragment (bla) coding mature beta-lactamase was joined to the region coding the C terminus of the pre-S2 repeat to stabilize the gene product [30].
  • Deletion analyses revealed that the mini-F segment responsible for the inhibition of both processes was the promoter region of the sopA gene which had been cloned into a site upstream of the bla gene on pBR322 in such an orientation as to cause overexpression of bla [31].
  • Plasmid pBR322, as well as its delta rom and delta bla derivatives, were lost from their host within 60 generations, but a number of delta tet derivatives were quite stable under the same conditions [32].
 

Analytical, diagnostic and therapeutic context of bla

  • 9. The corresponding bla gene was identified by PCR and sequencing as a bla(TEM) gene [33].
  • ESBLs were characterized by isoelectric focusing; multiplex PCR for bla genes of the SHV, TEM and CTX-M families; and DNA sequencing [34].
  • The bla gene was transferable to Escherichia coli by electroporation of plasmid DNA [35].
  • Furthermore, inspection of the complexes by electron microscopy confirms that at r greater than 2, the bla promoter can bind specifically a second RNAP particle, as compared to the 1:1 complex observed at r less than or equal to 2 [36].
  • The expression of the bla gene carried on the plasmid was not affected by DNA titration or the addition of Ala [37].

References

  1. Aspartic acid for asparagine substitution at position 276 reduces susceptibility to mechanism-based inhibitors in SHV-1 and SHV-5 beta-lactamases. Giakkoupi, P., Tzelepi, E., Legakis, N.J., Tzouvelekis, L.S. J. Antimicrob. Chemother. (1999) [Pubmed]
  2. Expression of Aeromonas caviae bla genes in Escherichia coli. Sayeed, S., Saunders, J.R., Edwards, C., Corkill, J.E., Hart, C.A. J. Antimicrob. Chemother. (1996) [Pubmed]
  3. CTX-m-3 beta-lactamase-producing Escherichia coli from Greece. Mavroidi, A., Tzelepi, E., Miriagou, V., Gianneli, D., Legakis, N.J., Tzouvelekis, L.S. Microb. Drug Resist. (2002) [Pubmed]
  4. Genetic and biochemical characterization of the chromosomal class A beta-lactamases of Raoultella (formerly Klebsiella) planticola and Raoultella ornithinolytica. Walckenaer, E., Poirel, L., Leflon-Guibout, V., Nordmann, P., Nicolas-Chanoine, M.H. Antimicrob. Agents Chemother. (2004) [Pubmed]
  5. Characterization of beta-lactamase gene blaPER-2, which encodes an extended-spectrum class A beta-lactamase. Bauernfeind, A., Stemplinger, I., Jungwirth, R., Mangold, P., Amann, S., Akalin, E., Anğ, O., Bal, C., Casellas, J.M. Antimicrob. Agents Chemother. (1996) [Pubmed]
  6. Cytosolic intermediates for cell wall biosynthesis and degradation control inducible beta-lactam resistance in gram-negative bacteria. Jacobs, C., Frère, J.M., Normark, S. Cell (1997) [Pubmed]
  7. The stability of E. coli gene transcripts is dependent on determinants localized to specific mRNA segments. Belasco, J.G., Nilsson, G., von Gabain, A., Cohen, S.N. Cell (1986) [Pubmed]
  8. Expression of human fibroblast interferon gene in Escherichia coli. Derynck, R., Remaut, E., Saman, E., Stanssens, P., De Clercq, E., Content, J., Fiers, W. Nature (1980) [Pubmed]
  9. Lipoprotein e(P4) is essential for hemin uptake by Haemophilus influenzae. Reidl, J., Mekalanos, J.J. J. Exp. Med. (1996) [Pubmed]
  10. Triple-helix specific ligands stabilize H-DNA conformation. Duval-Valentin, G., de Bizemont, T., Takasugi, M., Mergny, J.L., Bisagni, E., Hélène, C. J. Mol. Biol. (1995) [Pubmed]
  11. Rearrangements in the staphylococcal beta-lactamase-encoding plasmid, pIP1066, including a DNA inversion that generates two alternative transposons. Derbise, A., Dyke, K.G., el Solh, N. Mol. Microbiol. (1995) [Pubmed]
  12. A novel extended-spectrum TEM-type beta-lactamase, TEM-138, from Salmonella enterica serovar Infantis. Chouchani, C., Berlemont, R., Masmoudi, A., Galleni, M., Frere, J.M., Belhadj, O., Ben-Mahrez, K. Antimicrob. Agents Chemother. (2006) [Pubmed]
  13. Chromosomal beta-lactamase of Klebsiella oxytoca, a new class A enzyme that hydrolyzes broad-spectrum beta-lactam antibiotics. Arakawa, Y., Ohta, M., Kido, N., Mori, M., Ito, H., Komatsu, T., Fujii, Y., Kato, N. Antimicrob. Agents Chemother. (1989) [Pubmed]
  14. The Bla2 beta-lactamase from the live-vaccine strain of Francisella tularensis encodes a functional protein that is only active against penicillin-class beta-lactam antibiotics. Bina, X.R., Wang, C., Miller, M.A., Bina, J.E. Arch. Microbiol. (2006) [Pubmed]
  15. Inhibitor-resistant TEM (IRT) beta-lactamases with different substitutions at position 244. Bret, L., Chaibi, E.B., Chanal-Claris, C., Sirot, D., Labia, R., Sirot, J. Antimicrob. Agents Chemother. (1997) [Pubmed]
  16. Impact of gyrA and parC mutations on quinolone resistance, doubling time, and supercoiling degree of Escherichia coli. Bagel, S., Hüllen, V., Wiedemann, B., Heisig, P. Antimicrob. Agents Chemother. (1999) [Pubmed]
  17. Beta-lactamase expression in Streptomyces cacaoi. Urabe, H., Lenzini, M.V., Mukaide, M., Dusart, J., Nakano, M.M., Ghuysen, J.M., Ogawara, H. J. Bacteriol. (1990) [Pubmed]
  18. Specific inhibition of transcription by triple helix-forming oligonucleotides. Duval-Valentin, G., Thuong, N.T., Hélène, C. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  19. Effect of premature termination of translation on mRNA stability depends on the site of ribosome release. Nilsson, G., Belasco, J.G., Cohen, S.N., von Gabain, A. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  20. Transport and anchoring of beta-lactamase to the external surface of Escherichia coli. Francisco, J.A., Earhart, C.F., Georgiou, G. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  21. Reversible topology of a bifunctional transmembrane protein depends upon the charge balance around its transmembrane domain. Kim, H., Paul, S., Gennity, J., Jennity J [corrected to Gennity, J., Inouye, M. Mol. Microbiol. (1994) [Pubmed]
  22. Beta-lactamase as a probe of membrane protein assembly and protein export. Broome-Smith, J.K., Tadayyon, M., Zhang, Y. Mol. Microbiol. (1990) [Pubmed]
  23. Species-specificity in endoplasmic reticulum signal peptide utilization revealed by proteins from Trypanosoma brucei and Leishmania. Al-Qahtani, A., Teilhet, M., Mensa-Wilmot, K. Biochem. J. (1998) [Pubmed]
  24. Development of an inducible and enhancible expression and secretion system in Bacillus subtilis. Wong, S.L. Gene (1989) [Pubmed]
  25. Lincomycin increases the half-life of beta-lactamase mRNA. Matsushita, O., Okabe, A., Hayashi, H., Kanemasa, Y. Antimicrob. Agents Chemother. (1989) [Pubmed]
  26. Creation of a test plasmid for detecting G-C-to-T-A transversions by changing serine to arginine in the active site of beta-lactamase. Foster, P.L., Dalbadie-McFarland, G., Davis, E.F., Schultz, S.C., Richards, J.H. J. Bacteriol. (1987) [Pubmed]
  27. Chromosome-Encoded Narrow-Spectrum Ambler Class A {beta}-Lactamase GIL-1 from Citrobacter gillenii. Naas, T., Aubert, D., Ozcan, A., Nordmann, P. Antimicrob. Agents Chemother. (2007) [Pubmed]
  28. Dissemination of CTX-M-type beta-lactamases among clinical isolates of Enterobacteriaceae in Paris, France. Eckert, C., Gautier, V., Saladin-Allard, M., Hidri, N., Verdet, C., Ould-Hocine, Z., Barnaud, G., Delisle, F., Rossier, A., Lambert, T., Philippon, A., Arlet, G. Antimicrob. Agents Chemother. (2004) [Pubmed]
  29. Variations between the nucleotide sequences of Tn1, Tn2, and Tn3 and expression of beta-lactamase in Pseudomonas aeruginosa and Escherichia coli. Chen, S.T., Clowes, R.C. J. Bacteriol. (1987) [Pubmed]
  30. Production and secretion in Escherichia coli of hepatitis B virus pre-S2 antigen as fusion proteins with beta-lactamase. Kadokura, H., Yoda, K., Imai, M., Yamasaki, M. Appl. Environ. Microbiol. (1990) [Pubmed]
  31. Inhibition of cell growth and stable DNA replication by overexpression of the bla gene of plasmid pBR322 in Escherichia coli. Katayama, T., Nagata, T. Mol. Gen. Genet. (1990) [Pubmed]
  32. Stability of pBR322-derived plasmids. Chiang, C.S., Bremer, H. Plasmid (1988) [Pubmed]
  33. TEM-109 (CMT-5), a natural complex mutant of TEM-1 beta-lactamase combining the amino acid substitutions of TEM-6 and TEM-33 (IRT-5). Robin, F., Delmas, J., Chanal, C., Sirot, D., Sirot, J., Bonnet, R. Antimicrob. Agents Chemother. (2005) [Pubmed]
  34. In vitro activity of temocillin against extended spectrum beta-lactamase-producing Escherichia coli. Rodriguez-Villalobos, H., Malaviolle, V., Frankard, J., de Mendonça, R., Nonhoff, C., Struelens, M.J. J. Antimicrob. Chemother. (2006) [Pubmed]
  35. Characterization of SFO-1, a plasmid-mediated inducible class A beta-lactamase from Enterobacter cloacae. Matsumoto, Y., Inoue, M. Antimicrob. Agents Chemother. (1999) [Pubmed]
  36. A second RNA-polymerase can bind specifically to the bla promoter of Tn3, repressing transcription initiation. Duval-Valentin, G., Schmitt, B., Ehrlich, R. Nucleic Acids Res. (1988) [Pubmed]
  37. Regulation of in vitro expression of the Escherichia coli frd operon: alanine and Fnr represent positive and negative control elements. Latour, D.J., Weiner, J.H. Nucleic Acids Res. (1988) [Pubmed]
 
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