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Background Antibacterial 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. Results Co-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. Conclusions This 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.

\"For almost four billion years, microbes had the primordial oceans all to themselves. The stewards of Earth, these organisms transformed the chemistry of our planet to make it habitable for plants, animals, and us. Life's Engines takes readers deep into the microscopic world to explore how these marvelous creatures made life on Earth possible--and how human life today would cease to exist without them. Paul Falkowski looks \"under the hood\" of microbes to find the engines of life, the actual working parts that do the biochemical heavy lifting for every living organism on Earth. With insight and humor, he explains how these miniature engines are built--and how they have been appropriated by and assembled like Lego sets within every creature that walks, swims, or flies. Falkowski shows how evolution works to maintain this core machinery of life, and how we and other animals are veritable conglomerations of microbes. A vibrantly entertaining book about the microbes that support our very existence, Life's Engines will inspire wonder about these elegantly complex nanomachines that have driven life since its origin. It also issues a timely warning about the dangers of tinkering with that machinery to make it more \"efficient\" at meeting the ever-growing demands of humans in the coming century.\"--Jacket.

Current-day metagenomics analyses increasingly involve de novo taxonomic classification of long DNA sequences and metagenome-assembled genomes. Here, we show that the conventional best-hit approach often leads to classifications that are too specific, especially when the sequences represent novel deep lineages. We present a classification method that integrates multiple signals to classify sequences (Contig Annotation Tool, CAT) and metagenome-assembled genomes (Bin Annotation Tool, BAT). Classifications are automatically made at low taxonomic ranks if closely related organisms are present in the reference database and at higher ranks otherwise. The result is a high classification precision even for sequences from considerably unknown organisms.

A metagenomic approach and network analysis was used to investigate the wide-spectrum profiles of antibiotic resistance genes (ARGs) and their co-occurrence patterns in 50 samples from 10 typical environments. In total, 260 ARG subtypes belonging to 18 ARG types were detected with an abundance range of 5.4 × 10 −6 –2.2 × 10 −1 copy of ARG per copy of 16S-rRNA gene. The trend of the total ARG abundances in environments matched well with the levels of anthropogenic impacts on these environments. From the less impacted environments to the seriously impacted environments, the total ARG abundances increased up to three orders of magnitude, that is, from 3.2 × 10 −3 to 3.1 × 10 0 copy of ARG per copy of 16S-rRNA gene. The abundant ARGs were associated with aminoglycoside, bacitracin, β-lactam, chloramphenicol, macrolide-lincosamide-streptogramin, quinolone, sulphonamide and tetracycline, in agreement with the antibiotics extensively used in human medicine or veterinary medicine/promoters. The widespread occurrences and abundance variation trend of vancomycin resistance genes in different environments might imply the spread of vancomycin resistance genes because of the selective pressure resulting from vancomycin use. The simultaneous enrichment of 12 ARG types in adult chicken faeces suggests the coselection of multiple ARGs in this production system. Non-metric multidimensional scaling analysis revealed that samples belonging to the same environment generally possessed similar ARG compositions. Based on the co-occurrence pattern revealed by network analysis, tet M and aminoglycoside resistance protein, the hubs of the ARG network, are proposed to be indicators to quantitatively estimate the abundance of 23 other co-occurring ARG subtypes by power functions.

Antibiotic resistance is a severe global threat for public health, causing around 700,000 deaths per year. Horizontal gene transfer (HGT) is one of the most significant pathways to disseminate antibiotic resistance. It is commonly acknowledged that sub-minimum inhibition concentrations of antibiotics are major contributors in promoting antibiotic resistance through HGT. Pharmaceuticals are occurring in our environments at increased levels, yet little is known whether non-antibiotic pharmaceuticals cause or accelerate the dissemination of antibiotic resistance. Here, we report for the first time that the antiepileptic drug, carbamazepine, promotes conjugative transfer of antibiotic resistance genes. It was seen that environmentally relevant concentrations of carbamazepine (e.g., 0.05 mg/L) significantly enhanced the conjugative transfer of multiresistance genes carried by plasmid within and across bacterial genera. The underlying mechanisms of the enhanced HGT were revealed by detecting oxidative stress and cell membrane permeability, in combination with MinION DNA sequencing, genome-wide RNA sequencing, and proteomic analysis. Carbamazepine induced a series of acute responses, including increased levels of reactive oxygen species, the SOS response; increased cell membrane permeability, and pilus generation. Expressional levels of genes related to these processes were significantly upregulated during carbamazepine exposure. Given that HGT occurs widely among different species in various environments, these findings are an early warning for a wide assessment of the roles of non-antibiotic pharmaceuticals in the spread of antibiotic resistance.

Background Horizontal gene transfer (HGT), which is affected by environmental pollution and climate change, promotes genetic communication, changing bacterial pathogenicity and drug resistance. However, few studies have been conducted on the effect of HGT on the high pathogenicity and drug resistance of the opportunistic pathogen Vibrio harveyi . Results V. harveyi 345 that was multidrug resistant and infected Epinephelus oanceolutus was isolated from a diseased organism in Shenzhen, Southern China, an important and contaminated aquaculture area. Analysis of the entire genome sequence predicted 5678 genes including 487 virulence genes contributing to bacterial pathogenesis and 25 antibiotic-resistance genes (ARGs) contributing to antimicrobial resistance. Five ARGs ( tetm , tetb , qnrs , dfra17 , and sul2 ) and one virulence gene (CU052_28670) on the pAQU-type plasmid p345–185, provided direct evidence for HGT. Comparative genome analysis of 31  V. harveyi strains indicated that 217 genes and 7 gene families, including a class C beta-lactamase gene, a virulence-associated protein D gene, and an OmpA family protein gene were specific to strain V. harveyi 345. These genes could contribute to HGT or be horizontally transferred from other bacteria to enhance the virulence or antibiotic resistance of 345. Mobile genetic elements in 71 genomic islands encoding virulence factors for three type III secretion proteins and 13 type VI secretion system proteins, and two incomplete prophage sequences were detected that could be HGT transfer tools. Evaluation of the complete genome of V. harveyi 345 and comparative genomics indicated genomic exchange, especially exchange of pathogenic genes and drug-resistance genes by HGT contributing to pathogenicity and drug resistance. Climate change and continued environmental deterioration are expected to accelerate the HGT of V. harveyi , increasing its pathogenicity and drug resistance. Conclusion This study provides timely information for further analysis of V. harveyi pathogenesis and antimicrobial resistance and developing pollution control measurements for coastal areas.

Background Excesses of antibiotic resistance genes (ARGs), which are regarded as emerging environmental pollutants, have been observed in various environments. The incidence of ARGs in drinking water causes potential risks to human health and receives more attention from the public. However, ARGs harbored in drinking water remain largely unexplored. In this study, we aimed at establishing an antibiotic resistome catalogue in drinking water samples from a wide range of regions and to explore the potential hosts of ARGs. Results A catalogue of antibiotic resistome in drinking water was established, and the host-tracking of ARGs was conducted through a large-scale survey using metagenomic approach. The drinking water samples were collected at the point of use in 25 cities in mainland China, Hong Kong, Macau, Taiwan, South Africa, Singapore and the USA. In total, 181 ARG subtypes belonging to 16 ARG types were detected with an abundance range of 2.8 × 10 −2 to 4.2 × 10 −1 copies of ARG per cell. The highest abundance was found in northern China (Henan Province). Bacitracin, multidrug, aminoglycoside, sulfonamide, and beta-lactam resistance genes were dominant in drinking water. Of the drinking water samples tested, 84% had a higher ARG abundance than typical environmental ecosystems of sediment and soil. Metagenomic assembly-based host-tracking analysis identified Acidovorax , Acinetobacter , Aeromonas , Methylobacterium , Methyloversatilis , Mycobacterium , Polaromonas , and Pseudomonas as the hosts of ARGs. Moreover, potential horizontal transfer of ARGs in drinking water systems was proposed by network and Procrustes analyses. Conclusions The antibiotic resistome catalogue compiled using a large-scale survey provides a useful reference for future studies on the global surveillance and risk management of ARGs in drinking water. Graphical abstract .

Secondary metabolites (SM) produced by fungi and bacteria have long been of exceptional interest owing to their unique biomedical ramifications. The traditional discovery of new natural products that was mainly driven by bioactivity screening has now experienced a fresh new approach in the form of genome mining. Several bioinformatics tools have been continuously developed to detect potential biosynthetic gene clusters (BGCs) that are responsible for the production of SM. Although the principles underlying the computation of these tools have been discussed, the biological background is left underrated and ambiguous. In this review, we emphasize the biological hypotheses in BGC formation driven from the observations across genomes in bacteria and fungi, and provide a comprehensive list of updated algorithms/tools exclusively for BGC detection. Our review points to a direction that the biological hypotheses should be systematically incorporated into the BGC prediction and assist the prioritization of candidate BGC.

Mining is among the human activities with widest environmental impacts, and mining-impacted environments are characterized by high levels of metals that can co-select for antibiotic resistance genes (ARGs) in microorganisms. However, ARGs in mining-impacted environments are still poorly understood. Here, we conducted a comprehensive study of ARGs in such environments worldwide, taking advantage of 272 metagenomes generated from a global-scale data collection and two national sampling efforts in China. The average total abundance of the ARGs in globally distributed studied mine sites was 1572 times per gigabase, being rivaling that of urban sewage but much higher than that of freshwater sediments. Multidrug resistance genes accounted for 40% of the total ARG abundance, tended to co-occur with multimetal resistance genes, and were highly mobile (e.g. on average 16% occurring on plasmids). Among the 1848 high-quality metagenome-assembled genomes (MAGs), 85% carried at least one multidrug resistance gene plus one multimetal resistance gene. These high-quality ARG-carrying MAGs considerably expanded the phylogenetic diversity of ARG hosts, providing the first representatives of ARG-carrying MAGs for the Archaea domain and three bacterial phyla. Moreover, 54 high-quality ARG-carrying MAGs were identified as potential pathogens. Our findings suggest that mining-impacted environments worldwide are underexplored hotspots of multidrug resistance genes.