The extended-spectrum β-lactamase (ESBL) GES-1 was initially described from a Klebsiella pneumoniae strain in 1998 (5). Since then, two closely related enzymes, IBC-1 and GES-2, have also been described (4, 6). A GES-1-producing K. pneumoniae strain has been reported from a French hospital, although the patient had just been transferred from French Guiana, South America. blaGES-1 has also been found in a Pseudomonas aeruginosa strain isolated in another French medical center (3) and in K. pneumoniae in Lisbon, Portugal (2).
The GES-1-producing P. aeruginosa, isolate 48-8896, was recovered from a 63-year-old female who had a hysterectomy (São Paulo, Brazil) and developed a wound infection while receiving ceftriaxone, amikacin, and metronidazole. Blood cultures were drawn and were positive for P. aeruginosa. Polymyxin B plus vancomycin was started empirically and the infection was eradicated, but the patient died after being hospitalized in the intensive care unit for 3 months. Isolate 48-8896 showed resistance to imipenem MIC, >8 μg/ml), meropenem (MIC, >8 μg/ml), ceftazidime (MIC, >16 μg/ml), cefepime (MIC, >16 μg/ml), piperacillin-tazobactam (MIC, >64 μg/ml), and all antimicrobial agents evaluated (including aminoglycosides and quinolones), except for polymyxin B (MIC, ≤1 μg/ml). Phenotypic detection of ESBL was determined to be positive using the (ceftazidime/ceftazidime-clavulanic acid and cefepime/cefepime-clavulanic acid) Etest strips (AB BIODISK, Solna, Sweden).
Since several β-lactamase genes are part of gene cassettes that are class 1 integron mediated and most of them contain an aminoglycoside acetyltransferase gene cassette, primers located in the 5′ conserved segment region (5′-CS) (5′-CCAAGCTCTCGGGTAACATC-3′) and in the flanking region of the aacA4 gene cassette (5′-AACTTGCGAGCGATCCGATG-3′) were used. PCR amplification and subsequent sequencing analyses of the 1,211-bp PCR product showed a blaGES-1 in the first position of a class 1 integron (Fig. 1).
The integron harboring blaGES-1 showed a similar adjacent and upstream context as described in the first report of GES-1 (K. pneumoniae ORI-1) (5). Beyond blaGES-1 was intI1, encoding the integrase of a class 1 integron. Between blaGES-1 and intI1 was an attI1 site and two promoters (P2 and Pant). However, the P2 promoter appears to have an absence of three G residues, and the space between the −35 and −10 sequences is 14 bp (Fig. 1). The secondary promoter (P2) is created by the insertion of the three Gs, increasing the space between the −35 and −10 regions to 17 bp (1). This evidence suggests that P2 was probably not contributing to the transcription of blaGES-1, as previously described in other integrons harboring this ESBL gene (3, 5). As determined in this study, beyond the blaGES-1 integron lies a chloramphenicol-acetyltransferase gene cassette, catB8, followed by the 3′-CS region of the class 1 integron, which is unique among blaGES-1 genes.
The detection of a GES-1-producing P. aeruginosa isolate in Latin America (Brazil) was a very worrisome finding, since it heralds the possibility for the emergence and future dissemination of new GES derivatives with broader spectrums of hydrolyses, such as the carbapenem-hydrolyzing enzyme GES-2 (6).
Schematic representations of different blaGES-1-containing integrons (a, b, c). The location of the three G residues found in the P2 of P. aeruginosa 48-8896 is highlighted. The 59 bp are represented with black dots.
ACKNOWLEDGMENTS
The SENTRY program was funded by an educational research grant from Bristol-Myers Squibb.
- American Society for Microbiology
