Global genomic epidemiology of bla GES-5 carbapenemase-associated integrons DOI Creative Commons
William Matlock,

Liam P. Shaw,

Nicole Stoesser

et al.

Microbial Genomics, Journal Year: 2024, Volume and Issue: 10(12)

Published: Dec. 4, 2024

Antimicrobial resistance (AMR) gene cassettes comprise an AMR flanked by short recombination sites ( attI and attC or ). Integrons are genetic elements able to capture, excise shuffle these cassettes, providing ‘adaptation on demand’, can be found both chromosomes plasmids. Understanding the patterns of integron diversity may help understand epidemiology genes. As a case study, we examined clinical bla GES-5 , integron-associated class A carbapenemase first reported in Greece 2004 since observed worldwide, which our knowledge has not been subject previous global analysis. Using dataset comprising all de-duplicated NCBI contigs containing n =104), developed pangenome graph-based workflow characterize cluster -associated integrons. We demonstrate that integrons plasmids different those chromosomes. Chromosomal were almost identified Pseudomonas aeruginosa ST235, with consistent cassette content order. instances where insertion sequence IS 110 disrupted sites, might immobilize explain conserved structure despite presence intI1 integrase promoters, would typically facilitate capture excision rearrangement. The plasmid-associated more diverse their order, could indication greater activity ‘shuffling’

Language: Английский

ODGI: understanding pangenome graphs DOI Creative Commons
Andrea Guarracino, Simon Heumos, Sven Nahnsen

et al.

Bioinformatics, Journal Year: 2022, Volume and Issue: 38(13), P. 3319 - 3326

Published: May 10, 2022

Pangenome graphs provide a complete representation of the mutual alignment collections genomes. These models offer opportunity to study entire genomic diversity population, including structurally complex regions. Nevertheless, analyzing hundreds gigabase-scale genomes using pangenome is difficult as it not well-supported by existing tools. Hence, fast and versatile software required ask advanced questions such data in an efficient way.

Language: Английский

Citations

97
Building pangenome graphs DOI
Erik Garrison, Andrea Guarracino, Simon Heumos

et al.

Nature Methods, Journal Year: 2024, Volume and Issue: 21(11), P. 2008 - 2012

Published: Oct. 21, 2024

Language: Английский

Citations

35
Enterobacterales plasmid sharing amongst human bloodstream infections, livestock, wastewater, and waterway niches in Oxfordshire, UK DOI Creative Commons
William Matlock, Samuel Lipworth, Kevin Chau

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: March 23, 2023

Plasmids enable the dissemination of antimicrobial resistance (AMR) in common Enterobacterales pathogens, representing a major public health challenge. However, extent plasmid sharing and evolution between causing human infections other niches remains unclear, including emergence plasmids. Dense, unselected sampling is essential to developing our understanding epidemiology designing appropriate interventions limit plasmid-associated AMR. We established geographically temporally restricted collection bloodstream infection (BSI)-associated, livestock-associated (cattle, pig, poultry, sheep faeces, farm soils) wastewater treatment work (WwTW)-associated (influent, effluent, waterways upstream/downstream effluent outlets) Enterobacterales. Isolates were collected 2008 2020 from sites <60 km apart Oxfordshire, UK. Pangenome analysis clusters revealed shared 'backbones', with phylogenies suggesting an intertwined ecology where well-conserved backbones carry diverse accessory functions, AMR genes. Many 'backbones' seen across species niches, raising possibility that movement these followed by rapid gene change could be relatively common. Overall, signature identical likely highly transient one, implying might occurring at greater rates than previously estimated, challenge for future genomic One Health studies.

Language: Английский

Citations

14
TheMycobacterium tuberculosiscomplex pangenome is small and driven by sub-lineage-specific regions of difference DOI Creative Commons
Mahboobeh Behruznia, Maximillian G. Marin, Maha Farhat

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 14, 2024

Abstract The Mycobacterium tuberculosis complex (MTBC) is a group of bacteria causing (TB) in humans and animals. Understanding MTBC genetic diversity crucial for insights into its adaptation traits related to survival, virulence, antibiotic resistance. While it known that within characterised by large lineage-specific deletions (regions difference [RD]), comprehensive pangenomic analysis incorporating both coding non-coding regions remains unexplored. We utilised curated dataset representing various genomes, including under-represented lineages quantify the true pangenome. was found have small, closed pangenome with distinct genomic features RDs between (as previously known) sub-lineages. accessory genome identified be product reduction, showing independent deletions. This variation has implications like drug resistance, metabolism. study provides understanding pangenome, highlighting importance reduction evolution within-lineage content present. findings underline significance variations determining pathogenic different lineages.

Language: Английский

Citations

2
TALCO: Tiling Genome Sequence Alignment Using Convergence of Traceback Pointers DOI

Sumit Walia,

Cheng Ye,

Arkid Bera

et al.

Published: March 2, 2024

Pairwise sequence alignment is one of the most fundamental and computationally intensive steps in genome analysis. With improving costs throughput third-generation sequencing technologies growing availability whole-genome datasets, longer alignments are becoming more common field bioinformatics. However, high memory demands long create significant obstacles to hardware acceleration. Banding techniques allow recovering high-quality with lower memory, but they also require for than what typically available on-chip accelerators. Recently, tiling-based accelerators have made remarkable strides accelerating alignment, achieving three four orders magnitude improvement over software tools without any restrictions on length. it crucial note that existing tiling heuristics can cause quality degrade, which a critical concern wider adoption To address this issue, paper describes TALCO - novel method alignments, that, similar prior techniques, maintains constant footprint during acceleration step independent unlike previous ensures optimal under banding constraints. does by leveraging convergence traceback paths beyond tile single point boundary strategy generalizes well broad set algorithms. We demonstrate advantages applying two different widely-used banded algorithms, X-Drop WFA-Adapt. best our knowledge, first time technique being applied non-classical algorithm such as The beneficial both hardware. When implemented software, reduces requirements WFA-Adapt algorithms up 39 × 57 ×, respectively, when ASIC accelerator, provides 1,900 2,000 throughput/watt CPU baselines implementing same Compared state-of-the-art GPU heuristics, 50 1.1 throughput, while maintaining higher quality. Code availability: https://github.com/TurakhiaLab/TALCO.

Language: Английский

Citations

2
The Evolution of Extreme Genetic Variability in a Parasite-Resistance Complex DOI Creative Commons
Suha Naser-Khdour,

Fabian Scheuber,

Peter D. Fields

et al.

Genome Biology and Evolution, Journal Year: 2024, Volume and Issue: 16(10)

Published: Oct. 1, 2024

Genomic regions that play a role in parasite defense are often found to be highly variable, with the major histocompatibility complex serving as an iconic example. Single nucleotide polymorphisms may represent only small portion of this variability, Indel and copy number variation further contributing. In extreme cases, haplotypes no longer recognized orthologous. Understanding evolution such divergent is challenging because most not visible using reference-assisted genomic approaches. Here we analyze case Pasteuria Resistance Complex crustacean Daphnia magna, host against common virulent bacterium ramosa. Two region have been previously described, parts it being nonhomologous, has shown under balancing selection. Using pan-genome analysis tree reconciliation methods explore its characteristics within between species other Cladoceran species, our revealed remarkable diversity even among many nonhomologous hyper-divergent haplotypes. The characterized by extensive duplication losses Fucosyltransferase (FuT) Galactosyltransferase (GalT) genes believed defense. can traced back ancestors over 250 million years. unique combination ancient resistance dynamic, environment presents fascinating opportunity investigate long-term maintenance polymorphisms. Our findings offer valuable insights into evolutionary forces shaping disease adaptation, genus Daphnia, but potentially across entire Cladocera class.

Language: Английский

Citations

1
Visualizing and quantifying structural diversity around mobile resistance genes DOI Creative Commons
Liam P. Shaw, Richard A. Neher

Microbial Genomics, Journal Year: 2023, Volume and Issue: 9(12)

Published: Dec. 20, 2023

Understanding the evolution of mobile genes is important for understanding spread antimicrobial resistance (AMR). Many clinically AMR have been mobilized by genetic elements (MGEs) on kilobase scale, such as integrons and transposons, which can integrate into both chromosomes plasmids lead to rapid gene through bacterial populations. Looking at flanking regions these in diverse genomes highlight common structures reveal patterns MGE spread. However, historically this has a largely descriptive process, relying annotation expert knowledge. Here we describe general method visualize quantify structural diversity around using pangraph find blocks homologous sequence. We apply set 12 beta-lactamase provide interactive visualizations their https://liampshaw.github.io/flanking-regions. show that nucleotide-level variation itself generally correlates with increased its regions, demonstrating relationship between rates mutational evolution, bias greater upstream. Our framework starting point investigate rules horizontal new

Language: Английский

Citations

3
Visualizing and quantifying structural diversity around mobile resistance genes DOI Creative Commons
Liam P. Shaw, Richard A. Neher

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 7, 2023

Abstract Understanding the evolution of mobile genes is important for understanding spread antimicrobial resistance (AMR). Many clinically AMR have been mobilized by genetic elements (MGEs) on kilobase scale, such as integrons and transposons, which can integrate into both chromosomes plasmids lead to rapid gene through bacterial populations. Looking at flanking regions these in diverse genomes highlight common structures reveal patterns MGE spread. However, historically this has a largely descriptive process, relying annotation expert knowledge. Here we describe general method visualize quantify structural diversity around using pangraph find blocks homologous sequence. We apply set twelve beta-lactamase provide interactive visualizations their https://liampshaw.github.io/flanking-regions . show that nucleotide-level variation itself generally correlates with increased its regions, demonstrating relationship between rates mutational evolution, bias greater upstream. Our framework starting point investigate rules horizontal new Impact statement challenging because high variability genomic contexts. outline fast computational approach identifies stretches sequence gene, simultaneously producing quantifying within them. As an example, genes. correlated mutations it there upstream many There may be other about recovered kind analysis.

Language: Английский

Citations

2
Global genomic epidemiology ofblaGES-5carbapenemase-associated integrons DOI Creative Commons
William Matlock, Liam P. Shaw, Nicole Stoesser

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 10, 2024

Abstract Antimicrobial resistance (AMR) gene cassettes comprise an AMR flanked by short recombination sites ( attI × attC or ). Integrons are genetic elements able to capture, excise, and shuffle these cassettes, providing ‘adaptation on demand’, can be found both chromosomes plasmids. Understanding the patterns of integron diversity may help understand epidemiology genes. As a case study, we examined clinical bla GES-5 , integron-associated class A carbapenemase first reported in Greece 2004 since observed worldwide, which our knowledge has not been subject previous global analysis. Using dataset comprising all NCBI contigs containing n = 431), developed pangenome graph-based workflow characterise cluster -associated integrons. We demonstrate that integrons plasmids different those chromosomes. Chromosomal were almost identified P. aeruginosa ST235, with consistent cassette content order. instances where insertion sequence IS 110 disrupted sites, might immobilise explain conserved structure despite presence intI1 integrase promoters, would typically facilitate capture excision rearrangement. The plasmid-associated more diverse their order, could indication greater activity ‘shuffling’

Language: Английский

Citations

0
Global dissemination of npmA mediated pan-aminoglycoside resistance via a novel mobile genetic element in Gram-positive bacteria DOI Creative Commons
Bruno González‐Zorn, Carlos Serna,

Bosco R. Matamoros

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: May 16, 2024

Abstract The npmA gene, encoding a 16S rRNA methyltransferase, confers resistance to all clinically available aminoglycosides, posing significant threat effective antibiotic therapy. Here, we investigated the distribution and mobilization mechanisms of variants, npmA1 npmA2, through an exhaustive analysis 692,646 bacterial genomes. We identified worldwide dissemination npmA2 in Clostridioides difficile, predominantly carried by C. difficile ST11. also detected two vancomycin-resistant Enterococcus faecium isolates from Dutch hospital. Upon sequencing phenotypic analysis, determined that E. were pan-resistant aminoglycosides. Genomic characterization linked novel composite transposon Tn7734 which, turn, is integrated within previously uncharacterized Integrative Conjugative Element (ICE) Tn7740, present both npmA2-carrying clinical isolates. These findings suggest role ICE Tn7740 enabling cross-species gene between these gram-positive bacteria emphasize risk mobile genetic elements transferring pan-aminoglycoside important pathogens.

Language: Английский

Citations

0