Integrons are regions of DNA that gather together other DNA regions having the potential to encode proteins. Integrons then convert those regions into functional genes by placing them next to an active promoter, a region of DNA where RNA polymerase binds and begins making mRNA from an adjacent gene. Integrons do not move themselves, but instead they bring relatively small gene cassettes into an insertion site located next to a gene encoding a recombinase (integrase). To be moved into an integron, a region of DNA needs to have only a sequence that is related to the nucleotide sequence at the insertion site. Many of the "procured" genes encode proteins responsible for antibiotic resistance. Consequently, integrons, by accumulating sets of resistance genes, confer multidrug resistance (see Box 6-4). Integrons are involved in resistance to aminoglycosides, chloram-phenicol, trimethoprim, rifampicin, erythromycin, fosfomycin, lincomycin, antiseptics of the quaternary ammonium family, and all known p-lactams.149
Integrons can move when they are located inside a transposon. Mobile integrons are found in many clinical isolates of multidrug-resistant bacteria and are a special problem with urinary infections. An example was reported from Uruguay in which 104 patient samples were examined.150 Forty-six isolates were multidrug resistant, and 33 contained integrons (most of the integron-containing isolates were also multidrug resistant); one of the Klebsiella pneumoniae isolates contained 2 integrons and was resistant to 8 antibiotics. Nucleotide sequence analysis of some of the integrons revealed a complex history involving insertion into a transposon and homologous recombination between transposons. This type of study emphasizes how dynamic microbial DNA can be, moving pieces from one organism to another, inserting DNA pieces into other DNA molecules, and forming new combinations through genetic recombination.
Integrons are found in both Gram-positive and Gram-negative bacteria, suggesting that they may have an ancient origin. Nucleotide sequence analysis also reveals that they have combined genes from many different bacteria. One line of evidence derives from codon usage. During protein synthesis, amino acids are joined to tRNA molecules, one amino acid per tRNA. Most amino acids can bind to several tRNA types (one amino acid per tRNA molecule). Each type of tRNA has a different anticodon; consequently, each type recognizes a different codon in mRNA. For a particular amino acid, a given bacterial species tends to use one type of tRNA more often than the others. Therefore, mRNA shows a bias for certain codons, a bias characteristic of the bacterial species. That bias is called codon usage. Analysis of codon usage for genes assembled by integrons reveals a wide diversity, indicating diverse origins for present-day integrons.
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