This paper examines integrons — bacterial genetic systems that capture and express foreign DNA — and their central role in the rapid emergence of antibiotic resistance. Drawing primarily on Rowe-Magnus et al.'s 2001 PNAS study, the paper describes how integrons function as natural cloning systems, how multiresistant integrons (MRIs) accumulate multiple resistance gene cassettes, and how super-integrons (SIs) distributed across gamma-proteobacteria likely served as evolutionary ancestors to MRIs. The paper also discusses the proposed relationship between bacteriophages and the ancestral integron platform, and considers the broader significance of integrons for bacterial genome evolution over hundreds of millions of years.
Research into integrons has been driven by the alarmingly rapid appearance of antibiotic resistance among a number of bacteria linked to widespread disease in the last century. These bacteria have become an increasing threat to human health and have often been featured in the media as "superbugs" that may evade any attempts to control their effects using antibiotic treatments. As a result, research into the genetic mechanisms that bacteria use to acquire genetic resistance has been followed with growing interest. The discovery of integrons may well therefore become known as one of the most important stepping-stones in this research (Rowe-Magnus).
Integrons are bacterial systems that allow bacteria to capture and express DNA from other bacteria. Integrons capture foreign gene cassettes that code for important metabolic functions. Many of these gene cassettes contain genetic material that confers resistance to antibiotic drugs. There are over 70 different antibiotic resistance genes known in gene cassettes, a number that coincides with most of the antimicrobial drugs in use today (Rowe-Magnus).
Integrons are "natural cloning and expression systems that incorporate open reading frames and convert them to functional genes" (Rowe-Magnus et al., 652). An integrase is coded for by the integron platform, and the integrase then acts to mediate the recombination that occurs between a secondary target (attC site) and a primary recombination site (attI) (Rowe-Magnus et al.).
The presence of antimicrobial resistance cassettes in integrons presents an enormous challenge to maintaining the effectiveness of antibacterial drugs. Clinically isolated bacteria that have resistance to multiple drugs have been shown to carry integrons with up to eight resistance cassettes (Rowe-Magnus).
Multiresistant integrons (MRIs) have an extensive system of multiple combinations of antibiotic resistance gene cassettes. These elements are crucial to the rapid appearance of antibiotic resistance among a wide number of Gram-negative bacteria (Rowe-Magnus et al., 2001). Integrons have also likely played an important and crucial role in the broader evolution of the bacterial kingdom, acting even beyond the recent acquisition of antibacterial resistance. A given bacterial genome can contain up to one fifth of its total genome as foreign DNA (Rowe-Magnus et al.).
Despite their clear importance to the rapid appearance of antibiotic resistant bacteria, little was fully understood about the evolutionary history of MRIs (Rowe-Magnus). In a 2001 PNAS paper entitled "The evolutionary history of chromosomal super-integrons provides an ancestry for multiresistant integrons," Rowe-Magnus et al. investigated this evolutionary history in detail.
The authors based their work on the recent discovery of a chromosomal integron in the Vibrio cholerae genome that was demonstrated to harbor hundreds of cassettes. They argue that super-integrons (SIs) evolved into MRIs through the entrapment of intI genes and attI sites into structures resembling transposons. Based on this assumption, the authors predicted that SI integrases should be active and numerous in the bacterial kingdom, and that cassettes should encode adaptive functions.
Ultimately, the authors demonstrated that equivalent integron structures exist throughout the gamma-proteobacterial radiation. They further noted that the integrase of Vibrio cholerae is identical to the MRI class 1 integrase. In addition, the metabolic activity of three SI cassettes was identified.
SI structures were identified in V. mimicus, V. metschnikovii, V. parahaemolyticus, L. pelagia, and V. fischeri. Each of the Vibrio SIs was found to contain a 100 kB SI. Many gamma-proteobacteria genera were also found to have SIs, including Shewanella and Xanthomonas. Pseudomonas alcaligenes and Pseudomonas mendocina have also had SIs recently characterized (Rowe-Magnus et al.).
"Proposed prophage origin of the integron platform"
"Integrons' broader role in bacterial evolution"
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