## 1 Introduction  
_Integron Functionality Is Directly Linked with Adaptation on Demand_  
Integons are versatile genetic platforms involved with the acquisition, stockpiling, excision, and rearrangements of gene cassettes by site-specific recombination events mediated by integrase activity [1]. Cassettes are circular mobilizable structures comprising a gene bounded to a cassette-associated recombination site, called _attC_. In general, genes included in cassettes are devoid of promoter sequences due to the proximity of their initiation codons and the 5' boundary of the cassette [2]. The basic structure of an integration comprises the _intI_ integrase gene, a member of the tyrosine recombinase family, the _attI_ recombination site, where cassettes are recombined, the P\({}_{\text{intI}}\) integrase promoter, and a common promoter (Pc), generally embedded in _intI_, that drives the expression of promoterless cassette-associated genes, featuring the integrons as natural expression vectors [2, 3] (Figure 1). The integration of a circular cassette intermediate preferentially occurs at the _attI_ site (_attI_ X _attC_), ensuring the immediate expression of the new integrated cassettes by the upstream Pc promoter. During cassette excision, the integrase catalyzes recombination between two adjacent _attC_ sites (_attC_ X _attC_) [4]. These site-specific reactions mediated by the integrase precisely occur between the first and second bases of the 7-bp core site sequence GTTRRY shared among _attI_ and _attC_ sites (Figure 1) [5, 6]. Several classes of integrons have been recognized based on integrase protein sequences, which shared 45-59% amino acid identity. Three major integron classes (classes 1, 2, and 3) are featured by their strong link with antibiotic resistance gene cassettes and the emergence of resistance phenotypes and, therefore, these elements have been considered resistance integrons (RIs). Moreover, due to their intimate association with mobile genetic elements, these integrons classes were also classified as mobile integrons (MIs), constituting the major vectors of antibiotic resistance spread among bacteria. The class 1 and 3 integrons are associated with Tn402-related transposons, while class 2 integrons are only found in association with the Tn7 transposon module [7]. In spite of these common features, the RIs/MIs present some peculiarities. Among them, class 1 integrons are the most widespread and have been continuously involved with resistance emergence to a remarkable range of antibiotic treatments. Together with its 5\({}^{\prime}\) conserved segment (CS), composed by the _intI1_ integrase gene, the _attI1_ recombination site, and the Pc and P\({}_{\text{intI1}}\) promoters [2; 3], the class 1 integrins also present a 3\({}^{\prime}\)CS. This region comprises the gene cassettes _qacE\(\Delta\)1_, fused in its 3\({}^{\prime}\) end with the _suI1_, which confer resistance to quaternary ammonium compounds and sulfonamides, respectively, followed by _ovf5_ of unknown function [1]. This class is also characterized by harboring a huge variety of resistance gene cassettes involved with resistance to non-related antibiotic classes, such as aminoglycos, \(\beta\)-lactams, carbapenem, trimethoprim, chloramphenicol, rifamp, fluoroquinolones, macrolides, and streptomycin [1; 5; 7]. On the other hand, although  
Figure 1: Schematic representation of integron structure and functionality. The integrase _intI_, the _attI_ recombination site, and the P\({}_{\text{intI}}\) and Pc promoters are showed. The gene cassettes and their cognate _attC_ recombination sites are indicated by circles and arrows representing the free circular and integrated forms, respectively. The site-specific recombination events (integration and excision) mediated by IntI integrase are indicated. Cassette transcripts generated from the Pc promoter are indicated by curved lines.