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Antimicrobial Agents and Chemotherapy, July 2007, p. 2658-2659, Vol. 51, No. 7
0066-4804/07/$08.00+0     doi:10.1128/AAC.00364-07

LETTERS TO THE EDITOR

Genetic Environment of ISEcp1 and bla_ACC-1

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A recent paper (8) presented analyses of the genetic environments of the bla_ACC-1 β-lactamase gene, which originates from the Hafnia alvei chromosome (7), associated with truncated ISEcp1 elements in Enterobacteriaceae. In three Klebsiella pneumoniae isolates (SKL54 [GenBank accession no. AJ870922], SKL55, and C5900 [AJ870923]) ISEcp1 was described as having a 1,433-bp deletion due to insertion of IS26 (IS26_R; Fig. 1A). A second copy of IS26 (IS26_L) in the opposite orientation was found adjacent to a second truncated ISEcp1 (ISEcp1_L) with the 3' deletion "exactly complementary to that of ISEcp1 upstream from bla_ACC-1." The authors suggested that a composite transposon with directly oriented flanking IS26 elements was inserted into ISEcp1, with subsequent unexplained events giving the observed configuration.

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FIG. 1. (A) Schematic representation of part of AJ870922. (B) Inversion of the region between IS26L and IS26R restores matching DR. (C) Removal of IS26L plus one DR regenerates a complete ISEcp1. (D) Other sequences with elements in common with AY870922/AY80923. For panels A to D, IS26 elements are shown as wide boxes, with the pointed ends indicating their orientation and selected adjacent 8-bp sequences shown above their ends. ISEcp1 elements are narrower boxes with an arrow indicating the position of the transposase gene. The extents and positions of other genes are shown as open arrows labeled with the gene name. (E) Alignment of sequences defining the ISEcp1-blaACC-1 transposon. GenBank accession numbers from which the sequences were obtained are given on the left. The start codon of the gdhA gene (encoding a glutamate dehydrogenase) is labeled and in lowercase. The 14-bp region that may correspond to the IR used by ISEcp1 when transposing blaACC-1 is boxed, and bases matching the IR of ISEcp1 are in boldface. Sequences potentially corresponding to DR are underlined.

An alternative explanation for this configuration is suggested by the sequences adjacent to the ends of IS26, which produces 8-bp direct repeats (DR) of target DNA on transposition (2). In AJ870922 and AJ870923, 8-bp sequences that are the reverse complements of one another are found adjacent to one end of IS26_L (AAAATGTC) and one end of IS26_R (GACATTTT) (Fig. 1A), suggesting that the region between these two IS26 elements could have been inverted by homologous recombination between them. Reversing this event would give the configuration shown in Fig. 1B, with matching DR flanking IS26_L. Removal of IS26_L plus one copy of this 8-bp DR sequence would regenerate a complete ISEcp1 (Fig. 1C).

ISEcp1B (which differs from ISEcp1 by three nucleotides [10]) has been shown to mobilize an adjacent bla_CTX-M-19 gene (10) and to transfer the bla_CTX-M-2 gene from the Kluyvera ascorbata chromosome to plasmids (6). It appears that sequences other than the right inverted repeat (IR_R) of ISEcp1, but which have some bases in common with this 14-bp IR, are used during the transposition process (6, 10). A presumed transposon consisting of ISEcp1, bla_CTX-M, and the region up to and including the alternative IR is flanked by 5-bp DR (6, 10). A structure including ISEcp1-bla_CTX-M-15 and flanked by 5-bp DR is also found in the plasmid pC15-1a (1).

As mentioned by Doloy et al. (3), ISEcp1 may have been similarly responsible for mobilizing the bla_ACC-1 gene and adjacent DNA from H. alvei. GenBank entries of bla_ACC-1 from H. alvei (e.g., AF180952 [4]) include insufficient flanking sequence to define the region that has been transferred. However, a plasmid from Salmonella enterica serovar Bareilly (AY856832 [5]) also contains part of ISEcp1and bla_ACC-1 (Fig. 1D), and alignment of the sequence beyond the 3' end of bla_ACC-1 with the equivalent region from AY870922/AY870923 suggested a potential IR sequence (Fig. 1E).

A search (http://www.ncbi.nlm.nih.gov/BLAST) with the sequence from AY870922/AY870923 beyond this putative IR identified GenBank accession no. EF104648 (8), which includes a gene encoding a putative glycosidase, orf1 from the work of Doloy et al. (3), reidentified as a novel β-lactamase gene, bla_SCO-1, and IS26 (Fig. 1D). Part of the glycosidase gene and bla_SCO-1, but not IS26, are also found in EF063111 (9). A search with the corresponding sequence from AY856832 identified AJ519722 (11). An alignment of the four different sequences (Fig. 1E) seemed to confirm the proposed IR and suggested that the same region of the H. alvei chromosome has been transferred to both K. pneumoniae and S. enterica serovar Bareilly plasmids. The origin of one T residue is ambiguous, but excluding this T from the IR gives 6/14 matches with the ISEcp1 IR (Fig. 1E). The sequences thus predicted as DR for AY870922/AY870923 and AY856832 (TTGAA and TAATA, respectively; Fig. 1E) are AT rich, as previously noted (6, 10), but these cannot be confirmed in the absence of sequence adjacent to IR_L of ISEcp1.

Thus, bla_ACC-1 may have been picked up from the H. alvei chromosome by ISEcp1 and inserted into different locations, including adjacent to bla_SCO-1 and IS26. Subsequent events, such as the insertion of IS26 into ISEcp1 and IS26-mediated inversion described for SLK54 and SLK55/C5900, may also explain the other configurations seen by Doloy et al. (3).

 
S.R.P. is partly supported by a Centre of Clinical Research Excellence grant from the National Health and Medical Research Council of Australia (no. 264625).

I thank Laurent Poirel for kindly providing GenBank accession no. EF063111 prior to its release.

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8. Papagiannitsis, C. C., A. Loli, L. S. Tzouvelekis, E. Tzelepi, G. Arlet, and V. Miriagou. 2007. SCO-1, a novel plasmid-mediated class A β-lactamase with carbenicillinase characteristics from Escherichia coli. Antimicrob. Agents Chemother. 51:2185-2188.[Abstract/Free Full Text]
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						Sally R. Partridge Centre for Infectious Diseases and Microbiology University of Sydney Westmead Hospital Westmead, NSW 2145, Australia
						Phone: (61-2) 9845 6278, Fax: (61-2) 9891 5317, E-mail: sallyp{at}icpmr.wsahs.nsw.gov.au

Author's Reply

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The analysis of the genetic environment of ACC-1 is very well described and interesting. This analysis confirms strongly the first event, the mobilization of the genes bla_ACC-1 and gdhA by the insertion sequence ISEcp1.

						Guillaume Arlet Hôpital Tenon, UFR Saint-Antoine Bacteriology 4, rue de la Chine Paris 75970 cedex 20, France
						Phone: 33 1 56 01 70 18, Fax: 33 1 56 01 61 08, E-mail: guillaume.arlet{at}tnn.ap-hop-paris.fr

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Antimicrobial Agents and Chemotherapy, July 2007, p. 2658-2659, Vol. 51, No. 7
0066-4804/07/$08.00+0     doi:10.1128/AAC.00364-07

This article has been cited by other articles:

• Jacoby, G. A. (2009). AmpC {beta}-Lactamases. Clin. Microbiol. Rev. 22: 161-182 [Abstract] [Full Text]  

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