scholarly journals Appearance of synthetic vector-associated antibiotic resistance genes in next-generation sequences

2018 ◽  
Author(s):  
George Taiaroa ◽  
Gregory M. Cook ◽  
Deborah A Williamson
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Sequence Data ◽  
Antibiotic Resistance Genes ◽  
Data Sets ◽  
Next Generation ◽  
Beta Lactam ◽  
Sequence Contigs ◽  
Beta Lactam Antibiotics ◽  
Genome Shotgun Sequence

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.

scholarly journals Oral Beta-Lactamase Protects the Canine Gut Microbiome from Oral Amoxicillin-Mediated Damage

2019 ◽  
Vol 7 (5) ◽  
pp. 150 ◽  
Author(s):  
Sheila Connelly ◽  
Brian Fanelli ◽  
Nur A. Hasan ◽  
Rita R. Colwell ◽  
Michael Kaleko
Keyword(s):  
Antibiotic Resistance ◽  
Small Intestine ◽  
Resistance Genes ◽  
Gut Microbiome ◽  
Antibiotic Resistance Genes ◽  
Oral Antibiotic ◽  
Beta Lactamase ◽  
Gi Tract ◽  
Beta Lactam ◽  
Beta Lactam Antibiotics

Antibiotics damage the gut microbiome, which can result in overgrowth of pathogenic microorganisms and emergence of antibiotic resistance. Inactivation of antibiotics in the small intestine represents a novel strategy to protect the colonic microbiota. SYN-004 (ribaxamase) is a beta-lactamase formulated for oral delivery intended to degrade intravenously administered beta-lactam antibiotics in the gastrointestinal (GI) tract. The enteric coating of ribaxamase protects the enzyme from stomach acid and mediates pH-dependent release in the upper small intestine, the site of antibiotic biliary excretion. Clinical benefit was established in animal and human studies in which ribaxamase was shown to degrade ceftriaxone in the GI tract, thereby preserving the gut microbiome, significantly reducing Clostridioides difficile disease, and attenuating antibiotic resistance. To expand ribaxamase utility to oral beta-lactams, delayed release formulations of ribaxamase, SYN-007, were engineered to allow enzyme release in the lower small intestine, distal to the site of oral antibiotic absorption. Based on in vitro dissolution profiles, three SYN-007 formulations were selected for evaluation in a canine model of antibiotic-mediated gut dysbiosis. Dogs received amoxicillin (40 mg/kg, PO, TID) +/- SYN-007 (10 mg, PO, TID) for five days. Serum amoxicillin levels were measured after the first and last antibiotic doses and gut microbiomes were evaluated using whole genome shotgun sequence metagenomics analyses of fecal DNA prior to and after antibiotic treatment. Serum amoxicillin levels did not significantly differ +/- SYN-007 after the first dose for all SYN-007 formulations, while only one SYN-007 formulation did not significantly reduce systemic antibiotic concentrations after the last dose. Gut microbiomes of animals receiving amoxicillin alone displayed significant loss of diversity and emergence of antibiotic resistance genes. In contrast, for animals receiving amoxicillin + SYN-007, microbiome diversities were not altered significantly and the presence of antibiotic resistance genes was reduced. These data demonstrate that SYN-007 diminishes amoxicillin-mediated microbiome disruption and mitigates emergence and propagation of antibiotic resistance genes without interfering with antibiotic systemic absorption. Thus, SYN-007 has the potential to protect the gut microbiome by inactivation of beta-lactam antibiotics when administered by both oral and parenteral routes and to reduce emergence of antibiotic-resistant pathogens.

scholarly journals Novel Soil-Derived Beta-Lactam, Chloramphenicol, Fosfomycin and Trimethoprim Resistance Genes Revealed by Functional Metagenomics

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 378
Author(s):  
Inka Marie Willms ◽  
Maja Grote ◽  
Melissa Kocatürk ◽  
Lukas Singhoff ◽  
Alina Andrea Kraft ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Reference Database ◽  
Functional Metagenomics ◽  
Beta Lactam ◽  
Public Attention ◽  
Soil Ecosystems ◽  
High Level ◽  
Antibiotic Efflux

Antibiotic resistance genes (ARGs) in soil are considered to represent one of the largest environmental resistomes on our planet. As these genes can potentially be disseminated among microorganisms via horizontal gene transfer (HGT) and in some cases are acquired by clinical pathogens, knowledge about their diversity, mobility and encoded resistance spectra gained increasing public attention. This knowledge offers opportunities with respect to improved risk prediction and development of strategies to tackle antibiotic resistance, and might help to direct the design of novel antibiotics, before further resistances reach hospital settings or the animal sector. Here, metagenomic libraries, which comprise genes of cultivated microorganisms, but, importantly, also those carried by the uncultured microbial majority, were screened for novel ARGs from forest and grassland soils. We detected three new beta-lactam, a so far unknown chloramphenicol, a novel fosfomycin, as well as three previously undiscovered trimethoprim resistance genes. These ARGs were derived from phylogenetically diverse soil bacteria and predicted to encode antibiotic inactivation, antibiotic efflux, or alternative variants of target enzymes. Moreover, deduced gene products show a minimum identity of ~21% to reference database entries and confer high-level resistance. This highlights the vast potential of functional metagenomics for the discovery of novel ARGs from soil ecosystems.

scholarly journals Monitoring and Evaluation of Antibiotic Resistance Genes in Three Rivers in Northeast China

2021 ◽  
Author(s):  
Chen Zhao ◽  
Chenyu Li ◽  
Xiaoming Wang ◽  
Zhuosong Cao ◽  
Chao Gao ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
River Water ◽  
Resistance Genes ◽  
Northeast China ◽  
Pathogenic Bacteria ◽  
Respiratory Infections ◽  
Antibiotic Resistance Genes ◽  
Distribution Characteristics ◽  
Beta Lactam ◽  
Three Rivers

Abstract Background: Antibiotic resistance genes (ARGs) have become an important public health problem. In this study, we used metagenomic sequencing to analyze the composition of ARGs in certain original habitats of northeast China, comprising three different rivers and riverbank soils of the Heilongjiang River, Tumen River, and Yalu River. Results: Twenty types of ARG were detected in every water sample. The major ARGs were multidrug resistance genes, at approximately 0.5 copies/16s rRNA, accounting for 57.5% of the total ARG abundance. The abundance of multidrug, bacitracin, beta-lactam, macrolide‑lincosamide‑streptogramin, sulfonamide, fosmidomycin, and polymyxin resistance genes covered 96.9% of the total ARG abundance. No significant ecological boundary of ARG diversity was observed. The compositions of the resistance genes in the three rivers were very similar to each other, and 92.1% of ARG subtypes were shared by all water samples. Except for vancomycin resistance genes, almost all ARGs in riverbank soils were detected in the river water. About 31.05% ARGs were carried by Pseudomonas. Opportunistic pathogenic bacteria carrying resistance genes were mainly related to diarrhea and respiratory infections. Multidrug and beta-lactam resistance genes correlated positively with mobile genetic elements (MGEs), indicating a potential risk of diffusion.Conclusions: The composition of ARGs in three different rivers was similar, indicating that climate played an important role in ARG occurrence. ARG subtypes in river water were almost completely the same as those in riverbank soil. ARGs had no significant geographical distribution characteristics. Many ARGs were carried by human pathogenic bacteria related to human diarrhea and respiratory infections, such as Pseudomonas aeruginosa and Aeromonas caviae. In general, our results provide a valuable dataset of river water ARG distribution in northeast China. The related ecological geography distribution characteristics should be further explored.

scholarly journals Longitudinal assessment of antibiotic resistance gene profiles from the infant gut microbiome

2019 ◽  
Author(s):  
Evelyn Loo ◽  
Amanda Zain ◽  
Gaik Chin Yap ◽  
Rikky W Purbojati ◽  
Daniela I Drautz-Moses ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Cohort Study ◽  
Resistance Gene ◽  
Resistance Genes ◽  
Antibiotic Resistance Gene ◽  
Antibiotic Resistance Genes ◽  
Longitudinal Cohort Study ◽  
First Year ◽  
Beta Lactam ◽  
First Year Of Life

Abstract Background: The rapid spread of multidrug- resistant pathogenic bacteria is a worldwide public health concern. Given the high carriage rate of extended spectrum beta-lactamase (ESBL)- producing Enterobacteriaceae in Asia, we aimed to evaluate community prevalence and dynamics by studying the longitudinal changes in antibiotic resistance gene (ARG) profiles and prevalence of ESBL-producing E coli and K. pneumoniae in the intestinal microbiome of infants participating in the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, a longitudinal cohort study of pregnant women and their infants. Methods: We analysed the antibiotic resistance genes profile in the first year of life among 75 infants who had stool samples collected at multiple timepoints using metagenomics. Results: The mean number of ARGs per infant increased with age. The most common ARGs identified confer resistance to aminoglycoside, beta-lactam, macrolide and tetracycline antibiotics; all infants harboured these antibiotic resistance genes at some point in the first year of life. Few ARGs persisted throughout the first year of life. Beta-lactam resistant Escherichia coli and Klebsiella pneumoniae were detected in 4 (5.3%) and 32 (42.7%) of subjects respectively. Conclusion: In this longitudinal cohort study of healthy infants living in a region with high endemic antibacterial resistance, we demonstrate that majority of the infants harboured a number of antibiotic resistance genes in their gut and showed that the infant gut resistome is diverse and dynamic over the first year of life.

scholarly journals Longitudinal assessment of antibiotic resistance gene profiles in gut microbiomes of infants at risk of eczema

2020 ◽  
Author(s):  
Evelyn Loo ◽  
Amanda Zain ◽  
Gaik Chin Yap ◽  
Rikky W Purbojati ◽  
Daniela I Drautz-Moses ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Cohort Study ◽  
Resistance Genes ◽  
Pathogenic Bacteria ◽  
Antibiotic Resistance Gene ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
First Year ◽  
Beta Lactam ◽  
First Year Of Life

Abstract Background While there is increasing knowledge about the gut microbiome, the factors influencing and the significance of the gut resistome are still not well understood. Infant gut commensals risk transferring multidrug-resistant antibiotic resistance genes (ARGs) to pathogenic bacteria. The rapid spread of multidrug-resistant pathogenic bacteria is a worldwide public health concern. Better understanding the naïve infant gut resistome may build the evidence base for antimicrobial stewardship in both humans and in the food industry. Given the high carriage rate of extended spectrum beta-lactamase (ESBL)- producing Enterobacteriaceae in Asia, we aimed to evaluate community prevalence, dynamics, and longitudinal changes in antibiotic resistance gene (ARG) profiles and prevalence of ESBL-producing .E coli and K. pneumoniae in the intestinal microbiome of infants participating in the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, a longitudinal cohort study of pregnant women and their infants. Methods We analysed ARGs in the first year of life among 75 infants who had stool samples collected at multiple timepoints using metagenomics. Results The mean number of ARGs per infant increased with age. The most common ARGs identified confer resistance to aminoglycoside, beta-lactam, macrolide and tetracycline antibiotics; all infants harboured these antibiotic resistance genes at some point in the first year of life. Few ARGs persisted throughout the first year of life. Beta-lactam resistant Escherichia coli and Klebsiella pneumoniae were detected in 4 (5.3%) and 32 (42.7%) of subjects respectively. Conclusion In this longitudinal cohort study of infants living in a region with high endemic antibacterial resistance, we demonstrate that the majority of the infants harboured several antibiotic resistance genes in their gut and showed that the infant gut resistome is diverse and dynamic over the first year of life.

Case report: Detection of aadB and tet (39) on the plasmid of Acinetobacter baumannii TN81 in Vietnam through next-generation sequencing and bioinformatics analysis

2021 ◽  
Vol 31 (4) ◽  
pp. 51-60
Author(s):  
Vu Nhi Ha ◽  
Kieu Chi Thanh ◽  
Nguyen Thai Son ◽  
Dao Van Thang ◽  
Tran Huy Hoang
Keyword(s):  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Resistance Genes ◽  
De Novo Assembly ◽  
De Novo ◽  
Antibiotic Resistance Genes ◽  
Common Mechanism ◽  
Genes Encoding ◽  
Short Read Sequence ◽  
Genome Shotgun Sequence

Acinetobacter baumannii (A. baumannii) is currently ranked as the frst concern for the development of new antibiotics due to its capacity of resistance to all available families of antibiotics. The most common mechanism of antibiotic resistance development in A. baumannii is through the acquisition of mobile genetic elements such as plasmid, transposon and integrons carrying resistance genes. A. baumannii strain TN81 was isolated from sputum specimen of a 45-year-old man at Thanh Nhan Hospital (Hanoi, Vietnam) and confrmed to be a multidrug resistance strain with high minimum inhibitory concentration value of 8/9 type of antibiotics, especially colistin. De novo assembly of the whole genome shotgun sequence of strain TN81 yielded an estimated genome size of 3,739,193 bp with 593 contigs and N50 is 9,126 bp. MLST analysis showed that TN81 belongs to ST164, which was frst reported as genome assembly in Vietnam. Resistance genes identifcation through database found that TN81 contained 12 genes encoding for antibiotic resistance. Notably, we performed de novo assembly of plasmid through short read sequence and identifed two potential plasmid-encoded antibiotic resistance genes (ant(2’’)-Ia / aadB and tet (39), which were reported for the first time as in ST164 group. This study aimed to investigate the plasmid-containing antibiotic resistance genes from a nosocomial isolate of Acinetobacter baumannii. Conclusively, all of these results would be crucial information on antibiotic resistance in A. baumannii in Vietnam.

scholarly journals NanoARG: A web service for identification of antimicrobial resistance elements from nanopore-derived environmental metagenomes

2018 ◽  
Author(s):  
G. A. Arango-Argoty ◽  
D. Dai ◽  
A. Pruden ◽  
P. Vikesland ◽  
L. S. Heath ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Sequence Data ◽  
Antibiotic Resistance Genes ◽  
Metal Resistance ◽  
Direct Selection ◽  
Human Pathogens ◽  
Next Generation Sequencing Technology ◽  
Monitoring Tools ◽  
Long Reads

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.

scholarly journals Monitoring and Evaluation of Antibiotic Resistance Genes in Three Rivers in Northeast China

2021 ◽  
Author(s):  
Chen Zhao ◽  
Chenyu Li ◽  
Xiaoming Wang ◽  
Zhuosong Cao ◽  
Chao Gao ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
River Water ◽  
Resistance Genes ◽  
Northeast China ◽  
Pathogenic Bacteria ◽  
Respiratory Infections ◽  
Antibiotic Resistance Genes ◽  
Distribution Characteristics ◽  
Beta Lactam ◽  
Three Rivers

Abstract Background: Antibiotic resistance genes (ARGs) have become an important public health problem. In this study, we used metagenomic sequencing to analyze the composition of ARGs in certain original habitats of northeast China, comprising three different rivers and riverbank soils of the Heilongjiang River, Tumen River, and Yalu River. Results: Twenty types of ARG were detected in every water sample. The major ARGs were multidrug resistance genes, at approximately 0.5 copies/16s rRNA, accounting for 57.5% of the total ARG abundance. The abundance of multidrug, bacitracin, beta-lactam, macrolide‑lincosamide‑streptogramin, sulfonamide, fosmidomycin, and polymyxin resistance genes covered 96.9% of the total ARG abundance. No significant ecological boundary of ARG diversity was observed. The compositions of the resistance genes in the three rivers were very similar to each other, and 92.1% of ARG subtypes were shared by all water samples. Except for vancomycin resistance genes, almost all ARGs in riverbank soils were detected in the river water. About 31.05% ARGs were carried by Pseudomonas. Opportunistic pathogenic bacteria carrying resistance genes were mainly related to diarrhea and respiratory infections. Multidrug and beta-lactam resistance genes correlated positively with mobile genetic elements (MGEs), indicating a potential risk of diffusion.Conclusions: The composition of ARGs in three different rivers was similar, indicating that climate played an important role in ARG occurrence. ARG subtypes in river water were almost completely the same as those in riverbank soil. ARGs had no significant geographical distribution characteristics. Many ARGs were carried by human pathogenic bacteria related to human diarrhea and respiratory infections, such as Pseudomonas aeruginosa and Aeromonas caviae. In general, our results provide a valuable dataset of river water ARG distribution in northeast China. The related ecological geography distribution characteristics should be further explored.

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