Improved annotation of antibiotic resistance determinants reveals microbial resistomes cluster by ecology

Gibson, Molly K.; Forsberg, Kevin J.; Dantas, Gautam

doi:10.1038/ismej.2014.106

Cited by 572 publications

(568 citation statements)

References 44 publications

(55 reference statements)

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“…Among MRGs, 19 types were all specifically enriched in different phyla, such as As in Firmicutes and Zn in Proteobacteria. Regarding the pathogenicity status, many more ARGs were enriched in pathogens compared with non-pathogens, which corresponded with the results of a previous HMM (hidden Markov model)-based ARG analysis (Gibson et al, 2015). Taken together, these results suggest a high-risk scenario of widespread antibiotic resistance in human pathogens.…”

Section: Resultssupporting

confidence: 78%

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

2016

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The high frequency of antibiotic resistance is a global public health concern. More seriously, widespread metal pressure in the environment may facilitate the proliferation of antibiotic resistance via coselection of antibiotic resistance genes (ARGs) and metal resistance genes (MRGs). Given the lack of comprehensive understanding of the ARG and MRG coselection, in this study both abundance relationship and genetic linkage between ARGs and MRGs were rigorously investigated by performing a genomic analysis of a large complete genome collection. Many more ARGs were enriched in human-associated bacteria compared with those subjected to less anthropogenic interference. The signatures of ARG and MRG co-occurrence were much more frequent and the distance linkages between ARGs and MRGs were much more intimate in human pathogens than those less human-associated bacteria. Moreover, the co-occurrence structures in the habitat divisions were significantly different, which could be attributed to their distinct gene transfer potentials. More exogenous ARGs and MRGs on the genomes of human pathogens indicated the importance of recent resistance acquisition in resistome development of human commensal flora. Overall, the study emphasizes the potential risk associated with ARG and MRG coselection of both environmental and medical relevance.

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Section: Resultssupporting

confidence: 78%

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

2016

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“…1). In total, 1,932 metagenomic fragments were assembled (N 50 of Ͼ1.35 kb) containing 2,283 ORFs which generally appeared unlike sequences deposited in public repositories, consistent with past observations from soil metagenomes (28,(46)(47)(48)(49)(50)(51). The average amino acid identity of all 2,283 ORFs to their closest homolog in the NCBI database was 52.7% Ϯ 19.0% (mean Ϯ standard deviation) (Fig.…”

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confidence: 50%

Identification of Genes Conferring Tolerance to Lignocellulose-Derived Inhibitors by Functional Selections in Soil Metagenomes

Forsberg

Patel

Witt

et al. 2016

Appl Environ Microbiol

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The production of fuels or chemicals from lignocellulose currently requires thermochemical pretreatment to release fermentable sugars. These harsh conditions also generate numerous small-molecule inhibitors of microbial growth and fermentation, limiting production. We applied small-insert functional metagenomic selections to discover genes that confer microbial tolerance to these inhibitors, identifying both individual genes and general biological processes associated with tolerance to multiple inhibitory compounds. Having screened over 248 Gb of DNA cloned from 16 diverse soil metagenomes, we describe gain-of-function tolerance against acid, alcohol, and aldehyde inhibitors derived from hemicellulose and lignin, demonstrating that uncultured soil microbial communities hold tremendous genetic potential to address the toxicity of pretreated lignocellulose. We recovered genes previously known to confer tolerance to lignocellulosic inhibitors as well as novel genes that confer tolerance via unknown functions. For instance, we implicated galactose metabolism in overcoming the toxicity of lignin monomers and identified a decarboxylase that confers tolerance to ferulic acid; this enzyme has been shown to catalyze the production of 4-vinyl guaiacol, a valuable precursor to vanillin production. These metagenomic tolerance genes can enable the flexible design of hardy microbial catalysts, customized to withstand inhibitors abundant in specific bioprocessing applications. Many lignocellulosic feedstocks (e.g., switchgrass) are preferred to maize, sugarcane, and other traditional food crops for the production of fuels and chemicals because they are able to grow on marginal land, often require little attention or energy input, and do not compete directly with the food supply (1-6). However, lignocellulose requires harsh thermochemical pretreatment methods to liberate fermentable monosaccharides (7-9), producing an additional compendium of compounds inhibitory to microbial growth that ultimately reduce production efficiencies (10-12). These small-molecule inhibitors derived from lignocellulose pretreatment (here called lignocellulosic inhibitors) are typically aldehydes, organic acids, furans, or phenolics and can originate from the cellulosic, hemicellulosic, and lignified fractions of the feedstock (11-15).Engineering hardier microbial production hosts with elevated tolerance to these inhibitors offers potential to ameliorate the toxic effects of these compounds without incurring the high process costs associated with detoxifying the lignocellulosic hydrolysate (16, 17). Unfortunately, the modes of toxicity of many of these toxins are poorly described, and genes conferring tolerance to many of these compounds have not been identified (18,19). An expanded catalog of tolerance-conferring genotypes may shed light on mechanisms of toxicity and enable synthetic biology approaches for the design of diverse production hosts with broadspectrum tolerance.Soil microorganisms, including white-rot fungi (20) and many bacteria (21), ar...

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“…It is also gaining interest in the field of clinical microbiology as a way to identify pathogens in normally sterile specimens (1)(2)(3)(4)(5)(6)(7). Not only does this approach allow for pathogen identification, but the gene content information can also be used for other analyses, such as antibiotic resistance prediction (8,9), typing for tracking of outbreaks or epidemiological studies (10), or assessment for other relevant genes, such as those encoding virulence factors (11,12).…”

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confidence: 99%

Impact of Contaminating DNA in Whole-Genome Amplification Kits Used for Metagenomic Shotgun Sequencing for Infection Diagnosis

et al. 2017

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Whole-genome amplification (WGA) is a useful tool for amplification of very small quantities of DNA for many uses, including metagenomic shotgun sequencing for infection diagnosis. Depending on the application, background DNA from WGA kits can be problematic. Three WGA kits were tested for their utility in a metagenomics approach to identify the pathogens in sonicate fluid comprised of biofilms and other materials dislodged from the surfaces of explanted prosthetic joints using sonication. The Illustra V2 Genomiphi, Illustra single cell Genomiphi, and Qiagen REPLI-g single cell kits were used to test identical sonicate fluid samples. Variations in the number of background reads, the genera identified in the background, and the number of reads from known pathogens known to be present in the samples were observed between kits. These results were then compared to those obtained with a library preparation without prior WGA using an NEBNext Ultra II paired-end kit, which requires a very small amount of input DNA. This approach also resulted in the presence of contaminant bacterial DNA and yielded fewer reads from the known pathogens. These findings highlight the impact that WGA kit selection can have on metagenomic analysis of low-biomass samples and the importance of the careful selection and consideration of the implications of using these tools.KEYWORDS metagenomics, prosthetic joint infection, whole-genome amplification M etagenomic shotgun sequencing is a rapidly developing powerful tool to examine microbial communities. It is also gaining interest in the field of clinical microbiology as a way to identify pathogens in normally sterile specimens (1-7). Not only does this approach allow for pathogen identification, but the gene content information can also be used for other analyses, such as antibiotic resistance prediction (8, 9), typing for tracking of outbreaks or epidemiological studies (10), or assessment for other relevant genes, such as those encoding virulence factors (11,12).One significant barrier to metagenomic shotgun sequencing approaches is the amount of genetic material necessary to perform these experiments. This is not an obstacle in settings such as fecal microbiome studies, where abundant organisms are present, but in other scenarios (e.g., in scenarios with low-biomass environmental samples and uncultured bacteria or in single cell analysis), the number of cells and the amount of genetic material can be limited (13)(14)(15)(16)(17). It is in these situations that whole-genome amplification (WGA) has the potential to play an important role in pathogen detection. Citation Thoendel M, Jeraldo P, GreenwoodQuaintance KE, Yao J, Chia N, Hanssen AD, Abdel MP, Patel R. 2017. Impact of contaminating DNA in whole-genome amplification kits used for metagenomic shotgun sequencing for infection diagnosis. J

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Improved annotation of antibiotic resistance determinants reveals microbial resistomes cluster by ecology

Cited by 572 publications

References 44 publications

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

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

Identification of Genes Conferring Tolerance to Lignocellulose-Derived Inhibitors by Functional Selections in Soil Metagenomes

Impact of Contaminating DNA in Whole-Genome Amplification Kits Used for Metagenomic Shotgun Sequencing for Infection Diagnosis

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