scholarly journals MetaCherchant - an algorithm for analyzing genomic environment of antibiotic resistance gene in gut microbiota

2017 ◽  
Author(s):  
Evgenii I. Olekhnovich ◽  
Artem T. Vasilyev ◽  
Vladimir I. Ulyantsev ◽  
Alexander V. Tyakht

AbstractAntibiotic resistance is an important global public health problem. Human gut human microbiota is an accumulator of resistance genes potentially providing them to pathogens. It is important to develop tools for identifying the mechanisms of how resistance is transmitted between gut microbial species and pathogens. We developed MetaCherchant - an algorithm for extracting the genomic environment of antibiotic resistance genes from metagenomic data in the form of a graph. The algorithm was validated on simulated datasets and applied to new "shotgun" metagenomes of gut microbiota from patients with Helicobacter pylori who underwent antibiotic therapy. Genomic context was reconstructed for several dominant resistance genes; taxonomic annotation of the context showed the species carrying the genes. Application of MetaCherchant in differential mode produced specific graph structures suggesting the evidence of possible resistance gene transmission within a mobile element that occurred as a result of the antibiotic therapy. MetaCherchant is a promising tool giving researchers an opportunity to get an insight into dynamics of resistance transmission in vivo based on metagenomic data.


2018 ◽  
Author(s):  
Karkman Antti ◽  
Pärnänen Katariina ◽  
Larsson D.G. Joakim

AbstractDischarge of treated sewage leads to release of antibiotic resistant bacteria, resistance genes and antibiotic residues to the environment. Such pollution can directly contribute to increased morbidity caused by the transmission of resistant fecal pathogens. Residual antibiotics in wastewaters have been speculated to select for resistant bacteria and thereby promote the evolution and emergence of new resistance factors. Increased abundance of antibiotic resistance genes in sewage and sewage-impacted environments may, however, simply be a result of fecal contamination with resistant bacteria rather than caused by an on-site selection pressure. In this study we have disentangled these two alternative scenarios by relating the relative resistance gene abundance to the accompanying extent of fecal pollution in publicly available metagenomic data. This was possible by analyzing the abundance of a newly discovered phage which is exceptionally abundant in, and specific to, human feces. The presence of resistance genes could largely be explained by fecal pollution, with no clear signs of selection in the environment, the only exception being environments polluted by very high levels of antibiotics from manufacturing where selection is evident. Our results demonstrate the necessity to take in to account the fecal pollution levels to avoid making erroneous assumptions regarding environmental selection of antibiotic resistance. The presence or absence of selection pressure has major implications for what the risk scenarios are (transmission versus evolution) and for what mitigations (reducing pathogenic bacteria or selective agents) should be prioritized to reduce health risks related to antibiotic resistance in the environment.



Diversity ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 230
Author(s):  
Shan Wan ◽  
Min Xia ◽  
Jie Tao ◽  
Yanjun Pang ◽  
Fugen Yu ◽  
...  

In this study, we used a metagenomic approach to analyze microbial communities, antibiotic resistance gene diversity, and human pathogenic bacterium composition in two typical landfills in China. Results showed that the phyla Proteobacteria, Bacteroidetes, and Actinobacteria were predominant in the two landfills, and archaea and fungi were also detected. The genera Methanoculleus, Lysobacter, and Pseudomonas were predominantly present in all samples. sul2, sul1, tetX, and adeF were the four most abundant antibiotic resistance genes. Sixty-nine bacterial pathogens were identified from the two landfills, with Klebsiella pneumoniae, Bordetella pertussis, Pseudomonas aeruginosa, and Bacillus cereus as the major pathogenic microorganisms, indicating the existence of potential environmental risk in landfills. In addition, KEGG pathway analysis indicated the presence of antibiotic resistance genes typically associated with human antibiotic resistance bacterial strains. These results provide insights into the risk of pathogens in landfills, which is important for controlling the potential secondary transmission of pathogens and reducing workers’ health risk during landfill excavation.



2001 ◽  
Vol 45 (11) ◽  
pp. 2991-3000 ◽  
Author(s):  
Bianca Hochhut ◽  
Yasmin Lotfi ◽  
Didier Mazel ◽  
Shah M. Faruque ◽  
Roger Woodgate ◽  
...  

ABSTRACT Many recent Asian clinical Vibrio cholerae E1 Tor O1 and O139 isolates are resistant to the antibiotics sulfamethoxazole (Su), trimethoprim (Tm), chloramphenicol (Cm), and streptomycin (Sm). The corresponding resistance genes are located on large conjugative elements (SXT constins) that are integrated into prfC on the V. cholerae chromosome. We determined the DNA sequences of the antibiotic resistance genes in the SXT constin in MO10, an O139 isolate. In SXTMO10, these genes are clustered within a composite transposon-like structure found near the element's 5′ end. The genes conferring resistance to Cm (floR), Su (sulII), and Sm (strA and strB) correspond to previously described genes, whereas the gene conferring resistance to Tm, designated dfr18, is novel. In some other O139 isolates the antibiotic resistance gene cluster was found to be deleted from the SXT-related constin. The El Tor O1 SXT constin, SXTET, does not contain the same resistance genes as SXTMO10. In this constin, the Tm resistance determinant was located nearly 70 kbp away from the other resistance genes and found in a novel type of integron that constitutes a fourth class of resistance integrons. These studies indicate that there is considerable flux in the antibiotic resistance genes found in the SXT family of constins and point to a model for the evolution of these related mobile elements.



2019 ◽  
Author(s):  
Evelyn Loo ◽  
Amanda Zain ◽  
Gaik Chin Yap ◽  
Rikky W Purbojati ◽  
Daniela I Drautz-Moses ◽  
...  

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.



2019 ◽  
Vol 71 (2) ◽  
pp. 419-421
Author(s):  
Quentin Le Bastard ◽  
Pajau Vangay ◽  
Eric Batard ◽  
Dan Knights ◽  
Emmanuel Montassier

Abstract Little is known about the effect of human migration on gut microbiome antibiotic resistance gene (ARG) carriage. Using deep shotgun stool metagenomics analysis, we found a rapid increase in gut microbiome ARG richness and abundance in women from 2 independent ethnic groups relocating from Thailand to the United States.



2010 ◽  
Vol 59 (7) ◽  
pp. 804-807 ◽  
Author(s):  
David Skurnik ◽  
Raymond Ruimy ◽  
Derren Ready ◽  
Etienne Ruppe ◽  
Claire Bernède-Bauduin ◽  
...  

The mercury resistance gene merA has often been found together with antibiotic resistance genes in human commensal Escherichia coli. To study this further, we analysed mercury resistance in collections of strains from various populations with different levels of mercury exposure and various levels of antibiotic resistance. The first population lived in France and had no known mercury exposure. The second lived in French Guyana and included a group of Wayampi Amerindians with a known high exposure to mercury. Carriage rates of mercury resistance were assessed by measuring the MIC and by detecting the merA gene. Mercury-resistant E. coli was found significantly more frequently in the populations that had the highest carriage rates of antibiotic-resistant E. coli and in parallel antibiotic resistance was higher in the population living in an environment with a high exposure to mercury, suggesting a possible co-selection. Exposure to mercury might be a specific driving force for the acquisition and maintenance of mobile antibiotic resistance gene carriage in the absence of antibiotic selective pressure.



Author(s):  
Yaying Li ◽  
Hongkai Liao ◽  
Huaiying Yao

High-throughput quantitative PCR combined with Illumina sequencing and network analysis were used to characterize the antibiotic resistance gene (ARG) profiles in air-conditioning filters from different environments. In total, 177 ARGs comprising 10 ARG types were determined. The detectable numbers and the relative abundance of ARGs in hospitals and farms were significantly higher than those in city and village residences. Compared to hospitals, farms had a higher level of tetracycline, multidrug, integrase, and macrolide–lincosamide–streptogramin (MLS) B resistance genes but a lower level of beta-lactam resistance genes. The bl3_cpha gene was the most abundant resistance gene subtype in hospital samples with an abundance of 2.01 × 10−4 copies/16S rRNA, while a level of only 5.08 × 10−12 copies/16S rRNA was observed in farm samples. There was no significant difference in bacterial diversity among the hospitals, farms, and residences, and Proteobacteria was the most abundant phylum. Network analysis revealed that Proteobacteria and Actinobacteria were possible hosts of the beta-lactam, MLSB, aminoglycoside, multidrug, sulfonamide, and tetracycline resistance genes. The results demonstrate that ARGs exist in indoor environments and that farms and hospitals are important sources. This study provides a useful reference for understanding the distribution patterns and risk management of ARGs in indoor environments.



2016 ◽  
Vol 62 (2) ◽  
pp. 353-359 ◽  
Author(s):  
G Terrance Walker ◽  
Tony J Rockweiler ◽  
Rossio K Kersey ◽  
Kelly L Frye ◽  
Susan R Mitchner ◽  
...  

Abstract BACKGROUND Multiantibiotic-resistant bacteria pose a threat to patients and place an economic burden on health care systems. Carbapenem-resistant bacilli and extended-spectrum β-lactamase (ESBL) producers drive the need to screen infected and colonized patients for patient management and infection control. METHODS We describe a multiplex microfluidic PCR test for perianal swab samples (Acuitas® MDRO Gene Test, OpGen) that detects the vancomycin-resistance gene vanA plus hundreds of gene subtypes from the carbapenemase and ESBL families Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), Verona integron-mediated metallo-β-lactamase (VIM), imipenemase metallo-β-lactamase (IMP), OXA-23, OXA-48, OXA-51, CTX-M-1, and CTX-M-2, regardless of the bacterial species harboring the antibiotic resistance. RESULTS Analytical test sensitivity per perianal swab is 11–250 CFU of bacteria harboring the antibiotic resistance genes. Test throughput is 182 samples per test run (1820 antibiotic resistance gene family results). We demonstrate reproducible test performance and 100% gene specificity for 265 clinical bacterial organisms harboring a variety of antibiotic resistance genes. CONCLUSIONS The Acuitas MDRO Gene Test is a sensitive, specific, and high-throughput test to screen colonized patients and diagnose infections for several antibiotic resistance genes directly from perianal swab samples, regardless of the bacterial species harboring the resistance genes.



2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Amy Langdon ◽  
◽  
Drew J. Schwartz ◽  
Christopher Bulow ◽  
Xiaoqing Sun ◽  
...  

Abstract Background Once antibiotic-resistant bacteria become established within the gut microbiota, they can cause infections in the host and be transmitted to other people and the environment. Currently, there are no effective modalities for decreasing or preventing colonization by antibiotic-resistant bacteria. Intestinal microbiota restoration can prevent Clostridioides difficile infection (CDI) recurrences. Another potential application of microbiota restoration is suppression of non-C. difficile multidrug-resistant bacteria and overall decrease in the abundance of antibiotic resistance genes (the resistome) within the gut microbiota. This study characterizes the effects of RBX2660, a microbiota-based investigational therapeutic, on the composition and abundance of the gut microbiota and resistome, as well as multidrug-resistant organism carriage, after delivery to patients suffering from recurrent CDI. Methods An open-label, multi-center clinical trial in 11 centers in the USA for the safety and efficacy of RBX2660 on recurrent CDI was conducted. Fecal specimens from 29 of these subjects with recurrent CDI who received either one (N = 16) or two doses of RBX2660 (N = 13) were analyzed secondarily. Stool samples were collected prior to and at intervals up to 6 months post-therapy and analyzed in three ways: (1) 16S rRNA gene sequencing for microbiota taxonomic composition, (2) whole metagenome shotgun sequencing for functional pathways and antibiotic resistome content, and (3) selective and differential bacterial culturing followed by isolate genome sequencing to longitudinally track multidrug-resistant organisms. Results Successful prevention of CDI recurrence with RBX2660 correlated with taxonomic convergence of patient microbiota to the donor microbiota as measured by weighted UniFrac distance. RBX2660 dramatically reduced the abundance of antibiotic-resistant Enterobacteriaceae in the 2 months after administration. Fecal antibiotic resistance gene carriage decreased in direct relationship to the degree to which donor microbiota engrafted. Conclusions Microbiota-based therapeutics reduce resistance gene abundance and resistant organisms in the recipient gut microbiome. This approach could potentially reduce the risk of infections caused by resistant organisms within the patient and the transfer of resistance genes or pathogens to others. Trial registration ClinicalTrials.gov, NCT01925417; registered on August 19, 2013.



2020 ◽  
Author(s):  
Kang Kang ◽  
Lejla Imamovic ◽  
Maria-Anna Misiakou ◽  
Maria Bornakke Sørensen ◽  
Yoshitaro Heshiki ◽  
...  

Abstract Background. Oral antibiotics are commonly prescribed to non-hospitalized adults. However, antibiotic-induced changes on the human gut microbiome are often investigated in cohorts with pre-existing health conditions and/or concomitant medication, leaving the effects of antibiotics not completely understood.Results. We used a combination of omic approaches to comprehensively assess the effects of antibiotics on the gut microbiota and particularly the gut resistome of a small cohort of healthy adults. We observed that 3 to 19 species per individual proliferated during antibiotic treatment and Gram-negative species expanded significantly in relative abundance. While the overall relative abundance of antibiotic resistance gene homologues did not significantly change, antibiotic-specific gene homologues with presumed resistance towards the administered antibiotics were common in proliferating species and significantly increased in relative abundance. Virome sequencing and plasmid analysis showed the expansion of antibiotic-specific resistance gene homologues even three months after antibiotic administration, while paired-end read analysis suggested their dissemination among different species.Conclusions. These results suggest that antibiotic treatment can lead to a persistent expansion of antibiotic resistance genes in the human gut microbiota and provide further data in support of good antibiotic stewardship.



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