What are the Side Effects of Integron?

Keywords

Bacterial genomes, antibiotic-resistant pathogens, genome evolution, integrons, Gram-negative pathogens, antibiotic resistance.

Introduction

Integrons are genetic elements that allow efficient capture and expression of exogenous genes. They are widely known for their role in the dissemination of antibiotic resistance, particularly among Gram-negative bacterial pathogens. Exploration of integron diversity in natural environments has shown that they are more than just a curious feature of antibiotic-resistant pathogens but have a more general and important role in bacterial adaptation and genome evolution.

Integrons are versatile gene acquisition systems commonly found in bacterial genomes. They are ancient elements that are a hot spot for genomic complexity, generating phenotypic diversity and shaping adaptive responses. In recent times, they have had a major role in the acquisition, expression, and dissemination of antibiotic resistance genes. Assessing the ongoing threats posed by integrons requires an understanding of their origins and evolutionary history.

It shows how antibiotic use selected integrons from among the environmental pool of these elements, such that integrons carrying resistance genes are now present in most Gram-negative pathogens. The potential consequences of widespread pollution with the novel integrons that have been assembled via the agency of human antibiotic use and speculates on the potential uses of integrons as platforms for biotechnology.

Side Effects of Integrons in the Future

The widespread use of antibiotics has imposed strong selection for the assembly of mosaic DNA elements carrying multiple resistance genes. Integrons, their antibiotic resistance genes, and the mobile DNA elements they reside upon have become widely distributed, highly diverse, and abundant in human-dominated ecosystems.

They have the power to promote adaptation to changing environmental conditions by rapidly generating genetic variation. This allows integron-containing cells to overcome human strategies for controlling bacterial growth, but it also offers rich opportunities for gene prospecting and construction of new biosynthetic pathways.

Integrons and Resistance Genes as Pollutants

Antibiotic resistance genes and integrons are now viewed as significant environmental contaminants and as markers for tracing sources of pollution. The resistance genes and integrons emanating from human-dominated ecosystems can be regarded as xenogenetic pollutants, because these DNA elements have been assembled under the continuous selection exerted by human antibiotic use.

Unlike conventional pollutants, integrons and resistance genes can replicate and therefore have properties of both pollutants and invasive species. The human health implications of pollution with resistance genes have been the subject of considerable scrutiny, but less attention has been paid to their potential effects on natural environments.

Pollution with Selective Agents

When humans or animals are given antibiotic therapy, between 30 and 90% of the ingested compound is excreted to pollute wastewater. Antibiotics are also released in large quantities from pharmaceutical plants and are spread during manuring. Like resistance genes, antibiotics are difficult to remove during water treatment, and some have long half-lives in the environment, resulting in pollution of both rivers and the ocean.

The use of antibiotics in aquaculture adds these compounds directly into water bodies, raising local antibiotic concentrations. The environmental and health consequences of contaminating water bodies with antibiotics are of significant concern, with calls to monitor and control antibiotic pollution.

Selection in Natural Environments

Exposure to any one selective agent provides an advantage for the whole DNA element, simultaneously selecting for all genes on the element through “hitchhiking” by simple linkage. Exposure to heavy metals can coselect for antibiotic resistance when resistance genes are carried on mobile DNA elements that also carry genes for resistance to those heavy metals.

In environments containing diverse resistance elements and diverse selective agents, plasmids can acquire genes for resistance to multiple antibiotics, disinfectants, and metals and at the same time assemble genes for degradative pathways capable of acting upon other xenobiotics. For these reasons, aquatic environments are regarded as a natural reactor for the generation of novel xenogenetic DNA elements.

Generation of New DNA Elements and Newly Resistant Species

Pollution of natural environments with antibiotics and disinfectants affects community structure and leads to increased carriage of resistance genes in environmental organisms. It is now widely accepted that the natural environment is a recruitment ground for resistant organisms and potential opportunistic pathogens. Continued copulation with clinical integrons and selective agents will lead to an increased abundance of resistant cells in the general environment and place additional selective pressures on environmental organisms.

These secondary, unanticipated effects of the antibiotic revolution will precipitate evolutionary change among microorganisms across the globe and have potentially adverse consequences for human welfare.

Integrons as Tools for Biotechnology

Integrons have some significant advantages as a platform for biotechnological applications. They have all the machinery for acquisition, rearrangement, and expression of exogenous genes, in a tractable in vivo system. Natural integron integrase activity can be used to recover functional gene cassettes into a plasmid background for further downstream manipulation. Synthetic and natural gene cassettes can readily be introduced into cells via natural transformation.

This potentially allows any gene to be incorporated into an integron. Chromosomal cassette arrays are a vast resource for discovery of novel proteins and for the discovery of protein folds that might comprise building blocks for the flexible assembly of new proteins. Thus, integron platforms could be used to generate new biochemical pathways for bioremediation or biosynthesis through integron-mediated operon engineering.

Increasing Bacterial Evolvability

The use of antimicrobial compounds has driven the fixation of ever more complex DNA elements containing integrons, resistance genes, transposons, and other mobile DNAs within all human-dominated ecosystems. These xenogenetic DNA elements are released back into the environment, simultaneously with the antibiotics, disinfectants, and heavy metals that originally drove their selection.

Aquatic environments are likely to be major foci for complex interactions between integrons, resistance determinants, and mobile DNAs, where biofilms are a hot spot for genetic exchanges. Genetic diversity in bacteria is generated by mutation, recombination, and lateral gene transfer. Thus, an unintended consequence of the antibiotic revolution might be the fixation of bacterial lineages with inherently higher basal rates of mutation, recombination, and lateral gene transfer.

Conclusion

Integrons are remarkable genetic platforms with the ability to acquire, rearrange, and express diverse genes sampled from the microbial pangenome. Their facility for seamless acquisition of adaptive phenotypes brought them to sharp attention when they turned this activity toward disseminating antibiotic resistance among clinical pathogens.

They are an ancient, diverse, and widespread mechanism for generating genomic novelty and triggering adaptive responses in bacteria. Understanding their evolution and biology will inform both clinical practice and our ability to manage natural environments. There is potential for better health outcomes, better environmental management, and better understanding of the broad sweep of microbial evolution.