CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database
TL;DR: A new Resistomes & Variants module provides analysis and statistical summary of in silico predicted resistance variants from 82 pathogens and over 100 000 genomes, able to summarize predicted resistance using the information included in CARD, identify trends in AMR mobility and determine previously undescribed and novel resistance variants.
Abstract: The Comprehensive Antibiotic Resistance Database (CARD; https://card.mcmaster.ca) is a curated resource providing reference DNA and protein sequences, detection models and bioinformatics tools on the molecular basis of bacterial antimicrobial resistance (AMR). CARD focuses on providing high-quality reference data and molecular sequences within a controlled vocabulary, the Antibiotic Resistance Ontology (ARO), designed by the CARD biocuration team to integrate with software development efforts for resistome analysis and prediction, such as CARD's Resistance Gene Identifier (RGI) software. Since 2017, CARD has expanded through extensive curation of reference sequences, revision of the ontological structure, curation of over 500 new AMR detection models, development of a new classification paradigm and expansion of analytical tools. Most notably, a new Resistomes & Variants module provides analysis and statistical summary of in silico predicted resistance variants from 82 pathogens and over 100 000 genomes. By adding these resistance variants to CARD, we are able to summarize predicted resistance using the information included in CARD, identify trends in AMR mobility and determine previously undescribed and novel resistance variants. Here, we describe updates and recent expansions to CARD and its biocuration process, including new resources for community biocuration of AMR molecular reference data.
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TL;DR: Wang et al. as mentioned in this paper performed a comparative metagenomic analysis to survey taxonomic, functional levels, and microbial communities' genome content in healthy women's vaginal microbiome, including all dominant vaginal Lactobacillus species, such as L. iners, A. crispatus, L. gasseri, and L. jensenii.
6 citations
TL;DR: In this paper, the plasmid-associated resistance gene encoding the AAC(6')-Ib-cr enzyme that inactivates the fluoroquinolone antibiotic ciprofloxacin is present in >70% of strains from the most rapidly expanding subgroup of multidrug resistant Escherichia coli ST131.
Abstract: Escherichia coli ST131 is a recently emerged antibiotic resistant clone responsible for high rates of urinary tract and bloodstream infections. Despite its global dominance, the precise mechanisms that have driven the rapid dissemination of ST131 remain unknown. Here, we show that the plasmid-associated resistance gene encoding the AAC(6')-Ib-cr enzyme that inactivates the fluoroquinolone antibiotic ciprofloxacin is present in >70% of strains from the most rapidly expanding subgroup of multidrug resistant ST131. Using a series of genome-edited and plasmid-cured isogenic strains, we demonstrate that the aac(6')-Ib-cr gene confers a selective advantage on ST131 in the presence of ciprofloxacin, even in strains containing chromosomal GyrA and ParC FQ-resistance mutations. Further, we identify a pattern of emerging carbapenem resistance in other common E. coli clones carrying both aac(6')-Ib-cr and chromosomal FQ-resistance mutations, suggesting this dual resistance combination may also impart a selective advantage on these non-ST131 antibiotic resistant lineages.
6 citations
TL;DR: A systematic resistance evolution study of the ESKAPE pathogens suggests that collateral responses may be preserved across species and may help extend the contribution of previous collateral network studies in the development of treatment strategies to address the problem of antibiotic resistance.
Abstract: As drug resistance continues to grow, treatment strategies that turn resistance into a disadvantage for the organism will be increasingly relied upon to treat infections and to lower the rate of multidrug resistance. The majority of work in this area has investigated how resistance evolution toward a single antibiotic effects a specific organism’s collateral response to a wide variety of antibiotics. The results of these studies have been used to identify networks of drugs which can be used to drive resistance in a particular direction. However, little is known about the extent of evolutionary conservation of these responses across species. We sought to address this knowledge gap by performing a systematic resistance evolution study of the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae) under uniform growth conditions using five clinically relevant antibiotics with diverse modes of action. Evolved lineages were analyzed for collateral effects and the molecular mechanisms behind the observed phenotypes. Fourteen universal cross-resistance and two global collateral sensitivity relationships were found among the lineages. Genomic analyses revealed drug-dependent divergent and conserved evolutionary trajectories among the pathogens. Our findings suggest that collateral responses may be preserved across species. These findings may help extend the contribution of previous collateral network studies in the development of treatment strategies to address the problem of antibiotic resistance.
6 citations
Cites background from "CARD 2020: antibiotic resistome sur..."
...The mutations shown were found in genes associated with resistance determinants as defined by the Comprehensive Antibiotic Resistance Database (CARD) (71)....
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TL;DR: In this paper, the vancomycin-resistant enterococci (VRE) was detected in 6 (3.1%) of 191 water samples collected near treated wastewater discharge sites.
Abstract: Objectives The global dissemination of vancomycin-resistant enterococci (VRE) has become a serious public-health concern. Although outbreaks are typically caused by nosocomial transmission, contaminated food and water may contribute to the spread of VRE. The aim of this study was to assess the presence of VRE in flowing surface water bodies in Switzerland and to characterise the isolates. Methods Surface water was sampled from rivers, streams and canals throughout Switzerland and was screened for the presence of VRE. Whole-genome sequencing was used to identify antimicrobial resistance genes and the phylogenetic similarity of the obtained isolates. Results VRE were detected in 6 (3.1%) of 191 water samples. The six VRE-containing samples were all collected near treated wastewater discharge sites. The six isolates were identified as Enterococcus faecium sequence type 133 (ST133) and harboured the vancomycin resistance-conferring vanA gene cluster on transposon Tn1546. They showed a close phylogenetic relationship to ST133 swine faecal isolates obtained during a previously reported screening in Switzerland. Conclusion Our results suggest that surface water contributes to the environmental dissemination of VRE. Repeated identification of ST133 clones in geographically distinct water sampling sites and swine faecal samples collected in slaughterhouses may indicate a local dominance of this VRE lineage in Switzerland.
6 citations
01 Oct 2022
TL;DR: Wang et al. as mentioned in this paper conducted a comprehensive literature review to summarize the epidemiological, environmental, and molecular evidence of indoor microbiome studies, and found that the potential protective indoor microorganisms for asthma are mainly from the phyla Actinobacteria and Proteobacteria, and the risk microorganisms are from Bacilli, Clostridia, and Bacteroidia.
Abstract: The prevalence of allergic diseases, such as asthma, rhinitis, eczema, and sick-building syndrome (SBS), has increased drastically in the past few decades. Current medications can only relieve the symptoms but not cure these diseases whose development is suggested to be greatly impacted by the indoor microbiome. However, no study comprehensively summarizes the progress and general rules in the field, impeding subsequent translational application. To close knowledge gaps between theoretical research and practical application, we conducted a comprehensive literature review to summarize the epidemiological, environmental, and molecular evidence of indoor microbiome studies. Epidemiological evidence shows that the potential protective indoor microorganisms for asthma are mainly from the phyla Actinobacteria and Proteobacteria, and the risk microorganisms are mainly from Bacilli, Clostridia, and Bacteroidia. Due to extremely high microbial diversity and geographic variation, different health-associated species/genera are detected in different regions. Compared with indoor microbial composition, indoor metabolites show more consistent associations with health, including microbial volatile organic compounds (MVOCs), lipopolysaccharides (LPS), indole derivatives, and flavonoids. Therefore, indoor metabolites could be a better indicator than indoor microbial taxa for environmental assessments and health outcome prediction. The interaction between the indoor microbiome and environmental characteristics (surrounding greenness, relative humidity, building confinement, CO 2 concentration) and immunology effects of indoor microorganisms (inflammatory cytokines, pattern recognition receptors) are briefly reviewed to provide new insights for disease prevention and treatment. Widely used tools in indoor microbiome studies are introduced to facilitate standard practice and the precise identification of health-related targets.
6 citations
References
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TL;DR: A new approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair (MSP) score.
88,255 citations
"CARD 2020: antibiotic resistome sur..." refers background in this paper
...The latter is described by CARD’s Model Ontology (MO, Supplementary Figure S1), which includes reference nucleotide and protein sequences, as well as additional search parameters including mutations conferring AMR (if applicable) and curated BLAST(P/N) (34,35) bit score cut-offs....
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TL;DR: Burrows-Wheeler Alignment tool (BWA) is implemented, a new read alignment package that is based on backward search with Burrows–Wheeler Transform (BWT), to efficiently align short sequencing reads against a large reference sequence such as the human genome, allowing mismatches and gaps.
Abstract: Motivation: The enormous amount of short reads generated by the new DNA sequencing technologies call for the development of fast and accurate read alignment programs. A first generation of hash table-based methods has been developed, including MAQ, which is accurate, feature rich and fast enough to align short reads from a single individual. However, MAQ does not support gapped alignment for single-end reads, which makes it unsuitable for alignment of longer reads where indels may occur frequently. The speed of MAQ is also a concern when the alignment is scaled up to the resequencing of hundreds of individuals.
Results: We implemented Burrows-Wheeler Alignment tool (BWA), a new read alignment package that is based on backward search with Burrows–Wheeler Transform (BWT), to efficiently align short sequencing reads against a large reference sequence such as the human genome, allowing mismatches and gaps. BWA supports both base space reads, e.g. from Illumina sequencing machines, and color space reads from AB SOLiD machines. Evaluations on both simulated and real data suggest that BWA is ~10–20× faster than MAQ, while achieving similar accuracy. In addition, BWA outputs alignment in the new standard SAM (Sequence Alignment/Map) format. Variant calling and other downstream analyses after the alignment can be achieved with the open source SAMtools software package.
Availability: http://maq.sourceforge.net
Contact: [email protected]
43,862 citations
TL;DR: Bowtie 2 combines the strengths of the full-text minute index with the flexibility and speed of hardware-accelerated dynamic programming algorithms to achieve a combination of high speed, sensitivity and accuracy.
Abstract: As the rate of sequencing increases, greater throughput is demanded from read aligners. The full-text minute index is often used to make alignment very fast and memory-efficient, but the approach is ill-suited to finding longer, gapped alignments. Bowtie 2 combines the strengths of the full-text minute index with the flexibility and speed of hardware-accelerated dynamic programming algorithms to achieve a combination of high speed, sensitivity and accuracy.
37,898 citations
"CARD 2020: antibiotic resistome sur..." refers methods in this paper
...Metagenomics analysis (i.e. RGI bwt) uses Bowtie2 (40) or BWA (41) mapping of sequencing reads to CARD’s PHM reference sequences only, while annotation of genomes or assembly contigs predicts resistome using four of CARD’s AMR detection models: PHM, PVM, RVM and POM (note: RGI currently only scans for nonsynonymous substitutions; not frameshifts, deletions or insertions)....
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...RGI bwt) uses Bowtie2 (40) or BWA (41) mapping of sequencing reads to CARD’s PHM reference sequences only, while annotation of genomes or assembly contigs predicts resistome using four of CARD’s AMR detection models: PHM, PVM, RVM and POM (note: RGI currently only scans for nonsynonymous substitutions; not frameshifts, deletions or insertions)....
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TL;DR: The goals of the PDB are described, the systems in place for data deposition and access, how to obtain further information and plans for the future development of the resource are described.
Abstract: The Protein Data Bank (PDB; http://www.rcsb.org/pdb/ ) is the single worldwide archive of structural data of biological macromolecules. This paper describes the goals of the PDB, the systems in place for data deposition and access, how to obtain further information, and near-term plans for the future development of the resource.
34,239 citations
"CARD 2020: antibiotic resistome sur..." refers methods in this paper
...In 2017, we described the CARD*Shark text-mining algorithm (26) for computer-assisted literature triage, which we have expanded based on the new ARO Drug Class classification tags....
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TL;DR: The new BLAST command-line applications, compared to the current BLAST tools, demonstrate substantial speed improvements for long queries as well as chromosome length database sequences.
Abstract: Sequence similarity searching is a very important bioinformatics task. While Basic Local Alignment Search Tool (BLAST) outperforms exact methods through its use of heuristics, the speed of the current BLAST software is suboptimal for very long queries or database sequences. There are also some shortcomings in the user-interface of the current command-line applications. We describe features and improvements of rewritten BLAST software and introduce new command-line applications. Long query sequences are broken into chunks for processing, in some cases leading to dramatically shorter run times. For long database sequences, it is possible to retrieve only the relevant parts of the sequence, reducing CPU time and memory usage for searches of short queries against databases of contigs or chromosomes. The program can now retrieve masking information for database sequences from the BLAST databases. A new modular software library can now access subject sequence data from arbitrary data sources. We introduce several new features, including strategy files that allow a user to save and reuse their favorite set of options. The strategy files can be uploaded to and downloaded from the NCBI BLAST web site. The new BLAST command-line applications, compared to the current BLAST tools, demonstrate substantial speed improvements for long queries as well as chromosome length database sequences. We have also improved the user interface of the command-line applications.
13,223 citations
"CARD 2020: antibiotic resistome sur..." refers background or methods in this paper
...The website also includes a built-in BLAST instance for comparing sequences to CARD reference sequences and a web instance of RGI for resistome prediction with data visualization tools (https:// card.mcmaster.ca/analyze)....
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...The RVM is functionally similar to the PVM, except it works for rRNA mutations and therefore uses a nucleotide reference sequence and a BLASTN bit score cut-off....
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...Briefly, RGI algorithmically predicts AMR genes and mutations from submitted genomes using a combination of open reading frame prediction with Prodigal (38), sequence alignment with BLAST (35) or DIAMOND (39), and curated resistance mutations included with the AMR detection model....
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...In the same time period, the CARD website hosted ∼45 000 BLAST analyses, ∼220 000 RGI analyses, ∼64 000 data file downloads, and ∼10,000 RGI software downloads....
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...We had determined that the asymptotic nature of the BLAST expectation value (E) gave it very low discriminatory power between different -lactamase gene families (nearly 13 of CARD’s content), but that the linear nature of the BLAST bit score (S′) allowed this level of discrimination....
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