Integrons in the development of antimicrobial resistance: critical review and perspectives

Basharat Ahmad Bhat¹Dr. Rakeeb Ahmad Mir²Hafsa Qadri¹Rohan Dhiman³Mustfa F Alkhanani⁴Abdullah Almilaibary⁵Manzoor A Mir^1*

• ¹University of Kashmir, Srinagar, India
• ²Central University of Kashmir, Ganderbal, India
• ³National Institute of Technology Rourkela, Rourkela, India
• ⁴University of Hafr Al Batin, Hafar Al Batin, Saudi Arabia
• ⁵Albaha University, Al Aqiq, Saudi Arabia

In the published article, there was an error. Some portions of the manuscript were inadvertently published without appropriate citation. We acknowledge this unintentional oversight and sincerely apologize for the mistake. The affected content has been corrected to ensure proper attribution, originality, and academic integrity. This correction does not alter the scientific conclusions presented in the article. Corrected Text and Clarifications A correction has been made to the sections: "Integron Definition," "attC Sites," and "Gene Cassettes" on pages 3–4. Original Text (Published Version) [The text you provided from the originally published article would be referenced or attached in the corrigendum, but for brevity, we omit repeating it here.] Corrected Version Integron Definition An integron is typically characterized by the presence of an integrase gene (intI) located near a primary recombination site known as attI (Deng et al., 2015). Figure 1: A schematic diagram of a class 1 integron displays its essential components: the P1 promoter, which drives gene cassette transcription; the P2 promoter, typically inactive; the int gene encoding the integrase enzyme; the attI1 integration site; the qacEΔ1 gene conferring resistance to quaternary ammonium compounds; the sul1 gene for sulfonamide resistance; an orf5 of unknown function; and associated P promoters regulating expression of resistance genes. The attC site on gene cassettes is specifically recognized by the integrase for recombination (Deng et al., 2015). attC Sites The attC region consists of two symmetrical sites, each comprising conserved short core sequences (7–8 base pairs) designated as R′ and R″, and L′ and L″. The R′ and R″ sequences align with the RH consensus, while L′ and L″ correspond to the LH consensus. These sequences are believed to guide the integrase in recognizing orientation-specific integration. The L″ site is especially important for determining insertion direction, and the LH site enhances the recombination efficiency of the RH site. Typically, an attC site is linked to a single open reading frame (ORF), forming a gene cassette. These cassettes, although sometimes independent, become a functional part of the integron upon integration (Deng et al., 2015). Basharat et al. Gene cassettes Studies have shown that the variable region of integrons may occasionally lack gene cassettes. When present, cassettes are integrated into the integron structure via site-specific recombination between attI and attC sites. These gene cassettes may exist as unstable circular DNA elements or as linear forms following directional insertion. Although they possess coding sequences, gene cassettes typically lack promoters and rely on the integrons promoter for expression. More than 130 distinct antibiotic resistance genes have been identified within these cassettes, conferring resistance to a broad range of antimicrobial agents, including β-lactams, aminoglycosides, chloramphenicol, streptothricin, trimethoprim, rifampin, erythromycin, quinolones, fosfomycin, lincomycin, and quaternary ammonium compounds. Antimicrobial resistance arises through both rare spontaneous mutations and, more significantly, acquisition of resistance genes via vertical and horizontal gene transfer. The latter is often mediated by mobile genetic elements such as plasmids and transposons. Integrons, frequently located on these elements, facilitate rapid bacterial adaptation and are implicated in the rise of multidrug-resistant organisms, often referred to as "superbugs" (Deng et al., 2015). Conclusion