scholarly journals The Comprehensive Antibiotic Resistance Database

2013 ◽  
Vol 57 (7) ◽  
pp. 3348-3357 ◽  
Author(s):  
Andrew G. McArthur ◽  
Nicholas Waglechner ◽  
Fazmin Nizam ◽  
Austin Yan ◽  
Marisa A. Azad ◽  
...  

ABSTRACTThe field of antibiotic drug discovery and the monitoring of new antibiotic resistance elements have yet to fully exploit the power of the genome revolution. Despite the fact that the first genomes sequenced of free living organisms were those of bacteria, there have been few specialized bioinformatic tools developed to mine the growing amount of genomic data associated with pathogens. In particular, there are few tools to study the genetics and genomics of antibiotic resistance and how it impacts bacterial populations, ecology, and the clinic. We have initiated development of such tools in the form of the Comprehensive Antibiotic Research Database (CARD;http://arpcard.mcmaster.ca). The CARD integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in new unannotated genome sequences. This unique platform provides an informatic tool that bridges antibiotic resistance concerns in health care, agriculture, and the environment.

2017 ◽  
Author(s):  
Alfonso Santos-Lopez ◽  
Cristina Bernabe-Balas ◽  
Alvaro San Millan ◽  
Rafael Ortega-Huedo ◽  
Andreas Hoefer ◽  
...  

AbstractThe coexistence of multicopy plasmids is a common phenomenon. However, the evolutionary forces promoting these genotypes are poorly understood. In this study, we have analyzed multiple ColE1 plasmids (pB1000, pB1005 and pB1006) coexisting within Haemophilus influenzae RdKW20 in all possible combinations. When transformed into the naïve host, each plasmid type presented a particular copy number and produced a specific resistance profile and biological cost, whether alone or coexisting with the other plasmids. Therefore, there was no fitness advantage associated with plasmid coexistence that could explain these common plasmid associations in nature. Using experimental evolution, we showed how H. influenzae Rd was able to completely compensate the fitness cost produced by any of these plasmids. Crucially, once the bacterium has compensated for a first plasmid, the acquisition of new multicopy plasmid(s) did not produced any extra biological cost. We argue therefore that compensatory adaptation pave the way for the acquisition of multiple coexisting ColE1 plasmids.ImportanceAntibiotic resistance is a major concern for human and animal health. Plasmids play a major role in the acquisition and dissemination of antimicrobial resistance genes. In this report we investigate, for the first time, how plasmids are capable to cohabit stably in populations. This coexistence of plasmids is driven by compensatory evolution alleviating the cost of a first plasmid, which potentiates the acquisition of further plasmids at no extra cost. This phenomenon explains the high prevalence of plasmids coexistance in wild type bacteria, which generates multiresistant clones and contributes to the maintenance and spread of antibiotic resistance genes within bacterial populations.


2018 ◽  
Author(s):  
George Taiaroa ◽  
Gregory M. Cook ◽  
Deborah A Williamson

SynopsisBackgroundNext-generation sequencing methods have broad application in addressing increasing antibiotic resistance, with identification of antibiotic resistance genes (ARGs) having direct clinical relevance.ObjectivesHere, we describe the appearance of synthetic vector-associated ARGs in major public next-generation sequence data sets and assemblies, including in environmental samples and high priority pathogenic microorganisms.MethodsA search of selected databases – the National Centre for Biotechnology Information (NCBI) nucleotide collection, NCBI whole genome shotgun sequence contigs and literature-associated European Nucleotide Archive (ENA) datasets, was carried out using sequences characteristic of pUC-family synthetic vectors as a query in BLASTn. Identified hits were confirmed as being of synthetic origin, and further explored through alignment and comparison to primary read sets.ResultsSynthetic vectors are attributed to a range of organisms in each of the NCBI databases searched, including examples belonging to each Kingdom of life. These synthetic vectors are associated with various ARGs, primarily those encoding resistance to beta-lactam antibiotics and aminoglycosides. Synthetic vector associated ARGs are also observed in multiple environmental meta-transcriptome datasets, as shown through analysis of associated ENA primary reads, and are proposed to have led to incorrect statements being made in the literature on the abundance of ARGs.ConclusionsAppearance of synthetic vector-associated ARGs can confound the study of antimicrobial resistance in varied settings, and may have clinical implications in the nearfuture.


2019 ◽  
Vol 9 (3) ◽  
pp. 387 ◽  
Author(s):  
Adriana Osińska ◽  
Ewa Korzeniewska ◽  
Monika Harnisz ◽  
Sebastian Niestępski

Wastewater treatment plants (WWTPs) are an important reservoir in the development of drug resistance phenomenon and they provide a potential route of antibiotic resistance gene (ARGs) dissemination in the environment. The aim of this study was to assess the role of WWTPs in the spread of ARGs. Untreated and treated wastewater samples that were collected from thirteen Polish WWTPs (applying four different modifications of activated sludge–based treatment technology) were analyzed. The quantitative occurrence of genes responsible for the resistance to beta-lactams and tetracyclines was determined using the real-time PCR method. Such genes in the DNA of both the total bacterial population and of the E. coli population were analyzed. Among the tested genes that are responsible for the resistance to beta-lactams and tetracyclines, blaOXA and blaTEM and tetA were dominant, respectively. This study found an insufficient reduction in the quantity of the genes that are responsible for antibiotic resistance in wastewater treatment processes. The results emphasize the need to monitor the presence of genes determining antibiotic resistance in the wastewater that is discharged from treatment plants, as they can help to identify the hazard that treated wastewater poses to public health.


2019 ◽  
Author(s):  
Xue Zhang ◽  
Daniel E. Deatherage ◽  
Hao Zheng ◽  
Stratton J. Georgoulis ◽  
Jeffrey E. Barrick

AbstractPlasmids play a principal role in the spread of antibiotic resistance and other traits by horizontal gene transfer in bacteria. However, newly acquired plasmids generally impose a fitness burden on a cell, and they are lost from a population rapidly if there is not selection to maintain a unique function encoded on the plasmid. Mutations that ameliorate this fitness cost can sometimes eventually stabilize a plasmid in a new host, but they typically do so by inactivating some of its novel accessory genes. In this study, we identified an additional evolutionary pathway that can prolong the maintenance of newly acquired genes encoded on a plasmid. We discovered that propagation of an RSF1010-based IncQ plasmid inEscherichia colioften generated ‘satellite plasmids’ with spontaneous deletions of accessory genes and genes required for plasmid replication. These smaller plasmid variants are nonautonomous genetic parasites. Their presence in a cell drives down the copy number of full-length plasmids, which reduces the burden from the accessory genes without eliminating them entirely. The evolution of satellite plasmids may be favored relative to other plasmid fates because they give a more immediate fitness advantage to a cell’s progeny and because the organization of IncQ plasmids makes them particularly prone to certain deletions during replication. Satellite plasmids also evolved inSnodgrassella alvicolonizing the honey bee gut, suggesting that this mechanism may broadly contribute to the importance of IncQ plasmids as agents of bacterial gene transfer in nature.Significance StatementPlasmids are multicopy DNA elements found in bacteria that replicate independently of a cell’s chromosome. The spread of plasmids carrying antibiotic-resistance genes to new bacterial pathogens is a challenge for treating life-threatening infections. Often plasmids or their accessory genes encoding unique functions are lost soon after transfer into a new cell because they impose a fitness burden. We report that a family of transmissible plasmids can rapidly evolve ‘satellite plasmids’ that replicate as genetic parasites of the original plasmid. Satellite plasmid formation reduces the burden from the newly acquired genes, which may enable them to survive intact for longer after transfer into a new cell and thereby contribute to the spread of antibiotic resistance and other traits within bacterial populations.


2018 ◽  
Author(s):  
G. A. Arango-Argoty ◽  
D. Dai ◽  
A. Pruden ◽  
P. Vikesland ◽  
L. S. Heath ◽  
...  

ABSTRACTDirect selection pressures imposed by antibiotics, indirect pressures by co-selective agents, and horizontal gene transfer are fundamental drivers of the evolution and spread of antibiotic resistance. Therefore, effective environmental monitoring tools should ideally capture not only antibiotic resistance genes (ARGs), but also mobile genetic elements (MGEs) and indicators of co-selective forces, such as metal resistance genes (MRGs). Further, a major challenge towards characterizing potential human risk is the ability to identify bacterial host organisms, especially human pathogens. Historically, short reads yielded by next-generation sequencing technology has hampered confidence in assemblies for achieving these purposes. Here we introduce NanoARG, an online computational resource that takes advantage of long reads produced by MinION nanopore sequencing. Specifically, long nanopore reads enable identification of ARGs in the context of relevant neighboring genes, providing relevant insight into mobility, co-selection, and pathogenicity. NanoARG allows users to upload sequence data online and provides various means to analyze and visualize the data, including quantitative and simultaneous profiling of ARG, MRG, MGE, and pathogens. NanoARG is publicly available and freely accessible at http://bench.cs.vt.edu/nanoARG.


2019 ◽  
Author(s):  
Kira Moon ◽  
Ilnam Kang ◽  
Kwang Seung Park ◽  
Jeong Ho Jeon ◽  
Kihyun lee ◽  
...  

Abstract BackgroundAntibiotic resistance developed by bacteria is a significant threat to global health. Antibiotic resistance genes (ARGs) spread across different bacterial populations through multiple dissemination routes, including horizontal gene transfer mediated by bacteriophages. ARGs carried by bacteriophages are considered especially threatening due to their prolonged persistence in the environment, fast replication rates, and ability to infect phylogenetically remote bacterial hosts. Several studies employing qPCR and viral metagenomics have shown that viral fraction and viral sequence reads in clinical and environmental samples carry many ARGs. However, only a few ARGs have been found in viral contigs assembled from metagenome reads, with most of these genes lacking effective antibiotic resistance phenotypes. Owing to the wide application of viral metagenomics, nevertheless, different classes of ARGs are being continuously found in viral metagenomes acquired from diverse environments. As such, the presence and functionality of ARGs encoded by bacteriophages remain up for debate.ResultsWe evaluated ARGs excavated from viral contigs recovered from urban surface water viral metagenome data. In virome reads and contigs, diverse ARGs, including polymyxin resistance genes, multidrug efflux proteins, and β-lactamases, were identified. In particular, the novel β-lactamases blaHRV-1 and blaHRVM-1 found in this study had unique sequences, forming distinct clades of Class A and subclass B3 β-lactamases, respectively. Minimum inhibitory concentration analyses for E. coli strains harboring blaHRV-1 and blaHRVM-1 and catalytic kinetics of purified HRV-1 and HRVM-1 showed reduced susceptibility to penicillin, narrow- and extended-spectrum cephalosporins, and carbapenems. These genes were also found in bacterial metagenomes, indicating that they were harbored by actively infecting phages.ConclusionOur results showed that viruses in the environment carry as-yet-unreported functional ARGs, albeit in small quantities. We thereby suggest that environmental bacteriophages could be reservoirs of widely variable, unknown ARGs that could be disseminated via virus-host interactions.


Genetics ◽  
2002 ◽  
Vol 162 (4) ◽  
pp. 1525-1532
Author(s):  
Francisco Dionisio ◽  
Ivan Matic ◽  
Miroslav Radman ◽  
Olivia R Rodrigues ◽  
François Taddei

Abstract Conjugative plasmids can mediate gene transfer between bacterial taxa in diverse environments. The ability to donate the F-type conjugative plasmid R1 greatly varies among enteric bacteria due to the interaction of the system that represses sex-pili formations (products of finOP) of plasmids already harbored by a bacterial strain with those of the R1 plasmid. The presence of efficient donors in heterogeneous bacterial populations can accelerate plasmid transfer and can spread by several orders of magnitude. Such donors allow millions of other bacteria to acquire the plasmid in a matter of days whereas, in the absence of such strains, plasmid dissemination would take years. This “amplification effect” could have an impact on the evolution of bacterial pathogens that exist in heterogeneous bacterial communities because conjugative plasmids can carry virulence or antibiotic-resistance genes.


mSystems ◽  
2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Sumayah F. Rahman ◽  
Matthew R. Olm ◽  
Michael J. Morowitz ◽  
Jillian F. Banfield

The process of reconstructing genomes from environmental sequence data (genome-resolved metagenomics) allows unique insight into microbial systems. We apply this technique to investigate how the antibiotic resistance genes of bacteria affect their ability to flourish in the gut under various conditions. Our analysis reveals that strain-level selection in formula-fed infants drives enrichment of beta-lactamase genes in the gut resistome. Using genomes from metagenomes, we built a machine learning model to predict how organisms in the gut microbial community respond to perturbation by antibiotics. This may eventually have clinical applications.


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