Elucidation of host diversity of the VanD-carrying genomic islands in enterococci and anaerobes

Hashimoto, Yusuke; Hisatsune, Junzo; Suzuki, Masato; Kurushima, Jun; Nomura, Takahiro; Hirakawa, Hidetada; Kojima, Naoko; Ono, Yūichi; Tanimoto, Koichi; Sugai, Motoyuki; Tomita, Haruyoshi

doi:10.1093/jacamr/dlab189

Cited by 5 publications

(7 citation statements)

References 19 publications

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“…A direct repeat sequence of 13 bp (TTCCC[g/a/c]AC[a/g]ATGA) with 11 sites conserved was identified; variations in the 2 variable sites does not correlate with the phylogeny for the ICE (). The findings from this comparative genomic analysis are consistent with previous smaller comparisons [11, 16, 17], and collectively provide strong evidence for a common mobile element for the vanD locus. Phylogenetic trees constructed for both the vanD locus () and the ICE sequences () were highly congruent in their structure, suggesting that both elements are commonly mobilized together.…”

Section: Resultssupporting

confidence: 89%

“…The genes present in this region are suggestive of an integrative conjugative element (ICE). However, the region, while able to be circularized, has not been shown to be mobilizable, and no source for the vanD locus or putative ICE has been conclusively identified [9–11, 13–16, 18, 19], although a recent study has demonstrated that the ICE encompasses genes consistent with those from mobile elements recovered in various anaerobic genera belonging to the order Eubacteriales [17]. The limited number and geographical separation of reported vanD VRE suggest that these isolates have arisen primarily through de novo acquisition of the vanD locus [16].…”

Section: Introductionmentioning

confidence: 99%

“…A few studies have reported on related genomic islands (GIs) associated with the vanD locus [11,16,17]; carried in different genera and divergent lineages of enterococci. The genes present in this region are suggestive of an integrative conjugative element (ICE).…”

Section: Introductionmentioning

confidence: 99%

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Genomic investigation of the emergence of vanD vancomycin-resistant Enterococcus faecium

Baines,

Guérillot,

Ballard

et al. 2023

Access Microbiology

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Vancomycin-resistant Enterococcus (VRE) is an increasingly identified cause of human disease, with most infections resulting from the vanA and vanB genotypes; less is known about other clinically relevant genotypes. Here we report a genomic exploration of a vanD VRE faecium (VREfm), which arose de novo during a single infectious episode. The genomes of the vancomycin-susceptible E. faecium (VSEfm) recipient and resulting VREfm were subjected to long-read sequencing and closed, with whole-genome alignments, cross-mapping and orthologue clustering used to identify genomic variation. Three key differences were identified. (i) The VREfm chromosome gained a 142.6 kb integrative conjugative element (ICE) harbouring the vanD locus. (ii) The native ligase (ddl) was disrupted by an ISEfm1 insertion. (iii) A large 1.74 Mb chromosomal inversion of unknown consequence occurred. Alignment and phylogenetic-based comparisons of the VREfm with a global collection of vanD-harbouring genomes identified strong similarities in the 120–160 kb genomic region surrounding vanD, suggestive of a common mobile element and integration site, irrespective of the diverse taxonomic, geographical and host origins of the isolates. This isolate diversity revealed that this putative ICE (and its source) is globally disseminated and is capable of being acquired by different genera. Although the incidence of vanD VREfm is low, understanding its emergence and potential for spread is crucial for the ongoing efforts to reduce antimicrobial resistance.

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Section: Resultssupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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Genomic investigation of the emergence of vanD vancomycin-resistant Enterococcus faecium

Baines,

Guérillot,

Ballard

et al. 2023

Access Microbiology

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“…Novel observations include the linkage of the vancomycin resistance genes vanHDX to the genus Eubacterium in the Y_3C_B dataset. This gene has not been observed in Eubacterium previously, although vanD has been found in several other Eubacteriales, including Ruminococcus and Blautia [75, 76]. Notably, VanD-type glycopeptide resistance genes in gut commensals can be transferred to the opportunistic pathogen Enterococcus faecium , complicating therapy of infections caused by this species [77].…”

Section: Discussionmentioning

confidence: 99%

Noise reduction strategies in metagenomic chromosome confirmation capture to link antibiotic resistance genes to microbial hosts

et al. 2023

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The gut microbiota is a reservoir for antimicrobial resistance genes (ARGs). With current sequencing methods, it is difficult to assign ARGs to their microbial hosts, particularly if these ARGs are located on plasmids. Metagenomic chromosome conformation capture approaches (meta3C and Hi-C) have recently been developed to link bacterial genes to phylogenetic markers, thus potentially allowing the assignment of ARGs to their hosts on a microbiome-wide scale. Here, we generated a meta3C dataset of a human stool sample and used previously published meta3C and Hi-C datasets to investigate bacterial hosts of ARGs in the human gut microbiome. Sequence reads mapping to repetitive elements were found to cause problematic noise in, and may importantly skew interpretation of, meta3C and Hi-C data. We provide a strategy to improve the signal-to-noise ratio by discarding reads that map to insertion sequence elements and to the end of contigs. We also show the importance of using spike-in controls to quantify whether the cross-linking step in meta3C and Hi-C protocols has been successful. After filtering to remove artefactual links, 87 ARGs were assigned to their bacterial hosts across all datasets, including 27 ARGs in the meta3C dataset we generated. We show that commensal gut bacteria are an important reservoir for ARGs, with genes coding for aminoglycoside and tetracycline resistance being widespread in anaerobic commensals of the human gut.

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“…Novel observations include the linkage of the vancomycin resistance genes vanHDX to the genus Eubacterium in the Y_3C_B dataset. This gene has not been observed in Eubacterium previously, although vanD has been found in several other Eubacteriales, including Ruminococcus and Blautia [55,56]. Notably, VanD-type glycopeptide resistance genes in gut commensals can be transferred to the opportunistic pathogen E. faecium , complicating therapy of infections caused by this species [57].…”

Section: Discussionmentioning

confidence: 99%

Noise reduction strategies in metagenomic chromosome confirmation capture to link antibiotic resistance genes to microbial hosts

McCallum

Rossiter

Quraishi

et al. 2022

Preprint

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The gut microbiota is a reservoir for antimicrobial resistance genes (ARGs). With current sequencing methods, it is difficult to assign ARGs to their microbial hosts, particularly if these ARGs are located on plasmids. Metagenomic chromosome conformation capture approaches (meta3C and Hi-C), have recently been developed to link bacterial genes to phylogenetic markers, thus potentially allowing the assignment of ARGs to their hosts on a microbiome-wide scale. Here, we generated a meta3C dataset of a human stool sample and used previously published meta3C and Hi-C datasets to investigate bacterial hosts of ARGs in the human gut microbiome. Sequence reads mapping to repetitive elements were found to cause problematic noise in, and may importantly skew interpretation of, meta3C and Hi-C data. We provide a strategy to improve the signal-to-noise ratio by discarding reads that map to repetitive elements and to the end of contigs. We also show the importance of using spike-in controls to quantify whether the cross-linking step in meta3C and Hi-C protocols has been successful. After filtering for spurious links, 87 ARGs were linked to their bacterial hosts across all datasets, including 27 ARGs in the meta3C dataset we generated. We show that commensal gut bacteria are an important reservoir for ARGs, with genes encoding for aminoglycoside and tetracycline resistance being widespread in anaerobic commensals of the human gut.

show abstract

Elucidation of host diversity of the VanD-carrying genomic islands in enterococci and anaerobes

Cited by 5 publications

References 19 publications

Genomic investigation of the emergence of vanD vancomycin-resistant Enterococcus faecium

Genomic investigation of the emergence of vanD vancomycin-resistant Enterococcus faecium

Noise reduction strategies in metagenomic chromosome confirmation capture to link antibiotic resistance genes to microbial hosts

Noise reduction strategies in metagenomic chromosome confirmation capture to link antibiotic resistance genes to microbial hosts

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