Evolution of class 1 integrons: Mobilization and dispersal via food-borne bacteria

Abstract

Class 1 integrons have played a major role in the global dissemination of antibiotic resistance. Reconstructing the history of class 1 integrons might help us control further spread of antibiotic resistance by understanding how human activities influence microbial evolution. Here we describe a class 1 integron that represents an intermediate stage in the evolutionary history of clinical integrons. It was embedded in a series of nested transposons, carried on an IncP plasmid resident in Enterobacter, isolated from the surface of baby spinach leaves. Based on the structure of this integron, we present a modified hypothesis for integron assembly, where the ancestral clinical class 1 integron was captured from a betaproteobacterial chromosome to form a Tn402-like transposon. This transposon then inserted into a plasmid-borne Tn21-like ancestor while in an environmental setting, possibly a bacterium resident in the phyllosphere. We suggest that the qacE gene cassette, conferring resistance to biocides, together with the mercury resistance operon carried by Tn21, provided a selective advantage when this bacterium made its way into the human commensal flora via food. The integron characterized here was located in Tn6007, which along with Tn6008, forms part of the larger Tn6006 transposon, itself inserted into another transposable element to form the Tn21-like transposon, Tn6005. This element has previously been described from the human microbiota, but with a promoter mutation that upregulates integron cassette expression. This element we describe here is from an environmental bacterium, and supports the hypothesis that the ancestral class 1 integron migrated into anthropogenic settings via foodstuffs. Selection pressures brought about by early antimicrobial agents, including mercury, arsenic and disinfectants, promoted its initial fixation, the acquisition of promoter mutations, and subsequent dissemination into various species and pathogens.

High diversity and rapid spatial turnover of integron gene cassettes in soil

“…Integron gene cassettes appear to be ubiquitous, having been recovered from every environment surveyed, including soil and aquatic sediments, the microbiota of plants and animals, aquatic biofilms, seawater and deep-sea hydrothermal vents (Goldstein et al, 2001;Gillings et al, 2005;Elsaied et al, 2007;Gillings et al, 2009;Bailey et al, 2010;Elsaied et al, 2011;Ghaly et al, 2017). Further, in silico analysis has detected integron gene cassettes in the sequenced genomes of a range of major bacterial taxa, including γ-Proteobacteria, β-Proteobacteria, Spirochaetes, Chloroflexi, Chlorobi and Planctomycetes (Cury et al, 2016).…”

Microbiological Safety and Antibiogram Analysis of Selected Food Products Obtained in the Marketplace of Peshawar and Mardan, KPK, Pakistan

“…It is a main community health risk [19,20]. At the same time, these organisms have been isolated from an extensive variety of foodstuffs consumed by man [21,22]. Therefore, the current study was designed to evaluate various foods for the detection of bacterial and fungal contaminants and their susceptibility assessment towards the selected antibiotics and antifungals commonly available in the market.…”

Prevalence of class 1 integron in Escherichia coli isolated from animal sources in Iran: a systematic review and meta-analysis

“…In recent years, different acquired resistance mechanisms, including bacteriophages, transposons, plasmids, and integrons, have been identified involving the spread of resistance genes in the bacteria [10]. Among the genetic elements, integrons may also contribute to the widespread incidence and spread of antibiotic resistance [11]. These elements are capable of capturing, integrating, and mobilizing antibiotic resistant gene cassettes.…”