scholarly journals Mobile genetic element insertions drive antibiotic resistance across pathogens

2019 ◽  
Author(s):  
Matthew G. Durrant ◽  
Michelle M. Li ◽  
Ben Siranosian ◽  
Ami S. Bhatt
Keyword(s):  
Antibiotic Resistance ◽  
De Novo ◽  
Bacterial Species ◽  
Mobile Element ◽  
Mobile Genetic Elements ◽  
Mobile Elements ◽  
Genetic Elements ◽  
Element Insertion ◽  
A Genome ◽  
Mobile Element Insertion

AbstractMobile genetic elements contribute to bacterial adaptation and evolution; however, detecting these elements in a high-throughput and unbiased manner remains challenging. Here, we demonstrate ade novoapproach to identify mobile elements from short-read sequencing data. The method identifies the precise site of mobile element insertion and infers the identity of the inserted sequence. This is an improvement over previous methods that either rely on curated databases of known mobile elements or rely on ‘split-read’ alignments that assume the inserted element exists within the reference genome. We apply our approach to 12,419 sequenced isolates of nine prevalent bacterial pathogens, and we identify hundreds of known and novel mobile genetic elements, including many candidate insertion sequences. We find that the mobile element repertoire and insertion rate vary considerably across species, and that many of the identified mobile elements are biased toward certain target sequences, several of them being highly specific. Mobile element insertion hotspots often cluster near genes involved in mechanisms of antibiotic resistance, and such insertions are associated with antibiotic resistance in laboratory experiments and clinical isolates. Finally, we demonstrate that mutagenesis caused by these mobile elements contributes to antibiotic resistance in a genome-wide association study of mobile element insertions in pathogenicEscherichia coli. In summary, by applying ade novoapproach to precisely identify mobile genetic elements and their insertion sites, we thoroughly characterize the mobile element repertoire and insertion spectrum of nine pathogenic bacterial species and find that mobile element insertions play a significant role in the evolution of clinically relevant phenotypes, such as antibiotic resistance.

scholarly journals Toolbox for Mobile-Element Insertion Detection on Cancer Genomes

2015 ◽  
Vol 14s1 ◽  
pp. CIN.S24657
Author(s):  
Wan-Ping Lee ◽  
Jiantao Wu ◽  
Gabor T. Marth
Keyword(s):  
Human Genome ◽  
Mobile Element ◽  
Mobile Elements ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Next Generation Sequencing Data ◽  
Sequencing Data ◽  
Element Insertion ◽  
Human Genome Evolution ◽  
Mobile Element Insertion

Mobile elements constitute greater than 45% of the human genome as a result of repeated insertion events during human genome evolution. Although most of mobile elements are fixed within the human population, some elements (including ALU, long interspersed elements (LINE) 1 (L1), and SVA) are still actively duplicating and may result in life-threatening human diseases such as cancer, motivating the need for accurate mobile-element insertion (MEI) detection tools. We developed a software package, TANGRAM, for MEI detection in next-generation sequencing data, currently serving as the primary MEI detection tool in the 1000 Genomes Project. TANGRAM takes advantage of valuable mapping information provided by our own MOSAIK mapper, and until recently required MOSAIK mappings as its input. In this study, we report a new feature that enables TANGRAM to be used on alignments generated by any mainstream short-read mapper, making it accessible for many genomic users. To demonstrate its utility for cancer genome analysis, we have applied TANGRAM to the TCGA (The Cancer Genome Atlas) mutation calling benchmark 4 dataset. TANGRAM is fast, accurate, easy to use, and open source on https://github.com/jiantao/Tangram .

scholarly journals Toolbox for Mobile-Element Insertion Detection on Cancer Genomes

2014 ◽  
Vol 13s4 ◽  
pp. CIN.S13979 ◽  
Author(s):  
Wan-Ping Lee ◽  
Jiantao Wu ◽  
Gabor T. Marth
Keyword(s):  
Human Genome ◽  
Mobile Element ◽  
Mobile Elements ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Next Generation Sequencing Data ◽  
Sequencing Data ◽  
Element Insertion ◽  
Human Genome Evolution ◽  
Mobile Element Insertion

Mobile elements constitute greater than 45% of the human genome as a result of repeated insertion events during human genome evolution. Although most of mobile elements are fixed within the human population, some elements (including ALU, long interspersed elements (LINE) 1 (L1), and SVA) are still actively duplicating and may result in life-threatening human diseases such as cancer, motivating the need for accurate mobile-element insertion (MEI) detection tools. We developed a software package, TANGRAM, for MEI detection in next-generation sequencing data, currently serving as the primary MEI detection tool in the 1000 Genomes Project. TANGRAM takes advantage of valuable mapping information provided by our own MOSAIK mapper, and until recently required MOSAIK mappings as its input. In this study, we report a new feature that enables TANGRAM to be used on alignments generated by any mainstream short-read mapper, making it accessible for many genomic users. To demonstrate its utility for cancer genome analysis, we have applied TANGRAM to the TCGA (The Cancer Genome Atlas) mutation calling benchmark 4 dataset. TANGRAM is fast, accurate, easy to use, and open source on https://github.com/jiantao/Tangram .

Genome-based characterization of a plasmid-associated micrococcin P1 biosynthetic gene cluster and virulence factors in Mammaliicoccus sciuri IMDO-S72

2021 ◽  
Author(s):  
David Van der Veken ◽  
Charlie Hollanders ◽  
Marko Verce ◽  
Chris Michiels ◽  
Steven Ballet ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Gene Cluster ◽  
Virulence Factors ◽  
Resistance Genes ◽  
De Novo ◽  
Antibiotic Resistance Genes ◽  
Mobile Genetic Elements ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Genetic Elements

Analysis of the de novo assembled genome of Mammaliicoccus sciuri IMDO-S72 revealed the genetically encoded machinery behind its earlier reported antibacterial phenotype and gave further insight into the repertoire of putative virulence factors of this recently reclassified species. A plasmid-encoded biosynthetic gene cluster was held responsible for the antimicrobial activity of M. sciuri IMDO-S72, comprising genes involved in thiopeptide production. The compound encoded by this gene cluster was structurally identified as micrococcin P1. Further examination of its genome highlighted the ubiquitous presence of innate virulence factors mainly involved in surface colonization. Determinants contributing to aggressive virulence were generally absent, with exception of a plasmid-associated ica cluster. The native antibiotic resistance genes sal (A) and mecA were detected within the genome, amongst others, but were not consistently linked with a resistant phenotype. While mobile genetic elements were identified within the genome, such as an untypeable SCC element, they proved to be generally free of virulence- and antibiotic-related genes. These results further suggest a commensal lifestyle of M. sciuri and indicate the association of antibiotic resistance determinants with mobile genetic elements, as an important factor in conferring antibiotic resistance, in addition to their unilateral annotation. Importance Mammaliicoccus sciuri has been put forward as an important carrier of virulence and antibiotic resistance genes, which can be transmitted to clinically important staphylococcal species such as Staphylococcus aureus . As a common inhabitant of mammal skin, this species is believed to have a predominant commensal lifestyle although it has been reported as an opportunistic pathogen in some cases. This study provides an extensive genome-wide description of its putative virulence potential taking into consideration the genomic context in which these genes appear, an aspect that is often overlooked during virulence analysis. Additional genome and biochemical analysis linked M. sciuri with the production of micrococcin P1, gaining further insight to which extent these biosynthetic gene cluster are distributed amongst different related species. The frequent plasmid-associated character hints that these traits can be horizontally transferred and might confer a competitive advantage to its recipient within its ecological niche.

scholarly journals Genetic diversity, mobilisation and spread of the yersiniabactin-encoding mobile element ICEKp inKlebsiella pneumoniaepopulations

2017 ◽  
Author(s):  
Margaret M. C. Lam ◽  
Ryan R. Wick ◽  
Kelly L. Wyres ◽  
Claire L. Gorrie ◽  
Louise M. Judd ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Population Genomics ◽  
Bacterial Species ◽  
Critical Role ◽  
Mobile Element ◽  
Mobile Genetic Elements ◽  
Virulence Determinants ◽  
Genome Sequences ◽  
Genetic Elements ◽  
Resistant Strains

ABSTRACTMobile genetic elements (MGEs) that frequently transfer within and between bacterial species play a critical role in bacterial evolution, and often carry key accessory genes that associate with a bacteria’s ability to cause disease. MGEs carrying antimicrobial resistance (AMR) and/or virulence determinants are common in opportunistic pathogenKlebsiella pneumoniae, which are a leading cause of highly drug-resistant infections in hospitals. Well-characterised virulence determinants inK. pneumoniaeinclude the polyketide synthesis lociybtandclb(also known aspks), encoding the iron-scavenging siderophore yersiniabactin and genotoxin colibactin respectively. These loci are located within an MGE called ICEKp, which is the most common virulence-associated MGE ofK. pneumoniae,providing a mechanism for these virulence factors to spread within the population.Here we apply population genomics to investigate the prevalence, evolution and mobility ofybtandclbinK. pneumoniaepopulations through comparative analysis of 2,498 whole genome sequences. Theybtlocus was detected in 40% ofK. pneumoniaegenomes, particularly amongst those associated with invasive infections. We identified 17 distinctybtlineages and 3clblineages, each associated with one of 14 different structural variants of ICEKp. Comparison with the wider Enterobacteriaceae population showed occasional ICEKpacquisition by other members. Theclblocus was present in 14% of allK. pneumoniaeand 38.4% ofybt+ genomes. Hundreds of independent ICEKpintegration events were detected affecting hundreds of phylogenetically distinctK. pneumoniaelineages, including ≥19 in the globally-disseminated carbapenem-resistant clone CG258. A novel plasmid-encoded form ofybtwas also identified, representing a new mechanism forybtdispersal inK. pneumoniaepopulations. These data show that MGEs carryingybtandclbcirculate freely in theK. pneumoniaepopulation, including among multidrug-resistant strains, and should be considered a target for genomic surveillance along with AMR determinants.AUTHOR SUMMARYKlebsiella pneumoniaeinfections are becoming increasingly difficult to treat with antibiotics. SomeK. pneumoniaestrains also carry extra genes that allow them to synthesise yersiniabactin, an iron-scavenging molecule, which enhances their ability to cause disease. These genes are located on a genetic element that can easily transfer between strains. Here, we screened 2498K. pneumoniaegenome sequences and found substantial diversity in the yersiniabactin genes and the associated genetic elements, including a novel mechanism of transfer, and detected hundreds of distinct yersiniabactin acquisition events betweenK. pneumoniaestrains. We show that these yersiniabactin mobile genetic elements are specifically adapted to theK. pneumoniaepopulation but also occasionally acquired by other bacterial members belonging to the Enterobacteriaceae family such asE. coli.These insights into the movement and genetics of yersiniabactin genes allow tracking of the evolution and spread of yersiniabactin in globalK. pneumoniaepopulations and monitoring for acquisition of yersiniabactin in antibiotic-resistant strains.

scholarly journals Black Queen Evolution and Trophic Interactions Determine Plasmid Survival after the Disruption of the Conjugation Network

mSystems ◽  
2018 ◽  
Vol 3 (5) ◽  
Author(s):  
Johannes Cairns ◽  
Katariina Koskinen ◽  
Reetta Penttinen ◽  
Tommi Patinen ◽  
Anna Hartikainen ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Communities ◽  
Resistance Mechanism ◽  
Real Life ◽  
Ecological Factors ◽  
Mobile Genetic Elements ◽  
Resistance Mechanisms ◽  
Antibiotics Resistance ◽  
Bacterial Populations ◽  
Genetic Elements

ABSTRACTMobile genetic elements such as conjugative plasmids are responsible for antibiotic resistance phenotypes in many bacterial pathogens. The ability to conjugate, the presence of antibiotics, and ecological interactions all have a notable role in the persistence of plasmids in bacterial populations. Here, we set out to investigate the contribution of these factors when the conjugation network was disturbed by a plasmid-dependent bacteriophage. Phage alone effectively caused the population to lose plasmids, thus rendering them susceptible to antibiotics. Leakiness of the antibiotic resistance mechanism allowing Black Queen evolution (i.e. a “race to the bottom”) was a more significant factor than the antibiotic concentration (lethal vs sublethal) in determining plasmid prevalence. Interestingly, plasmid loss was also prevented by protozoan predation. These results show that outcomes of attempts to resensitize bacterial communities by disrupting the conjugation network are highly dependent on ecological factors and resistance mechanisms.IMPORTANCEBacterial antibiotic resistance is often a part of mobile genetic elements that move from one bacterium to another. By interfering with the horizontal movement and the maintenance of these elements, it is possible to remove the resistance from the population. Here, we show that a so-called plasmid-dependent bacteriophage causes the initially resistant bacterial population to become susceptible to antibiotics. However, this effect is efficiently countered when the system also contains a predator that feeds on bacteria. Moreover, when the environment contains antibiotics, the survival of resistance is dependent on the resistance mechanism. When bacteria can help their contemporaries to degrade antibiotics, resistance is maintained by only a fraction of the community. On the other hand, when bacteria cannot help others, then all bacteria remain resistant. The concentration of the antibiotic played a less notable role than the antibiotic used. This report shows that the survival of antibiotic resistance in bacterial communities represents a complex process where many factors present in real-life systems define whether or not resistance is actually lost.

scholarly journals Transmission of ESBL-producing Enterobacteriaceae and their mobile genetic elements—identification of sources by whole genome sequencing: study protocol for an observational study in Switzerland

BMJ Open ◽  
2018 ◽  
Vol 8 (2) ◽  
pp. e021823 ◽  
Author(s):  
Tanja Stadler ◽  
Dominik Meinel ◽  
Lisandra Aguilar-Bultet ◽  
Jana S Huisman ◽  
Ruth Schindler ◽  
...  
Keyword(s):  
Observational Study ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Bacterial Species ◽  
Mobile Genetic Elements ◽  
University Hospital ◽  
Whole Genome ◽  
Hospital Acquired Infections ◽  
Genetic Elements ◽  
Hospital Acquired

IntroductionExtended-spectrum beta-lactamases (ESBL)-producing Enterobacteriaceae were first described in relation with hospital-acquired infections. In the 2000s, the epidemiology of ESBL-producing organisms changed as especially ESBL-producingEscherichia coliwas increasingly described as an important cause of community-acquired infections, supporting the hypothesis that in more recent years ESBL-producing Enterobacteriaceae have probably been imported into hospitals rather than vice versa. Transmission of ESBL-producing Enterobacteriaceae is complicated by ESBL genes being encoded on self-transmissible plasmids, which can be exchanged among the same and different bacterial species. The aim of this research project is to quantify hospital-wide transmission of ESBL-producing Enterobacteriaceae on both the level of bacterial species and the mobile genetic elements and to determine if hospital-acquired infections caused by ESBL producers are related to strains and mobile genetic elements predominantly circulating in the community or in the healthcare setting. This distinction is critical in prevention since the former emphasises the urgent need to establish or reinforce antibiotic stewardship programmes, and the latter would call for more rigorous infection control.Methods and analysisThis protocol presents an observational study that will be performed at the University Hospital Basel and in the city of Basel, Switzerland. ESBL-producing Enterobacteriaceae will be collected from any specimens obtained by routine clinical practice or by active screening in both inpatient and outpatient settings, as well as from wastewater samples and foodstuffs, both collected monthly over a 12-month period for analyses by whole genome sequencing. Bacterial chromosomal, plasmid and ESBL-gene sequences will be compared within the cohort to determine genetic relatedness and migration between humans and their environment.Ethics and disseminationThis study has been approved by the local ethics committee (Ethikkommission Nordwest-und Zentralschweiz) as a quality control project (Project-ID 2017–00100). The results of this study will be published in peer-reviewed medical journals, communicated to participants, the general public and all relevant stakeholders.

scholarly journals A Novel and Direct Metamobilome Approach improves the Detection of Larger-sized Circular Elements across Kingdoms

2019 ◽  
Author(s):  
Katrine Skov Alanin ◽  
Tue Sparholt Jørgensen ◽  
Patrick Browne ◽  
Bent Petersen ◽  
Leise Riber ◽  
...  
Keyword(s):  
Multiple Displacement Amplification ◽  
Bacterial Species ◽  
Human Health Risk ◽  
Prokaryotic Genome ◽  
Mobile Genetic Elements ◽  
Wastewater Sample ◽  
Mobile Dna ◽  
Complex Samples ◽  
Genetic Elements ◽  
Dna Elements

AbstractMobile genetic elements (MGEs) are instrumental in natural prokaryotic genome editing, permitting genome plasticity and allowing microbes to accumulate immense genetic diversity. MGEs include DNA elements such as plasmids, transposons and Insertion Sequences (IS-elements), as well as bacteriophages (phages), and they serve as a vast communal gene pool. These mobile DNA elements represent a human health risk as they can add new traits, such as antibiotic resistance or virulence, to a bacterial strain. Sequencing libraries targeting circular MGEs, referred to as mobilomes, allows the expansion of our current understanding of the mechanisms behind the mobility, prevalence and content of these elements. However, metamobilomes from bacterial communities are not studied to the same extent as metagenomics, partly because of methodological biases arising from multiple displacement amplification (MDA), often used in previous metamobilome publications. In this study, we show that MDA is detrimental to the detection of larger-sized plasmids if small plasmids are present by comparing the abundances of reads mapping to plasmids in a wastewater sample spiked with a mock community of selected plasmids with and without MDA. Furthermore, we show that it is possible to produce samples consisting almost exclusively of circular MGEs and obtain a catalog of larger, complete, circular MGEs from complex samples without the use of MDA.ImportanceMobile genetic elements (MGEs) can transport genetic information between genomes in different bacterial species, adding new traits, potentially generating dangerous multidrug-resistant pathogens. In fact, plasmids and circular MGEs can encode bacterial genetic specializations such as virulence, resistance to metals, antimicrobial compounds, and bacteriophages, as well as the degradation of xenobiotics. For this reason, circular MGEs are crucial to investigate, but they are often missed in metagenomics and ecological studies. In this study, we present, for the first time, an improved method, which reduces the bias towards small MGEs and we demonstrate that this method can unveil larger, complete circular MGEs from complex samples without the use of multiple displacement amplification. This method may result in the detection of larger-sized plasmids that have hitherto remained unnoticed and therefore has the potential to reveal novel accessory genes, acting as possible targets in the development of preventive strategies directed at pathogens.

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