During the past 20 years a significant amount of information related to the mechanism and spread of antibiotic resistance has become available. Recently, the impact of horizontally transmitted genetic determinants
and the role of recombination in the recruitment of resistance genes have been highlighted. Resistance genes can be exchanged among bacterial populations. Several mechanisms for the acquisition and dissemination of resistance determinants involve DNA exchange and in this way resistance genes can spread efficiently among bacterial populations from animals and humans . The identification of specialised genetic structures responsible for the acquisition of resistance genes on horizontal gene vehicles represents an important discovery in our understanding of antibiotic resistance mechanisms. Naturally occurring gene expression elements, called integrons, have been described as a very efficient genetic mechanism by which bacteria can acquire resistance genes. Integrons promote the capture of one or more gene cassettes within the same attachment site, thereby forming composite clusters of antibiotic resistance genes.
Integrons are gene expression systems that incorporate ORFs (open reading frames) and convert them into functional genes. The essential components of an integron include the integrase gene (intI), the attachment site (attI) and the promoter, which promotes the expression of any suitably integrated gene(s).
The most common integrons are classified by classes 1-3:
Class 1 represents the most common structure and most of the elements belonging to this class are characterized by the presence of two conserved segments, the 5’-conserved segment (5’-CS) and 3’-conserved segment (3’-CS). The 5’-CS contains the intI gene, the attI site and the promoter, while the 3’-CS codes for the sul1 gene, conferring resistance to sulphonamides and the qacED1 gene, conferring resistance to quaternary ammonium compounds used
as disinfectants. In addition, the 3’-CS carries the ORF5 encoding a protein of unknown function.
Class 2 integrons have also been described and these are included in the Tn7 family of transposons. Tn7 contains three integrated gene cassettes (dhfrIsat- aadA1) adjacent to a defective integrase gene (intI2) located at 5’-CS. The Tn7 attI site is located between the intI2 gene and the first inserted resistance gene as described for class 1 integrons. Class 2 integrons do not contain the sul1 gene but in fact include genes whose function promotes Tn7 transposition.
To date, only one class 3 integron has been reported, containing the blaIMP gene cassette that confers resistance to broadspectrum b-lactams including carbapenems, and part of the aacA4 gene, previously identified
as a gene cassette in class 1 integrons. The integrase gene (intI3) demonstrated an identity of 60.9% to the intI1 gene at the amino acid level, with the gene cassette boundaries showing atypical recombination sites. It is noteworthy that despite the differences in the integrase and attI site sequences, the same gene cassettes are thought to be acquired by all three integron classes, as identical gene cassettes have been found in classes 1 and 2 and in classes 1 and 3. This observation suggests that the class-specific integrases work on an apparently common pool of resistance gene cassettes.
Summary of the review:
Carattoli A. Importance of integrons in the diffusion of resistance. Vet Res. 2001 May-Aug;32(3-4):243-59. Review.
PMID: 11432416 [PubMed - indexed for MEDLINE]
