A Bioinformatic Analysis of Integrative Mobile Genetic Elements Highlights Their Role in Bacterial Adaptation

Durrant, Matthew G.; Li, Michelle M.; Siranosian, Benjamin A.; Montgomery, Stephen B.; Bhatt, Ami S.

doi:10.1016/j.chom.2019.10.022

Cited by 150 publications

(110 citation statements)

References 60 publications

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“…Microbiome taxonomic profiling is achieved by culturedependent molecular or phenotypic typing or cultureindependent sequencing of taxonomically informative marker genes or whole metagenomic shotgun sequencing from microbiome samples, within or between individuals [11][12][13][14]. Similarly, features and functions of the microbiome can be assessed by gene-level analysis, metabolomics, and assessment of the abundance of gene pathways for microbial metabolic function [15][16][17][18][19][20]. These analyses are typically conducted in the context of human development throughout life or in connection with clinical outcomes [21].…”

Section: Introductionmentioning

confidence: 99%

Understanding the impact of antibiotic perturbation on the human microbiome

2020

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The human gut microbiome is a dynamic collection of bacteria, archaea, fungi, and viruses that performs essential functions for immune development, pathogen colonization resistance, and food metabolism. Perturbation of the gut microbiome’s ecological balance, commonly by antibiotics, can cause and exacerbate diseases. To predict and successfully rescue such perturbations, first, we must understand the underlying taxonomic and functional dynamics of the microbiome as it changes throughout infancy, childhood, and adulthood. We offer an overview of the healthy gut bacterial architecture over these life stages and comment on vulnerability to short and long courses of antibiotics. Second, the resilience of the microbiome after antibiotic perturbation depends on key characteristics, such as the nature, timing, duration, and spectrum of a course of antibiotics, as well as microbiome modulatory factors such as age, travel, underlying illness, antibiotic resistance pattern, and diet. In this review, we discuss acute and chronic antibiotic perturbations to the microbiome and resistome in the context of microbiome stability and dynamics. We specifically discuss key taxonomic and resistance gene changes that accompany antibiotic treatment of neonates, children, and adults. Restoration of a healthy gut microbial ecosystem after routine antibiotics will require rationally managed exposure to specific antibiotics and microbes. To that end, we review the use of fecal microbiota transplantation and probiotics to direct recolonization of the gut ecosystem. We conclude with our perspectives on how best to assess, predict, and aid recovery of the microbiome after antibiotic perturbation.

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Section: Introductionmentioning

confidence: 99%

Understanding the impact of antibiotic perturbation on the human microbiome

2020

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“…Additionally, computational approaches are evolving in an effort to support more complete and accurate resistome-mobilome colocalization from short-read metagenomic data (Roodgar et al, 2019;Stalder et al, 2019). Finally and most recently, new approaches have been proposed to increase sensitivity of MGE and AMR discovery and classification (Jiang et al, 2019;Durrant et al, 2020). Though we have expressly highlighted the pervasive issue of cargo sequences in MGE databases, a similar problem likely exists in AMR databases as well.…”

Section: Resultsmentioning

confidence: 99%

Mobilization of Antibiotic Resistance: Are Current Approaches for Colocalizing Resistomes and Mobilomes Useful?

et al. 2020

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Slizovskiy et al. Colocalization Analysis of Resistomes-Mobilomes that current alignment-and assembly-based methods estimating resistome mobility yield contradictory and incomplete results, likely constrained by approach-specific data inputs, and bioinformatic limitations. We discuss recent laboratory and computational advancements that may enhance resistome risk analysis in clinical, regulatory, and commercial applications.

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“…Here, this was supported by NCTC13441's repertoire of blaTEM and blaOXY genes, contrasting with EC958's variety of blaCMY ones. This reinforced the view that ST131's accessory resistome is shaped by the environment mediated by plasmids, rather than population structure or geographic factors [126], so perhaps tracking plasmids and MGEs in addition to AMR genes [42,127] could assist treatment diagnostics [128]. By combining seven Clade C genome assemblies, then these with 4,064 Clade C assemblies, we found that most (78%) ST131 had >10 Kb of regions similar to plasmid pEK499 and some (9%) had regions with high similarity to IncI1 plasmid pEK204, suggesting either discrete gains of pEK204-like plasmids in each C subclade or its presence in the Clade C ancestral lineage.…”

Section: Operonmentioning

confidence: 82%

“…Like most AMR genes, these are sandwiched by mobile genetic elements (MGEs) on plasmids and thus can be gained by horizontal gene transfer (HGT) [37][38][39] or lost if not beneficial [40][41]. Of nine common bacterial pathogens, E. coli has the most MGEs, including phageassociated ones and transpose (tnpA) genes [42]. Diverse pathogenic bacteria share MGEs [43][44][45] and HGT may worsen nosocomial outbreaks [46][47][48].…”

Section: Introductionmentioning

confidence: 99%

Plasmids shape the diverse accessory resistomes ofEscherichia coliST131

Decano

Tran

Al-Foori

et al. 2020

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19The human gut microbiome includes beneficial, commensal and pathogenic bacteria that possess 20 antimicrobial resistance (AMR) genes and exchange these predominantly through conjugative 21 plasmids. Escherichia coli is a significant component of the gastrointestinal microbiome and is 22typically non-pathogenic in this niche. In contrast, extra-intestinal pathogenic E. coli (ExPEC) 23including ST131 may occupy other environments like the urinary tract or bloodstream where they 24 express genes enabling AMR and host adhesion like type 1 fimbriae. The extent to which non-25pathogenic gut E. coli and infectious ST131 share AMR genes and key associated plasmids remains 26understudied at a genomic level. Here, we examined AMR gene sharing between gut E. coli and 27 ST131 to discover an extensive shared preterm infant resistome. In addition, individual ST131 show 28 extensive AMR gene diversity highlighting that analyses restricted to the core genome may be limiting 29and could miss AMR gene transfer patterns. We show that pEK499-like segments are ancestral to most 30 ST131 Clade C isolates, contrasting with a minority with substantial pEK204-like regions encoding a 31type IV fimbriae operon. Moreover, ST131 possess extensive diversity at genes encoding type 1, type 32 IV, P and F17-like fimbriae, particular within subclade C2. The type, structure and composition of 33 AMR genes, plasmids and fimbriae varies widely in ST131 and this may mediate pathogenicity and 34 infection outcomes. 35 36

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A Bioinformatic Analysis of Integrative Mobile Genetic Elements Highlights Their Role in Bacterial Adaptation

Abstract: Highlights d Introduces MGEfinder, a bioinformatic toolbox to detect MGE integrations d Describes the MGE repertoire, from small repeats to prophages, of 9 pathogens d MGE insertions affect antibiotic resistance, virulence, pathogenicity across species

Cited by 150 publications

References 60 publications

Understanding the impact of antibiotic perturbation on the human microbiome

Understanding the impact of antibiotic perturbation on the human microbiome

Mobilization of Antibiotic Resistance: Are Current Approaches for Colocalizing Resistomes and Mobilomes Useful?

Plasmids shape the diverse accessory resistomes ofEscherichia coliST131

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