| 1. |
- Boulund, Fredrik, 1985, et al.
(författare)
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Computational discovery and functional validation of novel fluoroquinolone resistance genes in public metagenomic data sets
- 2017
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 18:1, s. Art 682-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fluoroquinolones are broad-spectrum antibiotics used to prevent and treat a wide range of bacterial infections. Plasmid-mediated qnr genes provide resistance to fluoroquinolones in many bacterial species and are increasingly encountered in clinical settings. Over the last decade, several families of qnr genes have been discovered and characterized, but their true prevalence and diversity still remain unclear. In particular, environmental and host-associated bacterial communities have been hypothesized to maintain a large and unknown collection of qnr genes that could be mobilized into pathogens. Results: In this study we used computational methods to screen genomes and metagenomes for novel qnr genes. In contrast to previous studies, we analyzed an almost 20-fold larger dataset comprising almost 13 terabases of sequence data. In total, 362,843 potential qnr gene fragments were identified, from which 611 putative qnr genes were reconstructed. These gene sequences included all previously described plasmid-mediated qnr gene families. Fifty-two of the 611 identified qnr genes were reconstructed from metagenomes, and 20 of these were previously undescribed. All of the novel qnr genes were assembled from metagenomes associated with aquatic environments. Nine of the novel genes were selected for validation, and six of the tested genes conferred consistently decreased susceptibility to ciprofloxacin when expressed in Escherichia coli. Conclusions: The results presented in this study provide additional evidence for the ubiquitous presence of qnr genes in environmental microbial communities, expand the number of known qnr gene variants and further elucidate the diversity of this class of resistance genes. This study also strengthens the hypothesis that environmental bacterial communities act as sources of previously uncharacterized qnr genes.
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| 2. |
- Ansin, Caroline, 1996, et al.
(författare)
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Simulation and Field Measurements of the Long-term Rail Surface Damage due to Plasticity, Wear and Surface Rolling Contact Fatigue Cracks in a Curve
- 2022
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Ingår i: CM 2022 - 12th International Conference on Contact Mechanics and Wear of Rail/Wheel Systems, Conference Proceedings. ; , s. 591-601
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Konferensbidrag (refereegranskat)abstract
- A methodology that simulates the long-term rail surface damage in a cross-section of a curve for a given traffic scenario is presented. The numerical model considers plastic deformation, wear, and initiation of rolling contact fatigue (RCF) surface cracks. The models and simulations are calibrated and validated, respectively, against field profile measurement data.
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| 3. |
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| 4. |
- Bengtsson-Palme, Johan, 1985, et al.
(författare)
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Shotgun metagenomics reveals a wide array of antibiotic resistance genes and mobile elements in a polluted lake in India
- 2014
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Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 5:648
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Tidskriftsartikel (refereegranskat)abstract
- There is increasing evidence for an environmental origin of many antibiotic resistance genes. Consequently, it is important to identify environments of particular risk for selecting and maintaining such resistance factors. In this study, we described the diversity of antibiotic resistance genes in an Indian lake subjected to industrial pollution with fluoroquinolone antibiotics. We also assessed the genetic context of the identified resistance genes, to try to predict their genetic transferability. The lake harbored a wide range of resistance genes (81 identified gene types) against essentially every major class of antibiotics, as well as genes responsible for mobilization of genetic material. Resistance genes were estimated to be 7000 times more abundant than in a Swedish lake included for comparison, where only eight resistance genes were found. The sul2 and qnrD genes were the most common resistance genes in the Indian lake. Twenty-six known and 21 putative novel plasmids were recovered in the Indian lake metagenome, which, together with the genes found, indicate a large potential for horizontal gene transfer through conjugation. Interestingly, the microbial community of the lake still included a wide range of taxa, suggesting that, across most phyla, bacteria has adapted relatively well to this highly polluted environment. Based on the wide range and high abundance of known resistance factors we have detected, it is plausible that yet unrecognized resistance genes are also present in the lake. Thus, we conclude that environments polluted with waste from antibiotic manufacturing could be important reservoirs for mobile antibiotic resistance genes.
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| 5. |
- Boulund, Fredrik, 1985, et al.
(författare)
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A novel method to discover fluoroquinolone antibiotic resistance (qnr) genes in fragmented nucleotide sequences
- 2012
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Broad-spectrum fluoroquinolone antibiotics are central in modern health care and are used to treat and prevent a wide range of bacterial infections. The recently discovered qnr genes provide a mechanism of resistance with the potential to rapidly spread between bacteria using horizontal gene transfer. As for many antibiotic resistance genes present in pathogens today, qnr genes are hypothesized to originate from environmental bacteria. The vast amount of data generated by shotgun metagenomics can therefore be used to explore the diversity of qnr genes in more detail. RESULTS: In this paper we describe a new method to identify qnr genes in nucleotide sequence data. We show, using cross-validation, that the method has a high statistical power of correctly classifying sequences from novel classes of qnr genes, even for fragments as short as 100 nucleotides. Based on sequences from public repositories, the method was able to identify all previously reported plasmid-mediated qnr genes. In addition, several fragments from novel putative qnr genes were identified in metagenomes. The method was also able to annotate 39 chromosomal variants of which 11 have previously not been reported in literature. CONCLUSIONS: The method described in this paper significantly improves the sensitivity and specificity of identification and annotation of qnr genes in nucleotide sequence data. The predicted novel putative qnr genes in the metagenomic data support the hypothesis of a large and uncharacterized diversity within this family of resistance genes in environmental bacterial communities. An implementation of the method is freely available at http://bioinformatics.math.chalmers.se/qnr/.
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| 6. |
- Flach, Carl-Fredrik, 1977, et al.
(författare)
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Functional verification of computationally predicted qnr genes
- 2013
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Ingår i: Annals of Clinical Microbiology and Antimicrobials. - : Springer Science and Business Media LLC. - 1476-0711. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background The quinolone resistance (qnr) genes are widely distributed among bacteria. We recently developed and applied probabilistic models to identify tentative novel qnr genes in large public collections of DNA sequence data including fragmented metagenomes. Findings: By using inducible recombinant expressions systems the functionality of four identified qnr candidates were evaluated in Escherichia coli. Expression of several known qnr genes as well as two novel candidates provided fluoroquinolone resistance that increased with elevated inducer concentrations. The two novel, functionally verified qnr genes are termed Vfuqnr and assembled qnr 1. Co-expression of two qnr genes suggested non-synergistic action. Conclusion The combination of a computational model and recombinant expression systems provides opportunities to explore and identify novel antibiotic resistance genes in both genomic and metagenomic datasets.
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| 7. |
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| 8. |
- Sedigh, Amir, et al.
(författare)
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Perfusion of Porcine Kidneys With Macromolecular Heparin Reduces Early Ischemia Reperfusion Injury
- 2019
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Ingår i: Transplantation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0041-1337 .- 1534-6080. ; 103:2, s. 420-427
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previously, we have been able to demonstrate the possibility of coating the inner surface of the renal arteries in porcine kidneys with a heparin conjugate during hypothermic machine perfusion (HMP). The purpose of this study was to assess the efficacy of this treatment in reducing early ischemia-reperfusion injury.Method: Brain death was induced in male landrace pigs by stepwise volume expansion of an epidural balloon catheter until negative cerebral perfusion pressure (CPP) was obtained. Both kidneys (matched pairs; n = 6 + 6) were preserved for 20 hours byHMP during which 50mg heparin conjugate was added to one of the HMP systems (treated group). A customized ex vivo normothermic oxygenated perfusion (NP) system with added exogenous creatinine was used to evaluate early kidney function. Blood, urine and histological samples were collected during the subsequent 3 hours of NP.Results: Kidney weight was lower at the end of NP (P = 0.017) in the treated group compared with control kidneys. The rate of decline in creatinine level was faster (P = 0.024), total urinary volume was higher (P = 0.031), and the level of urine neutrophil gelatinase-associated lipocalin (NGAL) was lower (P = 0.031) in the treated group. Histologically, less tubular changes were seen (P = 0.046). During NP intrarenal resistance remained lower (P < 0.0001) in the treated group.Conclusions: Perfusion of porcine kidneys with heparin conjugate during HMP reduces preservation injury and improves organ function shortly after reperfusion. No increased risk of bleeding was seen in this setup. This protective strategy may potentially improve the quality of transplanted kidneys in the clinical setting.
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| 9. |
- Zou, Yiming, 1985-, et al.
(författare)
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Effect of Sulphur and Phosphorous Doping on the Growth Rate of CVD Diamond (111)
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Ingår i: Thin Solid Films. - 0040-6090 .- 1879-2731.
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Tidskriftsartikel (refereegranskat)abstract
- The purpose with the present study has been to theoretically investigate the effect of P (or S) doping on the diamond growth rate. The highly symmetric diamond (111) surface, terminated by H atoms, was thereby carefully investigated using density functional theory calculations under periodic boundary conditions. It was shown that both the thermodynamic and kinetic aspects of P (or S) doping during diamond growth will be severely affected by the dopants (as compared with the non-doped situations). More specifically, the results showed that P (positioned within the 2nd, 3rd or 4th layer), will cause an enhancement in the growth rate. On the other hand, any growth rate improvement do only occur when positioning S in the 4th atomic C layer. With S in atomic layers 1, 2 and 3, the growth rates were observed to decrease. These observations did correlate with experimental results.
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| 10. |
- Zou, Yiming, 1985-, et al.
(författare)
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Effect of Sulphur and Phosphorous Doping on the Growth Rate of CVD Diamond (111)
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Ingår i: Thin Solid Films. - 0040-6090 .- 1879-2731.
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Tidskriftsartikel (refereegranskat)abstract
- The purpose with the present study has been to theoretically investigate the effect of P (or S) doping on the diamond growth rate. The highly symmetric diamond (111) surface, terminated by H atoms, was thereby carefully investigated using density functional theory calculations under periodic boundary conditions. It was shown that both the thermodynamic and kinetic aspects of P (or S) doping during diamond growth will be severely affected by the dopants (as compared with the non-doped situations). More specifically, the results showed that P (positioned within the 2nd, 3rd or 4th layer), will cause an enhancement in the growth rate. On the other hand, any growth rate improvement do only occur when positioning S in the 4th atomic C layer. With S in atomic layers 1, 2 and 3, the growth rates were observed to decrease. These observations did correlate with experimental results.
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