Linking the resistome and plasmidome to the microbiome

Stalder, Thibault; Press, Maximilian O.; Sullivan, Shawn; Liachko, Ivan; Top, Eva M.

doi:10.1038/s41396-019-0446-4

Cited by 207 publications

(204 citation statements)

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“…In addition, distinct populations that are in close proximity in the input sample and repeat sequences may yield misleading contact signals and result in chimeric assemblies (Marbouty and Koszul 2015). Nevertheless, the application of proximity ligation strategies to naturally occurring complex microbial consortia can provide important insights (Bickhart et al 2019;Stalder et al 2019).…”

Section: Chromosome Conformation Capture Methodsmentioning

confidence: 99%

Accurate and complete genomes from metagenomes

et al. 2020

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Genomes are an integral component of the biological information about an organism; thus, the more complete the genome, the more informative it is. Historically, bacterial and archaeal genomes were reconstructed from pure (monoclonal) cultures, and the first reported sequences were manually curated to completion. However, the bottleneck imposed by the requirement for isolates precluded genomic insights for the vast majority of microbial life. Shotgun sequencing of microbial communities, referred to initially as community genomics and subsequently as genome-resolved metagenomics, can circumvent this limitation by obtaining metagenome-assembled genomes (MAGs); but gaps, local assembly errors, chimeras, and contamination by fragments from other genomes limit the value of these genomes. Here, we discuss genome curation to improve and, in some cases, achieve complete (circularized, no gaps) MAGs (CMAGs). To date, few CMAGs have been generated, although notably some are from very complex systems such as soil and sediment. Through analysis of about 7000 published complete bacterial isolate genomes, we verify the value of cumulative GC skew in combination with other metrics to establish bacterial genome sequence accuracy. The analysis of cumulative GC skew identified potential misassemblies in some reference genomes of isolated bacteria and the repeat sequences that likely gave rise to them. We discuss methods that could be implemented in bioinformatic approaches for curation to ensure that metabolic and evolutionary analyses can be based on very high-quality genomes.

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Section: Chromosome Conformation Capture Methodsmentioning

confidence: 99%

Accurate and complete genomes from metagenomes

et al. 2020

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“…Considering that the expression of mobile genetic elements such as integrons is a robust strategy of genetic interchange and one of the main drivers of bacterial evolution [43], we speculate that the expression of plasmid-associated ARGs has functions other than transferring antimicrobial resistance in the rumen. Recently, a wide range of bacterial hosts of plasmids in wastewater samples has been revealed by analyzing Hi-C and shotgun metagenomic data [44]. Those approaches can also be applied to investigate plasmid-associated ARG as well as their bacterial host in cattle, which may help understand the contribution of plasmids to the transmission of AMR determinants in the rumen.…”

Section: Discussionmentioning

confidence: 99%

Host genetics affected the resistome and its expression patterns in the rumen of beef cattle raised without antibiotics used in humans

Ma¹,

Li²,

Zaheer³

et al. 2020

Preprint

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Background: The rumen microbiome is a potential reservoir of antimicrobial-resistant genes (ARGs), termly resistome. However, the activity of ARGs and what factors affect expression of ARGs in the rumen is unknown. Here, the rumen resistome was evaluated using metagenomic and metatranscriptomic datasets, with the aim to identify the active rumen resistome and whether it can be affected by cattle breed and feed efficiency.Results: Genes encoding resistance to 12 ARG classes representing 62 individual ARGs were detected in the rumen metagenomes of Angus, Charolais or Kinsella composite hybrid (KC) beef steers (n = 48) with high and low feed efficiency. Three genes encoding tetracycline (tetQ, tetW) and macrolide (mefA) resistance constituted 75.3% of abundance of total ARGs identified in all animals, suggesting they are ‘core’ resistome in the rumen of steers. Only about 20.96% (13/62) of the total ARGs identified were expressed, among which genes encoding resistance to tetracycline, macrolide-licosamide-streptogramin (MLS), aminoglycoside, and multidrug exhibited the highest level of expression. More than half (56.2%) of the ARGs identified were plasmid-associated, while only 5 plasmid-associated ARGs were expressed. The abundance of 17, 14, and 5 individual ARGs were significantly affected by breed, feed efficiency, and breed × feed efficiency, respectively, while the expression of ARGs did not differ among breeds or between feed efficiency groups. In KC cattle, less number of total ARGs, ARG transcripts, as well as total active bacteria (estimated by 16S rRNA copies) was observed than AN. The total active bacteria were negatively correlated with expression of MLS and tetracycline ARG (mefA, tet40, tetM, tetW, and an unidentified tet), and tended to be negatively correlated with the expression of plasmid-associated tetracycline ARG t only in the rumen of KC cattle.Conclusions: Our results suggest that a large portion of the ARGs are not expressed in the rumen of cattle raised without antibiotics used in humans. The identified less diversified active resistome and total active bacteria, and the significant correlation between total active bacteria and the abundance of ARG transcripts in KC cattle suggest that the expression of resistome in the rumen may be breed specific and driven by ruminal microbiota.

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“…The basis for the concern of vector DNA, generally plasmids, and selectable marker genes for antibiotic resistance, appears to be about their potential expression in GM host cells. Since antibiotic genes in the environment are a concern [98,99] , the question becomes what happens when people consume such genes from a GM animal (or plant). The answer from two decades ago in the context of transgenic fish [100] is that antibiotic resistance will not be passed on to the consumer for three reasons.…”

Section: Concerns Of Plasmid and Prokaryotic Dna Sequence Contaminationmentioning

confidence: 99%

Regulatory issues for genetically modified animals

Hackett

2020

Front. Agr. Sci. Eng.

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Precision genetics and breeding have the potential to meet the agricultural needs and goals of the world in the 21st century. These needs include increasing the efficiency of production of animals and improving their products with minimal impact on the environment. The USA is the major innovator in genomic science and the acknowledged leader in formulating policies to regulate genetic applications in medicine and agriculture. However, governments worldwide have been exceedingly reluctant to support the introduction of genetically modified (GM) animals into agriculture. Regulatory policies have stagnated due to legal guidelines that could not anticipate the needs and solutions that are evident today. This must change if we are to maintain planetary integrity. I propose a new, market-based regulatory model for GM livestock that has both a strong scientific foundation and has worked for 10000 years. The model is similar to that for information technology in which specific algorithms drive computer and cell phone applications. Genome engineers write genetic algorithms that drive the traits in biological organisms. Accordingly, GM products should be viewed in terms of their use and public benefit rather than by limitations to the genetic programing coming from a few highly vocal groups. Genetic algorithms (Genapps) of the 21st century will include not only introduction of synthetic genes, but also complete natural and synthetic biochemical pathways to produce agricultural products that are maximally efficient, healthy to humans and animals, and sustainable in an era of changing climates while avoiding environmental degradation.

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Linking the resistome and plasmidome to the microbiome

Cited by 207 publications

References 47 publications

Accurate and complete genomes from metagenomes

Accurate and complete genomes from metagenomes

Host genetics affected the resistome and its expression patterns in the rumen of beef cattle raised without antibiotics used in humans

Regulatory issues for genetically modified animals

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