Co-occurrence of resistance genes to antibiotics, biocides and metals reveals novel insights into their co-selection potential

Abstract

BackgroundAntibacterial biocides and metals can co-select for antibiotic resistance when bacteria harbour resistance or tolerance genes towards both types of compounds. Despite numerous case studies, systematic and quantitative data on co-occurrence of such genes on plasmids and chromosomes is lacking, as is knowledge on environments and bacterial taxa that tend to carry resistance genes to such compounds. This effectively prevents identification of risk scenarios. Therefore, we aimed to identify general patterns for which biocide/metal resistance genes (BMRGs) and antibiotic resistance genes (ARGs) that tend to occur together. We also aimed to quantify co-occurrence of resistance genes in different environments and taxa, and investigate to what extent plasmids carrying both types of genes are conjugative and/or are carrying toxin-antitoxin systems.ResultsCo-occurrence patterns of resistance genes were derived from publicly available, fully sequenced bacterial genomes (n = 2522) and plasmids (n = 4582). The only BMRGs commonly co-occurring with ARGs on plasmids were mercury resistance genes and the qacE∆1 gene that provides low-level resistance to quaternary ammonium compounds. Novel connections between cadmium/zinc and macrolide/aminoglycoside resistance genes were also uncovered. Several clinically important bacterial taxa were particularly prone to carry both BMRGs and ARGs. Bacteria carrying BMRGs more often carried ARGs compared to bacteria without (p < 0.0001). BMRGs were found in 86 % of bacterial genomes, and co-occurred with ARGs in 17 % of the cases. In contrast, co-occurrences of BMRGs and ARGs were rare on plasmids from all external environments (<0.7 %) but more common on those of human and domestic animal origin (5 % and 7 %, respectively). Finally, plasmids with both BMRGs and ARGs were more likely to be conjugative (p < 0.0001) and carry toxin-antitoxin systems (p < 0.0001) than plasmids without resistance genes.ConclusionsThis is the first large-scale identification of compounds, taxa and environments of particular concern for co-selection of resistance against antibiotics, biocides and metals. Genetic co-occurrences suggest that plasmids provide limited opportunities for biocides and metals to promote horizontal transfer of antibiotic resistance through co-selection, whereas ample possibilities exist for indirect selection via chromosomal BMRGs. Taken together, the derived patterns improve our understanding of co-selection potential between biocides, metals and antibiotics, and thereby provide guidance for risk-reducing actions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-2153-5) contains supplementary material, which is available to authorized users.

Co-occurrence of antibiotic and metal resistance genes revealed in complete genome collection

“…Among the 23 MRG types detected, Zn, Cu, Ni, Mn and Hg resistance genes accounted for more than half (60%) of the total MRGs retrieved. Generally, the resistance genes for commonly consumed antibiotics and metals are more likely to be present in high abundance, which also has been demonstrated in the previous abundance-based surveys (Li et al, 2015;Pal et al, 2015).…”

“…The above observed ARG and MRG abundance profiles within the genome collection, plus previous sporadic studies on coresistance in pathogens (Gillings et al, 2015;Wales and Davies, 2015;Di Cesare et al, 2016;Johnson et al, 2016) and the recently reported abundance correlation in clinically important genera (e.g., Escherichia, Shigella and Klebsiella) (Pal et al, 2015) kindled our interest in thoroughly investigating their possible physical genetic co-occurrence, particularly in humanassociated bacteria. Therefore, two concepts, the incidence of encountering ARGs along the distance from MRGs and their average minimum distance (MetA min ), were used to further evaluate the possible risk associated with ARG and MRG coselection by examining their likeliness of co-occurrence on Figure 1 Presence and absence of ARGs and MRGs in the complete genome collection.…”

Fate of antibiotic resistance genes and its drivers during anaerobic co-digestion of food waste and sewage sludge based on microwave pretreatment

“…sulfonamides, betalactams, amphenicols, tetracyclines and aminoglycosides, and certain bacterial taxa comprising many pathogens were particularly prone to carrying both MRGs and ARGs, highlighting the potential clinical consequences of co-selection (Pal et al, 2015). However, the bio-availability should be taken into account concerning the co-selection of heavy metals, because it is the bioavailable fractions of heavy metals that impose selective pressure on microbes.…”

“…It may also contribute to the enhancement of ARGs reduction, and this deserves to be elucidated. The co-occurrence of antibiotic and metal resistance in bacteria has been widely observed (Pal et al, 2015), which is caused by the cross-or co-resistance phenomena. Cross-resistance occurs when the same mechanism reduces the susceptibility to metals and antibiotics simultaneously, and co-resistance occurs when separate resistance genes are situated on the same genetic element (Pal et al, 2015).…”

“…The co-occurrence of antibiotic and metal resistance in bacteria has been widely observed (Pal et al, 2015), which is caused by the cross-or co-resistance phenomena. Cross-resistance occurs when the same mechanism reduces the susceptibility to metals and antibiotics simultaneously, and co-resistance occurs when separate resistance genes are situated on the same genetic element (Pal et al, 2015). This fact may be of great importance in the case of SS, because it both contains significant amounts of heavy metals and antibiotics (Bondarczuk et al, 2016;Le-minh et al, 2010).…”