Gene cassettes encoding resistance to quaternary ammonium compounds: a role in the origin of clinical class 1 integrons?

Abstract

DNA sequencing, phylogenetic and mapping studies suggest that the class 1 integron found in pathogens arose when one member of the diverse family of environmental class 1 integrons became embedded into a Tn402 transposon. However, the timing of this event and the selective forces that first fixed the newly formed element in a bacterial lineage are still unknown. Biocides have a longer use in clinical practice than antibiotics, and a qac (quaternary ammonium compound) resistance gene, or remnant thereof, is a normal feature of class 1 integrons recovered from clinical isolates. Consequently, it is possible that the initial selective advantage was conferred by resistance to biocides, mediated by qac. Here, we show that diverse qac gene cassettes are a dominant feature of cassette arrays from environmental class 1 integrons, and that they occur in the absence of any antibiotic resistance gene cassettes. They are present in arrays that are dynamic, acquiring and rearranging gene cassettes within the arrays. The abundance of qac gene cassettes makes them a likely candidate for participation in the original insertion into Tn402, and as a source of a readily selectable phenotype. More broadly, the increasing use of qac and other biocides at the present time seems likely to promote the fixation of further novel genetic elements, with unpredictable and potentially adverse consequences for human health and agriculture.

Quantitative and qualitative impact of hospital effluent on dissemination of the integron pool

“…Global sludge stress constitutes an ideal system for activation of the SOS response, leading to continuous IntI expression and, thus, to a high rate of gene cassette rearrangement via excision, increasing the probability of empty RIs. The normalized copy number of integrons in the discharged river water was similar to that found in previous studies (Hardwick et al, 2008;Gillings et al, 2008b;Wright et al, 2008;Rosewarne et al, 2010), in which bacteria harboring class 1 integrons represented between 1% and 10% of total bacteria in various environmental samples. These low values seem to represent the basal integron background occurring naturally in bacterial communities not subjected to anthropogenic activities.…”

“…Hospital effluent impact on integron dissemination T Stalder et al be involved in class 1 integron dissemination (Gaze et al, 2005;Gillings et al, 2008b;Gaze et al, 2011). Surprisingly, we detected few qac gene cassettes in the gene cassette arrays in the hospital effluent.…”

“…Indeed, they were associated in the pre-antibiotic era with diverse plasmids or transposons (such as Tn21) that are widespread in environmental bacteria and contain QAC-resistance or mercury-resistance determinants. Exposure to heavy metals and QACs may have exerted selective pressure, enriching bacterial communities with integrons, before the antibiotic era (Gillings et al, 2008b;Rosewarne et al, 2010;Stokes and Gillings, 2011).…”

“…Because 5 0 CS and 3 0 CS primers could target nonspecific sites on metagenomic DNA, clones were controlled by PCR with the internal primer MRG284 (Gillings et al, 2008b) adjacent to the 5 0 CS primer hybridization site, coupled to the 3 0 CS primer (see Supplementary Information). The PCR product includes 97 base pairs (bp) of the attI region (5 0 conserved segment) and 56 bp of the 3 0 conserved segment.…”

MOLECULAR DETECTION OF ANTIBIOTIC-RESISTANCE DETERMINANTS INESCHERICHIA COLIISOLATED FROM THE ENDANGERED AUSTRALIAN SEA LION (NEOPHOCA CINEREA)

“…Amplicons will vary in size, depending on the number and types of gene cassettes that are present. The intI1-positive samples that failed to amplify using HS458 and HS459 were screened using the primers MRG284 and MRG285 (Gillings et al 2009) using PCR conditions as described for HS458 and HS459 primers except for the annealing temperature and time, which were increased to 65 C for 2 min.…”