This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cartelle, M.
Right arrow Articles by Bou, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cartelle, M.
Right arrow Articles by Bou, G.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, June 2004, p. 2308-2313, Vol. 48, No. 6
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.6.2308-2313.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

High-Level Resistance to Ceftazidime Conferred by a Novel Enzyme, CTX-M-32, Derived from CTX-M-1 through a Single Asp240-Gly Substitution

Monica Cartelle, Maria del Mar Tomas, Francisca Molina, Rita Moure, Rosa Villanueva, and German Bou*

Servicio de Microbiologia, Complejo Hospitalario Universitario Juan Canalejo, 15006 La Coruña, Spain

Received 27 June 2003/ Returned for modification 8 September 2003/ Accepted 13 February 2004


arrow
ABSTRACT
 
A clinical strain of Escherichia coli isolated from pleural liquid with high levels of resistance to cefotaxime, ceftazidime, and aztreonam harbors a novel CTX-M gene (blaCTX-M-32) whose amino acid sequence differs from that of CTX-M-1 by a single Asp240-Gly substitution. Moreover, by site-directed mutagenesis we demonstrated that this replacement is a key event in ceftazidime hydrolysis


arrow
TEXT
 
The emergence of plasmid-mediated extended-spectrum ß-lactamases in members of the family Enterobacteriaceae has become a worldwide problem (3, 4, 6, 7, 11-13, 16).

Most extended-spectrum ß-lactamases are derivatives of TEM-1, TEM-2, or SHV-1 enzymes; however, there are an increasing number of reports that describe the worldwide emergence of ß-lactamases belonging to other families, such as CTX-M and/or OXA derivatives (8).

The family of CTX-M enzymes is grouped on the basis of similarities in amino acid sequences into four major phylogenetic trees (6): the CTX-M-1 group (CTX-M-1 or MEN-1, CTX-M-3, CTX-M-10, CTX-M-12, CTX-M-15, and now CTX-M-32), the CTX-M-2 group (CTX-M-2, CTX-M-4, CTX-M-5, CTX-M-6, CTX-M-7, CTX-20, and Toho-1), the CTX-M-8 group, and the CTX-M-9 group (CTX-M-9, CTX-M-13, CTX-M-14, CTX-M-16, CTX-M-18, CTX-M-19, CTX-M-21, and Toho-2). The designation CTX-M refers to a potent activity against cefotaxime and having only a remnant of activity toward ceftazidime.

Here we report the molecular characterization of a new CTX-M ß-lactamase derived from CTX-M-1 through a single Asp240-Gly substitution, CTX-M-32. In addition, we report experimental data showing that substitution of this amino acid is itself sufficient to confer hydrolytic activity against ceftazidime.

Patterns of antibiotic susceptibility shown by the clinical strain E. coli JC19325, as well as its transconjugant and transformants, are shown in Table 1. The MICs were determined by E-test and interpreted according to the method of the National Committee for Clinical Laboratory Standards (18). The clinical strain JC19325 showed a high level of resistance to cefotaxime, ceftazidime, and aztreonam (MICs of >256 µg/ml), cefoxitin (MIC of >256 µg/ml), and cefepime (MIC of 64 µg/ml). Moreover, clavulanic acid acted synergistically with amoxicillin, cefotaxime, and ceftazidime (E-test; ABBiodisk, Solna, Sweden), thus indicating the presence of a class A ß-lactamase (9). An Escherichia coli TG1 transformant harboring the pMC-2 plasmid showed higher MICs of the affected antibiotics, probably due to more copies of the bla gene.


View this table:
[in this window]
[in a new window]
  		TABLE 1. MICs of ß-lactams for the JC19325 clinical strain, E. coli XL1(pMC-1), E. coli TG1, E. coli TG1(pMC-2), and E. coli TG1(pMC-3)

Isoelectric focusing was performed using polyacrylamide gels containing Ampholine, within a pH range of 3.5 to 9.5, as previously described (17). The clinical isolate produced one enzyme with a pI of 9.0.

In the present study the E. coli XL1-Blue MRF'Kan strain (Stratagene Europe, Amsterdam, The Netherlands) was used in the conjugation experiments.

The clinical strain JC19325 had one plasmid which harbored a ß-lactamase with a pI of 9.0 that was transferred by conjugation into E. coli XL1-Blue MRF'Kan using kanamycin (25 µg/ml) and cefotaxime (2 µg/ml) as selective antibiotics. A few of the transconjugants which grew harbored an identical plasmid of approximately 15 kb, which was named pMC-1.

Plasmid DNA was isolated by the alkaline lysis method (23) from the transconjugant that produced a single ß-lactamase with a pI of 9.0. Plasmid DNA was digested with KpnI and ligated to the plasmid vector pBGS18– (25); afterwards, the ligation mixture was introduced into E. coli TG1 cells by transformation with CaCl2, and transformants were detected on Luria-Bertani agar plates with cefotaxime (2 µg/ml) and kanamycin (25 µg/ml). The resulting plasmid, designated pMC-2, carried a bla-producing insert of size circa 4 kb. Double-stranded templates were subjected to nucleotide sequencing by using the method of Sanger et al. (23, 23a).

During isoelectric focusing, the pI 9.0 ß-lactamase activity band from the E. coli transformants cofocused with the ß-lactamase activity band from the clinical strain JC19325. Nucleotide sequencing of the KpnI insert revealed some interesting features, including (i) a new bla gene. This new bla gene was 876 bp long, initiated with an ATG codon, and ended with a TGA codon (291 amino acids long). The initiation codon was preceded by a Shine-Dalgarno ribosome-binding sequence, AAGGAA. The EMBL and Swiss-Prot database searches for this open reading frame revealed similarities to CTX-M ß-lactamases. The deduced amino acid sequence had the closest homology (99%) with the CTX-M-1 enzyme (2, 3), from which it differed by the single amino acid substitution Asp240-Gly (Ambler numbering) (1). (ii) The second interesting feature was the inverted repeat right (IRR) sequence of ISEcp1B 80 bp upstream of the ATG start codon of CTX-M-32. No putative promoter sequences were found in the 80-bp sequence that separated the IRR of ISEcp1B from the ATG site of the blaCTX-M-32 gene; moreover, this IRR provided –35 and –10 promoter sequences, thus probably contributing to the expression of the blaCTX-M-32 gene. (iii) Third, this IRR was downstream of a tnpA gene that encoded the transposase of IS5. Figure 1 shows the 2,326-bp sequence of the original 4-kpb KpnI fragment.





View larger version (108K):
[in this window]
[in a new window]
  		FIG. 1. Nucleotide sequence of a 2,326-bp DNA fragment of the pMC-2 plasmid. The deduced amino acid sequence is indicated in single-letter code below the nucleotide sequence. Stop codons are indicated by asterisks. The –35 and –10 promoter sequences of the blaCTX-M-32 gene and the IRR sequence of ISEcp1 are underlined and indicated by bold letters, as is the +1 position of the transcriptional start of the blaCTX-M-32 gene (10). The CTX-M-32 and transposase of IS5 proteins are indicated by arrows. Bold amino acids are those conserved in class A ß-lactamases (15). Oligonucleotides used for sequencing are indicated by arrows, and KpnI restriction sites delimiting the 4-kbp insert are also underlined.

To purify the CTX-M enzyme, the blaCTX-M-32 gene was cloned in the pGEX-6P-1 vector, which allowed a fusion protein between glutathione S-transferase (GST) and the CTX-M enzyme. The ß-lactamase was purified to homogeneity following the manufacturer's directions for the GST gene fusion system (Amersham Pharmacia Biotech, Europe GmbH). The purified protein appeared on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a band of 28 kDa (>=99% pure) (Fig. 2).



View larger version (63K):
[in this window]
[in a new window]
  		FIG. 2. Electrophoresis analysis of CTX-M-32 and CTX-M-1 purified extracts in a sodium dodecyl sulfate-10% polyacrylamide gel electrophoresis gel stained with Coomassie brilliant blue R-250. Lanes: 1, protein molecular markers; 2, purified CTX-M-1 protein used in kinetic experiments; 3, purified CTX-M-32 protein used in kinetic experiments.

For kinetic experiments, CTX-M-32 ß-lactamase was used at a 1,800 µM concentration. The ß-lactamase showed a hydrolytic profile similar to that expected for a molecular class A CTX-M enzyme (6), with the Km for ampicillin lower than the Km for cefalothin, a Km for cefotaxime of <500 µM, and a clear hydrolytic activity towards cefotaxime. Moreover, moderate hydrolytic activity was detected against ceftazidime, as ceftazidime MICs suggested (Table 2).


View this table:
[in this window]
[in a new window]
  		TABLE 2. Substrate profile of ß-lactamase CTX-M-32

The CTX-M-32 enzyme is derived from CTX-M-1 by a single amino acid replacement, Asp240-Gly. To confirm the importance of the Asp-Gly substitution in the hydrolysis of ceftazidime, we replaced the Gly240 with Asp in CTX-M-32 by using site-directed mutagenesis as previously described (14). The CTX-M-32mut or CTX-M-1 gene was then cloned into the pBGS18– vector, yielding the pMC-3 plasmid. The mutagenesis was confirmed by nucleotide sequencing. The MICs for E. coli TG1 harboring pMC-2 and pMC-3 are shown in Table 1. The MICs of ceftazidime corresponding to E. coli TG1 harboring CTX-M-1 ß-lactamase were clearly lower than those corresponding to E. coli TG1 carrying CTX-M-32. To confirm this result, the substrate profile of the CTX-M-1 ß-lactamase was determined with the enzyme purified as mentioned above for CTX-M-32 (GST gene fusion system) (Fig. 2). For kinetic experiments, CTX-M-1 ß-lactamase was used at a 1,670 µM concentration. Kcat/Km (in micromolar per second) values for ceftazidime and cefotaxime were 0.0001 and 1.5; therefore, a lower catalytic efficiency with respect to ceftazidime was detected with CTX-M-1, according to the differences in ceftazidime MICs between CTX-M-32 and CTX-M-1 enzymes (Table 1).

Three different enzymes, CTX-M-15, -16, -19 and, recently, CTX-M-27 have been reported to be associated with ceftazidime hydrolysis (4, 5, 20, 21). The amino acid changes associated with the phenotype of ceftazidime hydrolysis were a Pro-to-Ser substitution at position 167 in CTX-M-19 with respect to CTX-M-18 (20) and an Asp-to-Gly substitution at position 240 in CTX-M-16 with respect to CTX-M-9 (4) and in CTX-M-27 with respect to CTX-M-14 (5). In agreement with these previous results, we also report that the Asp240 substitution is a key factor in the evolution of CTX-M ß-lactamases, as it increases their hydrolytic activity toward ceftazidime.

Regarding the CTX-M enzymes, to our knowledge only six different enzymes have been published in the group 1 CTX-M enzymes: CTX-M-1, -3, -10, -12, -15, and -32 (3, 16, 19, 20). Among these, only CTX-M-15 and -32 showed more efficient ceftazidime hydrolysis than their parental enzymes, CTX-M-3 and CTX-M-1, respectively. The two former enzymes share the same amino acid substitution, although CTX-M-15 differs from CTX-M-32 in four additional amino acid changes. In terms of evolution, CTX-M-32 is probably an ancestor between CTX-M-1 and CTX-M-15 and constitutes a step forward in the evolution of ß-lactamase in broad-spectrum hydrolysis of antibiotics such as ceftazidime.

In summary, we report the genetic and biochemical characterization of a new CTX-M enzyme, CTX-M-32. This is the fourth report of a CTX-M ß-lactamase isolation in Spain, as CTX-M-9, CTX-M-10, and CTX-M-14 have previously been isolated in this country (7, 19, 22, 24).

Nucleotide sequence accession number. The GenBank accession number for the CTX-M-32 ß-lactamase is AJ557142.

..


arrow
ACKNOWLEDGMENTS
 
This work was supported by Direccion Xeral de I+D, Xunta de Galicia (PGIDT01PXR90101PR and PGIDIT02SAN91604PR) and Fondo de Investigaciones Sanitarias (PI021415).


arrow
FOOTNOTES
 
* Corresponding author. Mailing address: Servicio de Microbiologia, Complejo Hospitalario Universitario Juan Canalejo, C/Xubias de Arriba s/n, 15006 La Coruña, Spain. Phone: 981-178000, ext. 21144. Fax: 981-178216. E-mail: germanbou{at}canalejo.org. Back


arrow
REFERENCES
 
    1
  1. Ambler, R. P., A. F. W. Coulson, J. M. Frere, J. M. Ghuysen, B. Joris, M. Forsman, et al. 1991. A standard numbering scheme for the class A ß-lactamases. Biochem. J. 276:269-270.
    2. 2
  2. Barthélémy, M., J. Péduzzi, H. Bernard, C. Tancrède, and R. Labia. 1992. Close amino acid sequence relationship between the new plasmid-mediated extended-spectrum ß-lactamase MEN-1 and chromosomally encoded enzymes of Klebsiella oxytoca. Biochim. Biophys. Acta 1122:15-22.[CrossRef][Medline]
    3. 3
  3. Bauernfeind, A., I. Stemplinger, R. Jungwirth, S. Ernst, and J. M. Casellas. 1996. Sequences of beta-lactamase genes encoding CTX-M-1 (MEN-1) and CTX-M-2 and relationship of their amino acid sequences with those of other beta-lactamases. Antimicrob. Agents Chemother. 40:509-513.[Abstract]
    4. 4
  4. Bonnet, R., C. Dutour, J. L. Samapaio, C. Chanal, D. Sirot, R. Labia, C. D Champs, and J. Sirot. 2001. Novel cefotaximase (CTX-M-16) with increased catalytic efficiency due to substitution Asp-240-Gly. Antimicrob. Agents Chemother. 45:2269-2275.[Abstract/Free Full Text]
    5. 5
  5. Bonnet, R., C. Recule, R. Baraduc, C. Chanal, D. Sirot, C. De Champs, and J. Sirot. 2003. Effect of D240G substitution in a novel ESBL CTX-M-27. J. Antimicrob. Chemother. 52:29-35.[Abstract/Free Full Text]
    6. 6
  6. Bonnet, R., J. L. Sampaio, R. Labia, C. De Champs, D. Sirot, C. Chanal, and J. Sirot. 2000. A novel CTX-M ß-lactamase (CTX-M-8) in cefotaxime-resistant Enterobacteriaceae isolated in Brazil. Antimicrob. Agents Chemother. 44:1936-1942.[Abstract/Free Full Text]
    7. 7
  7. Bou, G., M. Cartelle, M. Tomas, D. Canle, F. Molina, R. Moure, J. M. Eiros, and A. Guerrero. 2002. Identification and broad dissemination of the CTX-M-14 beta-lactamase in different Escherichia coli strains in the northwest area of Spain. J. Clin. Microbiol. 40:4030-4036.[Abstract/Free Full Text]
    8. 8
  8. Bradford, P. A. 2001. Extended-spectrum ß-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistant threat. Clin. Microbiol. Rev. 14:933-951.[Abstract/Free Full Text]
    9. 9
  9. Bush, K., G. A. Jacoby, and A. A. Medeiros. 1995. A functional classification scheme for ß-lactamases and its correlation with molecular structure. Antimicrob. Agents Chemother. 39:1211-1233.[Medline]
    10. 10
  10. Cao, V., T. Lambert, and P. Courvalin. 2002. ColE1-like plasmid pIP843 of Klebsiella pneumoniae encoding extended-spectrum ß-lactamase CTX-M-17. Antimicrob. Agents Chemother. 46:1212-1217.[Abstract/Free Full Text]
    11. 11
  11. Chanawong, A., F. H. M'Zali, J. Heritage, J. H. Xiong, and P. M. Hawkey. 2002. Three cefotaximases, CTX-M-9, CTX-M-13, and CTX-M-14, among Enterobacteriaceae in the People's Republic of China. Antimicrob. Agents Chemother. 46:630-637.[Abstract/Free Full Text]
    12. 12
  12. Coque, T. M., A. Oliver, J. C. Pérez-Díaz, F. Baquero, and R. Cantón. 2002. Genes encoding TEM-4, SHV-2, and CTX-M-10 extended-spectrum ß-lactamases are carried by multiple Klebsiella pneumoniae clones in a single hospital (Madrid, 1989 to 2000). Antimicrob. Agents Chemother. 46:500-510.[Abstract/Free Full Text]
    13. 13
  13. Dutour, C., R. Bonnet, H. Marchandin, M. Boye, C. Chanal, D. Sirot, and J. Sirot. 2002. CTX-M-1, CTX-M-3, and CTX-M-14 ß-lactamases from Enterobacteriaceae isolated in France. Antimicrob. Agents Chemother. 46:534-537.[Abstract/Free Full Text]
    14. 14
  14. Ho, S. N., H. D. Hunt, R. M. Horton, J. K. Pullen, and L. R. Pease. 1989. Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene 77:51-59.[CrossRef][Medline]
    15. 15
  15. Joris, B., P. Ledent, O. Dideberg, E. Fonze, J. Lamotte-Brasseur, J. A. Kelly, J. M. Ghuysen, and J. M. Frere. 1991. Comparison of the sequences of class A ß-lactamases and of the secondary structure elements of penicillin-recognizing proteins. Antimicrob. Agents Chemother. 35:2294-2301.[Abstract/Free Full Text]
    16. 16
  16. Kariruki, S., J. E. Corkill, G. Revathi, R. Musoke, and C. A. Hart. 2001. Molecular characterization of a novel plasmid-encoded cefotaximase (CTX-M-12) found in clinical Klebsiella pneumoniae isolates from Kenya. Antimicrob. Agents Chemother. 45:2141-2143.[Abstract/Free Full Text]
    17. 17
  17. Matthew, M., A. M. Harris, M. J. Marshall, and G. W. Ross. 1975. The use of analytical isoelectric focusing for detection and identification of ß-lactamases. J. Gen. Microbiol. 88:169-178.[Medline]
    18. 18
  18. National Committee for Clinical Laboratory Standards. 2003. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M7-A6. National Committee for Clinical Laboratory Standards, Wayne, Pa.
    19. 19
  19. Oliver, A., J. C. Pérez-Díaz, T. M. Coque, F. Baquero, and R. Cantón. 2001. Nucleotide sequence and characterization of a novel cefotaxime-hydrolyzing ß-lactamase (CTX-M-10) isolated in Spain. Antimicrob. Agents Chemother. 45:616-620.[Abstract/Free Full Text]
    20. 20
  20. Poirel, L., M. Gniadkowski, and P. Nordmann. 2002. Biochemical analysis of the ceftazidime-hydrolysing extended-spectrum beta-lactamase CTX-M-15 and of its structurally related beta-lactamase CTX-M-3. J. Antimicrob. Chemother. 50:1031-1034.[Abstract/Free Full Text]
    21. 21
  21. Poirel, L., T. Naas, I. Le Thomas, A. Karim, E. Bingen, and P. Nordmann. 2001. CTX-M-type extended-spectrum beta-lactamase that hydrolyzes ceftazidime through a single amino acid substitution in the omega loop. Antimicrob. Agents Chemother. 45:3355-3361.[Abstract/Free Full Text]
    22. 22
  22. Sabate, M., R. Tarrago, F. Navarro, E. Miro, C. Verges, J. Barbe, and G. Prats. 2000. Cloning and sequence of the gene encoding a novel cefotaxime-hydrolyzing beta-lactamase (CTX-M-9) from Escherichia coli in Spain. Antimicrob. Agents Chemother. 44:1970-1973.[Abstract/Free Full Text]
    23. 23
  23. Sambrook, J., E. F. Fritsch, and T. Maniatis. 1989. Molecular cloning: a laboratory manual, 2nd ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
    24. 23
  24. Sanger, F., S. Nicklen, and A. R. Coulson. 1977. DNA sequencing with chain-terminating inhibitors. Proc. Natl. Acad. Sci. USA 74:5463-5467.[Abstract/Free Full Text]
    25. 24
  25. Simarro, E., F. Navarro, J. Ruiz, E. Miro, J. Gomez, and B. Mirelis. 2000. Salmonella enterica serovar Virchow with CTX-M-like beta-lactamase in Spain. J. Clin. Microbiol. 38:4676-4678.[Abstract/Free Full Text]
    26. 25
  26. Spratt, B., P. J. Hedge, T. S. Heesen, A. Edelman, and J. K. Broome-Smith. 1986. Kanamycin-resistant vectors that are analogues of plasmids pUC8, pUC9, pEMBL8, and pEMBL9. Gene 41:337-342.[CrossRef][Medline]

Antimicrobial Agents and Chemotherapy, June 2004, p. 2308-2313, Vol. 48, No. 6
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.6.2308-2313.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Szczepanowski, R., Linke, B., Krahn, I., Gartemann, K.-H., Gutzkow, T., Eichler, W., Puhler, A., Schluter, A. (2009). Detection of 140 clinically relevant antibiotic-resistance genes in the plasmid metagenome of wastewater treatment plant bacteria showing reduced susceptibility to selected antibiotics. Microbiology 155: 2306-2319 [Abstract] [Full Text]  
  • Celenza, G., Luzi, C., Aschi, M., Segatore, B., Setacci, D., Pellegrini, C., Forcella, C., Amicosante, G., Perilli, M. (2008). Natural D240G Toho-1 mutant conferring resistance to ceftazidime: biochemical characterization of CTX-M-43. J Antimicrob Chemother 62: 991-997 [Abstract] [Full Text]  
  • Lopez-Cerero, L., De Cueto, M., Saenz, C., Navarro, D., Velasco, C., Rodriguez-Bano, J., Pascual, A. (2008). Neonatal sepsis caused by a CTX-M-32-producing Escherichia coli isolate. J Med Microbiol 57: 1303-1305 [Abstract] [Full Text]  
  • Novais, A., Canton, R., Coque, T. M., Moya, A., Baquero, F., Galan, J. C. (2008). Mutational Events in Cefotaximase Extended-Spectrum {beta}-Lactamases of the CTX-M-1 Cluster Involved in Ceftazidime Resistance. Antimicrob. Agents Chemother. 52: 2377-2382 [Abstract] [Full Text]  
  • Vinue, L., Lantero, M., Saenz, Y., Somalo, S., de Diego, I., Perez, F., Ruiz-Larrea, F., Zarazaga, M., Torres, C. (2008). Characterization of extended-spectrum {beta}-lactamases and integrons in Escherichia coli isolates in a Spanish hospital. J Med Microbiol 57: 916-920 [Full Text]  
  • Perez-Llarena, F. J., Cartelle, M., Mallo, S., Beceiro, A., Perez, A., Villanueva, R., Romero, A., Bonnet, R., Bou, G. (2008). Structure-function studies of arginine at position 276 in CTX-M {beta}-lactamases. J Antimicrob Chemother 61: 792-797 [Abstract] [Full Text]  
  • Stepanova, M. N., Pimkin, M., Nikulin, A. A., Kozyreva, V. K., Agapova, E. D., Edelstein, M. V. (2008). Convergent In Vivo and In Vitro Selection of Ceftazidime Resistance Mutations at Position 167 of CTX-M-3 {beta}-Lactamase in Hypermutable Escherichia coli Strains. Antimicrob. Agents Chemother. 52: 1297-1301 [Abstract] [Full Text]  
  • Mendonca, N., Leitao, J., Manageiro, V., Ferreira, E., the Antimicrobial Resistance Surveillance Program, , Canica, M. (2007). Spread of Extended-Spectrum {beta}-Lactamase CTX-M-Producing Escherichia coli Clinical Isolates in Community and Nosocomial Environments in Portugal. Antimicrob. Agents Chemother. 51: 1946-1955 [Abstract] [Full Text]  
  • Fernandez, A., Gil, E., Cartelle, M., Perez, A., Beceiro, A., Mallo, S., Tomas, M. M., Perez-Llarena, F. J., Villanueva, R., Bou, G. (2007). Interspecies spread of CTX-M-32 extended-spectrum {beta}-lactamase and the role of the insertion sequence IS1 in down-regulating blaCTX-M gene expression. J Antimicrob Chemother 59: 841-847 [Abstract] [Full Text]  
  • Novais, A., Canton, R., Moreira, R., Peixe, L., Baquero, F., Coque, T. M. (2007). Emergence and Dissemination of Enterobacteriaceae Isolates Producing CTX-M-1-Like Enzymes in Spain Are Associated with IncFII (CTX-M-15) and Broad-Host-Range (CTX-M-1, -3, and -32) Plasmids. Antimicrob. Agents Chemother. 51: 796-799 [Abstract] [Full Text]  
  • Livermore, D. M., Canton, R., Gniadkowski, M., Nordmann, P., Rossolini, G. M., Arlet, G., Ayala, J., Coque, T. M., Kern-Zdanowicz, I., Luzzaro, F., Poirel, L., Woodford, N. (2007). CTX-M: changing the face of ESBLs in Europe. J Antimicrob Chemother 59: 165-174 [Abstract] [Full Text]  
  • Mugnaioli, C., Luzzaro, F., De Luca, F., Brigante, G., Perilli, M., Amicosante, G., Stefani, S., Toniolo, A., Rossolini, G. M. (2006). CTX-M-Type Extended-Spectrum {beta}-Lactamases in Italy: Molecular Epidemiology of an Emerging Countrywide Problem.. Antimicrob. Agents Chemother. 50: 2700-2706 [Abstract] [Full Text]  
  • Oteo, J., Navarro, C., Cercenado, E., Delgado-Iribarren, A., Wilhelmi, I., Orden, B., Garcia, C., Miguelanez, S., Perez-Vazquez, M., Garcia-Cobos, S., Aracil, B., Bautista, V., Campos, J. (2006). Spread of Escherichia coli Strains with High-Level Cefotaxime and Ceftazidime Resistance between the Community, Long-Term Care Facilities, and Hospital Institutions.. J. Clin. Microbiol. 44: 2359-2366 [Abstract] [Full Text]  
  • Valenzuela de Silva, E. M., Mantilla Anaya, J. R., Reguero Reza, M. T., Gonzalez Mejia, E. B., Pulido Manrique, I. Y., Dario Llerena, I., Velandia, D. (2006). Detection of CTX-M-1, CTX-M-15, and CTX-M-2 in Clinical Isolates of Enterobacteriaceae in Bogota, Colombia.. J. Clin. Microbiol. 44: 1919-1920 [Full Text]  
  • Delmas, J., Robin, F., Carvalho, F., Mongaret, C., Bonnet, R. (2006). Prediction of the Evolution of Ceftazidime Resistance in Extended-Spectrum {beta}-Lactamase CTX-M-9. Antimicrob. Agents Chemother. 50: 731-738 [Abstract] [Full Text]  
  • Brinas, L., Lantero, M., de Diego, I., Alvarez, M., Zarazaga, M., Torres, C. (2005). Mechanisms of resistance to expanded-spectrum cephalosporins in Escherichia coli isolates recovered in a Spanish hospital. J Antimicrob Chemother 56: 1107-1110 [Abstract] [Full Text]  
  • Di Conza, J. A., Gutkind, G. O., Mollerach, M. E., Ayala, J. A. (2005). Transcriptional Analysis of the blaCTX-M-2 Gene in Salmonella enterica Serovar Infantis. Antimicrob. Agents Chemother. 49: 3014-3017 [Abstract] [Full Text]  
  • Politi, L., Tassios, P. T., Lambiri, M., Kansouzidou, A., Pasiotou, M., Vatopoulos, A. C., Mellou, K., Legakis, N. J., Tzouvelekis, L. S. (2005). Repeated Occurrence of Diverse Extended-Spectrum {beta}-Lactamases in Minor Serotypes of Food-Borne Salmonella enterica subsp. enterica. J. Clin. Microbiol. 43: 3453-3456 [Abstract] [Full Text]  
  • Brinas, L., Moreno, M. A., Teshager, T., Saenz, Y., Porrero, M. C., Dominguez, L., Torres, C. (2005). Monitoring and Characterization of Extended-Spectrum {beta}-Lactamases in Escherichia coli Strains from Healthy and Sick Animals in Spain in 2003. Antimicrob. Agents Chemother. 49: 1262-1264 [Abstract] [Full Text]  
  • Woodford, N., Ward, M. E., Kaufmann, M. E., Turton, J., Fagan, E. J., James, D., Johnson, A. P., Pike, R., Warner, M., Cheasty, T., Pearson, A., Harry, S., Leach, J. B., Loughrey, A., Lowes, J. A., Warren, R. E., Livermore, D. M. (2004). Community and hospital spread of Escherichia coli producing CTX-M extended-spectrum {beta}-lactamases in the UK. J Antimicrob Chemother 54: 735-743 [Abstract] [Full Text]  

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cartelle, M.
Right arrow Articles by Bou, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cartelle, M.
Right arrow Articles by Bou, G.

Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»