| 1. |
- Andersson, Robin, 1990, et al.
(författare)
-
EMBRACE: The emotion sharing bracelet
- 2015
-
Ingår i: Proceedings of SIDeR’15 – student interaction design research conference.
-
Konferensbidrag (refereegranskat)abstract
- In this study we present Embrace; a wearable device that explores the potential of wearable technology harnessing the affordance of human form and deformable displays. We research new ways of communicating with loved ones in order to improve the experience of connectedness when they are apart. Embrace is a wearable device in the form of a bracelet that shares emotion between peers by providing both visual and haptic feedback. Other devices like smartphones and tablets have a rigid form and material. In contrast, the deformable display used in Embrace enables the user to wear the technology seamlessly on the body. The haptic feedback for sharing emotions is believed to provide a different experience since the physical sensation is more close to feeling heartbeats, hugs, and skin contact, compared to only visual information of today’s mobile devices.
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| 2. |
- Berglund, Andreas, et al.
(författare)
-
15 koncept för bättre ergonomi : Inom äldreomsorg, fysioterapi, däckmontering och varuhantering
- 2015
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Rapport (populärvet., debatt m.m.)abstract
- Den här boken är resultatet av en kurs i ergonomi vid Teknisk design, Luleå tekniska universitet, våren 2015. 15 kursdeltagare har under 10 veckor använt designmetodik och ergonomiska teorier och metoder för att utveckla 15 konceptuella förbättringsförslag baserade på de 4 undersökta kontexterna äldreomsorg, fysioterapi, däckmontering och varuhantering. Fokus för ergonomi inom området teknisk design är att se till att all design, oavsett vilket system det avser, kompletterar människans styrkor och förmågor. Vi ska kort och gott se till att arbetsuppgifter, utrustning, apparater, processer, miljöer och organisationer utformas med människan som utgångspunkt, istället för att tvinga människan att anpassa sig med olika former av överbelastning som möjlig påföljd. För att uppnå detta behöver vi förstå och designa för den variabilitet som är representerad bland oss människor: vi är olika, har olika åldrar, storlek, styrka, kognitiv förmåga, erfarenheter, förväntningar och mål. Att tillämpa ergonomi betyder att studera hur människor interagerar med produkter, processer, miljöer och system för att förbättra dem, dvs. göra dem enklare, säkrare, bekvämare och effektivare att använda. För att kunna göra det behöver vi kunskap om människans förutsättningar och behov. Teknisk design med utgångspunkt och mål i god ergonomi innebär att exempelvis: Att designa produkter och utrustning som är enkla och tillförlitliga att använda med utgångspunkt i kunskap om kognitiv ergonomi, antropometri och belastningsergonomiska och biomekaniska analyserAtt designa säkra och effektiva tillverkningsprocesser med utgångspunkt i kunskap om kognitiv ergonomi och belastningsergonomiska analyserAtt designa organisationer utifrån kunskap om arbetslivsfysiologi och organisationsergonomiAtt designa arbetsuppgifter utifrån kunskap om kognitiv ergonomi, biomekanik och belastningsergonomiska analyserAtt designa enkla och användarvänliga gränssnitt med utgångspunkt i kognitiv ergonomiErgonomisk anpassning av en produkt eller en arbetsmiljö kan exempelvis handla om att se till att människan inte använder kroppen felaktigt. Det kan handla om fysisk belastning när en uppgift utförs, såväl som sensorisk input från olika system eller psykosocial belastning i form av stress. Det handlar om att utveckla kunskaper om människans begränsningar och förmågor, vilket ger bättre förutsättningar att bidra till användarvänliga lösningar. Det i sin tur bidrar till säkerhet och användarvänlighet och i slutändan att alla produkter, system och miljöer i vår omvärld fungerar väl för människan – det är hållbar utveckling om något. I kursen Ergonomi 2 vid civilingenjörsutbildningen Teknisk design, Luleå tekniska universitet, ingår en projektuppgift. Den syftar till att få fördjupad förståelse inom ergonomi genom att tillämpa kunskap och metoder i ett designprojekt för en verklig situation. Våren 2015 omfattade projektuppgiften att enanalys av valfri kontext, med syfte att förstå problem och utmaningar i den miljö, det sammanhang, den situation och för de personer som var berörda. Inledningsvis arbetade kursdeltagarna i grupper bestående av 3-4 personer, för att sedan gå in i en konceptutvecklingsfas individuellt. Det innebar att kursdeltagarna kunde genomföra ergonomiska analyser gemensamt och sedan utveckla konceptuella lösningar på egen hand. Det resulterade i att kursdeltagarna utvecklade tämligen olika lösningar, även om de haft en gemensam utgångspunkt. Bokens kapitel omfattar en beskrivning av respektive kontext följt av de konceptförslag som kursdeltagarna utvecklade. Som lärare är det alltid extra roligt när kursdeltagare är motiverade och engagerade inför projektuppgifter. Vår förhoppning är att det engagemanget ska framgå på följande sidor och att koncepten ska ge inspiration till att förbättra ergonomin i våra vardagsliv. Åsa Wikberg Nilsson, Therese Öhrling, Lars Sundström, Agneta Larsson och Ulrik RöijezonTeknisk design Luleå tekniska universitet, Augusti 2015
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| 3. |
- Berglund, Fanny, et al.
(författare)
-
An updated phylogeny of the metallo-β-lactamases.
- 2021
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Ingår i: The Journal of antimicrobial chemotherapy. - : Oxford University Press (OUP). - 1460-2091 .- 0305-7453. ; 76:1, s. 117-123
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Tidskriftsartikel (refereegranskat)abstract
- Metallo-β-lactamases (MBLs) are enzymes that use zinc-dependent hydrolysis to confer resistance to almost all available β-lactam antibiotics. They are hypothesized to originate from commensal and environmental bacteria, from where some have mobilized and transferred horizontally to pathogens. The current phylogeny of MBLs, however, is biased as it is founded largely on genes encountered in pathogenic bacteria. This incompleteness is emphasized by recent findings of environmental MBLs with new forms of zinc binding sites and atypical functional profiles.To expand the phylogeny of MBLs to provide a more accurate view of their evolutionary history.We searched more than 16 terabases of genomic and metagenomic data for MBLs of the three subclasses B1, B2 and B3 using the validated fARGene method. Predicted genes, together with the previously known ones, were used to infer phylogenetic trees.We identified 2290 unique MBL genes forming 817 gene families, of which 741 were previously uncharacterized. MBLs from subclasses B1 and B3 separated into distinct monophyletic groups, in agreement with their taxonomic and functional properties. We present evidence that clinically associated MBLs were mobilized from Proteobacteria. Additionally, we identified three new variants of the zinc binding sites, indicating that the functional repertoire is broader than previously reported.Based on our results, we recommend that the nomenclature of MBLs is refined into the phylogenetic groups B1.1-B1.5 and B3.1-B3.4 that more accurately describe their molecular and functional characteristics. Our results will also facilitate the annotation of novel MBLs, reflecting their taxonomic organization and evolutionary origin.
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| 4. |
- Berglund, Fanny, et al.
(författare)
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Comprehensive screening of genomic and metagenomic data reveals a large diversity of tetracycline resistance genes
- 2020
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Ingår i: Microbial genomics. - : Microbiology Society. - 2057-5858. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- Tetracyclines are broad-spectrum antibiotics used to prevent or treat a variety of bacterial infections. Resistance is often mediated through mobile resistance genes, which encode one of the three main mechanisms: active efflux, ribosomal target protection or enzymatic degradation. In the last few decades, a large number of new tetracycline-resistance genes have been discovered in clinical settings. These genes are hypothesized to originate from environmental and commensal bacteria, but the diversity of tetracycline-resistance determinants that have not yet been mobilized into pathogens is unknown. In this study, we aimed to characterize the potential tetracycline resistome by screening genomic and metagenomic data for novel resistance genes. By using probabilistic models, we predicted 1254 unique putative tetracycline resistance genes, representing 195 gene families (<70% amino acid sequence identity), whereof 164 families had not been described previously. Out of 17 predicted genes selected for experimental verification, 7 induced a resistance phenotype in an Escherichia coli host. Several of the predicted genes were located on mobile genetic elements or in regions that indicated mobility, suggesting that they easily can be shared between bacteria. Furthermore, phylogenetic analysis indicated several events of horizontal gene transfer between bacterial phyla. Our results also suggested that acquired efflux pumps originate from proteobacterial species, while ribosomal protection genes have been mobilized from Firmicutes and Actinobacteria. This study significantly expands the knowledge of known and putatively novel tetracycline resistance genes, their mobility and evolutionary history. The study also provides insights into the unknown resistome and genes that may be encountered in clinical settings in the future.
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| 5. |
- Berglund, Fanny, et al.
(författare)
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Dietary habits among snus users : a population-based cross-sectional study
- 2023
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Ingår i: Food & Nutrition Research. - : SNF Swedish Nutrition Foundation. - 1654-6628 .- 1654-661X. ; 67
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Tidskriftsartikel (refereegranskat)abstract
- Background: The dietary habits among snus users are largely unknown and have not been accounted for in observational studies on the health effects of snus use.Aim: To examine whether snus users eat unhealthier than never tobacco users.Methods: A total of 3,397 male participants, examined between 1994 and 2014 in the Northern Sweden Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study, were included. Snus use and dietary habits were self-reported using questionnaires, from which intakes of different food groups, macronutrients, and a healthy diet score (HDS) were calculated (the latter as a proxy for overall diet quality). The association between snus use and dietary habits was examined by quantile regression models.Results: In the multivariable-adjusted model, current snus users had a lower HDS (median difference: -0.86 [95% confidence interval: -1.32, -0.40]) than never tobacco users. Snus users also consumed fewer weekly servings of fruits and berries (median difference: -1.03 [-1.65, -0.40]), and their estimated percentage of energy intake con -sisted of less carbohydrates (median difference: -1.43 [-2.12, -0.74]) and of more total fat (median difference: 0.99 [0.30, 1.67]), saturated fat (median difference: 0.67 [0.29, 1.05]), monounsaturated fat (median difference: 0.44 [0.20, 0.68]), trans fat (median difference: 0.03 [0.01, 0.06]), and alcohol (median difference: 0.21 [0.02, 0.40]).Conclusion: We observed that snus users had an unhealthier diet than never tobacco users. Future studies on the association between snus use and health outcomes should, therefore, consider diet as a potential confounder.
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| 6. |
- Berglund, Fanny, et al.
(författare)
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Evidence for wastewaters as environments where mobile antibiotic resistance genes emerge
- 2023
-
Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- The emergence and spread of mobile antibiotic resistance genes (ARGs) in pathogens have become a serious threat to global health. Still little is known about where ARGs gain mobility in the first place. Here, we aimed to collect evidence indicating where suchinitial mobilizationevents of clinically relevant ARGs may have occurred. We found that the majority of previously identified origin species did not carry the mobilizing elements that likely enabled intracellular mobility of the ARGs, suggesting a necessary interplay between different bacteria. Analyses of a broad range of metagenomes revealed that wastewaters and wastewater-impacted environments had by far the highest abundance of both origin species and corresponding mobilizing elements. Most origin species were only occasionally detected in other environments. Co-occurrence of origin species and corresponding mobilizing elements were rare in human microbiota. Our results identify wastewaters and wastewater-impacted environments as plausible arenas for the initial mobilization of resistance genes.
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| 7. |
- Berglund, Fanny, 1988, et al.
(författare)
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Identification and reconstruction of novel antibiotic resistance genes from metagenomes
- 2019
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Ingår i: Microbiome. - : Springer Science and Business Media LLC. - 2049-2618. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundEnvironmental and commensal bacteria maintain a diverse and largely unknown collection of antibiotic resistance genes (ARGs) that, over time, may be mobilized and transferred to pathogens. Metagenomics enables cultivation-independent characterization of bacterial communities but the resulting data is noisy and highly fragmented, severely hampering the identification of previously undescribed ARGs. We have therefore developed fARGene, a method for identification and reconstruction of ARGs directly from shotgun metagenomic data.ResultsfARGene uses optimized gene models and can therefore with high accuracy identify previously uncharacterized resistance genes, even if their sequence similarity to known ARGs is low. By performing the analysis directly on the metagenomic fragments, fARGene also circumvents the need for a high-quality assembly. To demonstrate the applicability of fARGene, we reconstructed -lactamases from five billion metagenomic reads, resulting in 221 ARGs, of which 58 were previously not reported. Based on 38 ARGs reconstructed by fARGene, experimental verification showed that 81% provided a resistance phenotype in Escherichia coli. Compared to other methods for detecting ARGs in metagenomic data, fARGene has superior sensitivity and the ability to reconstruct previously unknown genes directly from the sequence reads.ConclusionsWe conclude that fARGene provides an efficient and reliable way to explore the unknown resistome in bacterial communities. The method is applicable to any type of ARGs and is freely available via GitHub under the MIT license.
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| 8. |
- Berglund, Fanny, 1988, et al.
(författare)
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Identification of 76 novel B1 metallo-beta-lactamases through large-scale screening of genomic and metagenomic data
- 2017
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Ingår i: Microbiome. - : Springer Science and Business Media LLC. - 2049-2618. ; 5:1, s. 134-134
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Tidskriftsartikel (refereegranskat)abstract
- Background: Metallo-beta-lactamases are bacterial enzymes that provide resistance to carbapenems, the most potent class of antibiotics. These enzymes are commonly encoded on mobile genetic elements, which, together with their broad substrate spectrum and lack of clinically useful inhibitors, make them a particularly problematic class of antibiotic resistance determinants. We hypothesized that there is a large and unexplored reservoir of unknown metallo-beta-lactamases, some of which may spread to pathogens, thereby threatening public health. The aim of this study was to identify novel metallo-beta-lactamases of class B1, the most clinically important subclass of these enzymes. Results: Based on a new computational method using an optimized hidden Markov model, we analyzed over 10,000 bacterial genomes and plasmids together with more than 5 terabases of metagenomic data to identify novel metallo-beta-lactamase genes. In total, 76 novel genes were predicted, forming 59 previously undescribed metallo-beta-lactamase gene families. The ability to hydrolyze imipenem in an Escherichia coli host was experimentally confirmed for 18 of the 21 tested genes. Two of the novel B1 metallo-beta-lactamase genes contained atypical zinc-binding motifs in their active sites, which were previously undescribed for metallo-beta-lactamases. Phylogenetic analysis showed that B1 metallo-beta-lactamases could be divided into five major groups based on their evolutionary origin. Our results also show that, except for one, all of the previously characterized mobile B1 beta-lactamases are likely to have originated from chromosomal genes present in Shewanella spp. and other Proteobacterial species. Conclusions: This study more than doubles the number of known B1 metallo-beta-lactamases. The findings have further elucidated the diversity and evolutionary history of this important class of antibiotic resistance genes and prepare us for some of the challenges that may be faced in clinics in the future.
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| 9. |
- Berglund, Fanny
(författare)
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Identification of novel antibiotic resistance genes through large-scale data analysis
- 2017
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Antibiotic resistance is increasing worldwide, and is considered a serious threat to public health by e.g. the World Health Organization. Antibiotic resistance genes are hypothesized to originate from harmless bacteria in and around us, from where they are horizontally transfered into human pathogens. It is therefore of great importance to explore human-associated and environmental bacterial communities to identify novel antibiotic resistance genes before they reach clinical settings. The three papers presented in this thesis aim to identify novel antibiotic resistance genes in large genomic and metagenomic datasets. In paper I, the aim was to identify novel genes of the clinically important subclass B1 metallo-β-lactamases. By analyzing whole bacterial genomes as well as metagenomes from environmental and human-associated bacterial communities, 76 novel putative B1 genes were predicted. Twenty-one of these were selected for experimental validation, whereof 18 expressed the predicted phenotype in E. coli. Phylogentic analysis revealed that the novel genes formed 59 previously undescribed gene families. In paper II, a large volume of genomic and metagenomic data was searched for novel plasmid-mediated quinolone resistance (qnr ) genes. In total, 611 qnr genes were predicted, of which 20 were putative novel. Nine of these were experimentally tested in E. coli, whereof eight expressed the predicted phenotype. In paper III, a new method for identification and reconstruction of novel antibiotic resistance genes from fragmented metagenomic data was presented. The method is based on gene specific models, which are optimized for a high sensitivity and specificity. The method is furthermore computationally efficient and can be applied to any class of resistance genes. The results of this thesis provides a deeper insight to the diversity and evolutionary history of two types of clinically relevant antibiotic resistance genes. It also provides new methods for efficient and reliable identification of novel resistance genes in fragmented metagenomic data.
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| 10. |
- Berglund, Fanny, 1988
(författare)
-
New antibiotic resistance genes and their diversity
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Antibiotic resistance is increasing worldwide and is considered a severe threat to public health. Often, antibiotic resistance is caused by antibiotic resistance genes, of which many are hypothesized to have been transferred into human pathogens from environmental bacteria. It is, therefore, of great importance to explore bacterial communities to identify new antibiotic resistance genes before they reach clinical settings. The six papers presented in this thesis aim to identify new antibiotic resistance genes in large genomic and metagenomic datasets and to place them in an evolutionary context. In Paper I, a new method for the identification and reconstruction of new antibiotic resistance genes directly from fragmented metagenomic data was developed and was shown to outperform other methods significantly. In Papers II and III, novel genes of the clinically important class metallo-β-lactamases were identified. By analyzing metagenomes and bacterial genomes, 96 novel putative metallo-β-lactamase genes were predicted. In Paper IV, the diversity and phylogeny of the metallo-β-lactamases were further investigated. The results showed that the genes mainly clustered based on the taxonomy of the host species and that many of the mobile metallo-β-lactamases potentially were mobilized from species of the phylum Proteobacteria. In Paper V, the aim was to identify new genes providing resistance to the antibiotic class tetracyclines. A total of 195 gene families were predicted, of which 164 were new putative tetracycline resistance genes. Finally, in Paper VI, we searched for and predicted 20 novel putative quinolone resistance (qnr) genes from a large amount of metagenomic data. Throughout the thesis, a total of 54 novel genes have been functionally verified in Escherichia coli, of which 37 expressed the predicted phenotype. The results of this thesis provide deeper insights into the diversity and evolutionary history of three major classes of antibiotic resistance genes. It also provides new methodologies for efficient and reliable identification of new resistance genes in genomic and metagenomic data.
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| 11. |
- Berglund, Fanny, et al.
(författare)
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The resistome and microbiome of wastewater treatment plant workers - The AWARE study.
- 2023
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Ingår i: Environment international. - 0160-4120 .- 1873-6750. ; 180
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Tidskriftsartikel (refereegranskat)abstract
- Urban wastewater treatment plants harbor a large collection of antibiotic resistant enteric bacteria. It is therefore reasonable to hypothesize that workers at such plants would possess a more diverse set of resistant enteric bacteria, compared to the general population. To address this hypothesis, we have compared the fecal microbiome and resistome of 87 workers at wastewater treatment plants (WWTPs) from Romania and the Netherlands to those of 87 control individuals, using shotgun metagenomics. Controlling for potential confounders, neither the total antibiotic resistance gene (ARG) abundance, nor the overall bacterial composition were significantly different between the two groups. If anything, the ARG richness was slightly lower in WWTP workers, and in a stratified analysis the total ARG abundance was significantly lower in Dutch workers compared to Dutch control participants. We identified country of residence, together with recent antibiotic intake in the Dutch population, as the largest contributing factors to the total abundance of ARGs. A striking side-finding was that sex was associated with carriage of disinfectant resistance genes, with women in both Romania and the Netherlands having significantly higher abundance compared to men. A follow up investigation including an additional 313 publicly available samples from healthy individuals from three additional countries showed that the difference was significant for three genes conferring resistance to chemicals commonly used in cosmetics and cleaning products. We therefore hypothesize that the use of cosmetics and, possibly, cleaning products leads to higher abundance of disinfectant resistance genes in the microbiome of the users. Altogether, this study shows that working at a WWTP does not lead to a higher abundance or diversity of ARGs and no large shifts in the overall gut microbial composition in comparison to participants not working at a WWTP. Instead, other factors such as country of residence, recent antibiotic intake and sex seem to play a larger role.
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| 12. |
- 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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| 13. |
- Ebmeyer, Stefan, 1990, et al.
(författare)
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GEnView: a gene-centric, phylogeny-based comparative genomics pipeline for bacterial genomes and plasmids
- 2022
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 38:6, s. 1727-1728
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Tidskriftsartikel (refereegranskat)abstract
- Comparing genomic loci of a given bacterial gene across strains and species can provide insights into their evolution, including information on e.g. acquired mobility, the degree of conservation between different taxa or indications of horizontal gene transfer events. While thousands of bacterial genomes are available to date, there is no software that facilitates comparisons of individual gene loci for a large number of genomes. GEnView (Genetic Environment View) is a Python-based pipeline for the comparative analysis of gene-loci in a large number of bacterial genomes, providing users with automated, taxon-selective access to the >800.000 genomes and plasmids currently available in the NCBI Assembly and RefSeq databases, and is able to process local genomes that are not deposited at NCBI, enabling searches for genomic sequences and to analyze their genetic environments through the interactive visualization and extensive metadata files created by GEnView.
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| 14. |
- Fredriksson, Fanny, 1985-, et al.
(författare)
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Sutures impregnated with carbazate-activated polyvinyl alcohol reduce intraperitoneal adhesions
- 2017
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Ingår i: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468 .- 1531-5037. ; 52:11, s. 1853-1858
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intraperitoneal adhesions cause significant morbidity. They occur after peritoneal trauma, which induces oxidative stress with production of inflammatory cytokines, peroxidized proteins (carbonyls) and lipids (aldehydes). This study aimed to investigate if carbazate-activated polyvinyl alcohol (PVAC), an aldehyde-carbonyl inhibitor, can reduce intraperitoneal adhesions in an experimental model.Material and methods: Male Sprague-Dawley rats (n = 110) underwent laparotomy, cecal abrasion and construction of a small bowel anastomosis. They either were treated with intraperitoneal instillation of PVAC or were sutured with PVAC-impregnated sutures. Thromboelastography analysis was performed using human blood and PVAC. The lipid peroxidation product malondialdehyde (MDA) and inflammatory cytokines IL-1 beta and IL-6 were quantified in peritoneal fluid. At day 7, bursting pressure of the anastomosis was measured and adhesions were blindly scored.Results: PVAC in human blood decreased the production of the fibrin-thrombocyte mesh without affecting the coagulation cascade. MDA, IL-1 beta and IL-6 were increased after 6 h without significant difference between the groups. PVAC-impregnated sutures reduced intraperitoneal adhesions compared to controls (p = 0.0406) while intraperitoneal instillation of PVAC had no effect. Anastomotic bursting pressure was unchanged.Conclusions: Intervention with an aldehyde-carbonyl inhibitor locally in the wound by PVAC-impregnated sutures might be a new strategy to reduce intraperitoneal adhesions.
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| 15. |
- Fröhlich, Christopher, et al.
(författare)
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Structural and biochemical characterization of the environmental MBLs MYO-1, ECV-1 and SHD-1.
- 2020
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Ingår i: The Journal of antimicrobial chemotherapy. - : Oxford University Press (OUP). - 1460-2091 .- 0305-7453. ; 75:9, s. 2554-2563
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Tidskriftsartikel (refereegranskat)abstract
- MBLs form a large and heterogeneous group of bacterial enzymes conferring resistance to β-lactam antibiotics, including carbapenems. A large environmental reservoir of MBLs has been identified, which can act as a source for transfer into human pathogens. Therefore, structural investigation of environmental and clinically rare MBLs can give new insights into structure-activity relationships to explore the role of catalytic and second shell residues, which are under selective pressure.To investigate the structure and activity of the environmental subclass B1 MBLs MYO-1, SHD-1 and ECV-1.The respective genes of these MBLs were cloned into vectors and expressed in Escherichia coli. Purified enzymes were characterized with respect to their catalytic efficiency (kcat/Km). The enzymatic activities and MICs were determined for a panel of different β-lactams, including penicillins, cephalosporins and carbapenems. Thermostability was measured and structures were solved using X-ray crystallography (MYO-1 and ECV-1) or generated by homology modelling (SHD-1).Expression of the environmental MBLs in E. coli resulted in the characteristic MBL profile, not affecting aztreonam susceptibility and decreasing susceptibility to carbapenems, cephalosporins and penicillins. The purified enzymes showed variable catalytic activity in the order of <5% to ∼70% compared with the clinically widespread NDM-1. The thermostability of ECV-1 and SHD-1 was up to 8°C higher than that of MYO-1 and NDM-1. Using solved structures and molecular modelling, we identified differences in their second shell composition, possibly responsible for their relatively low hydrolytic activity.These results show the importance of environmental species acting as reservoirs for MBL-encoding genes.
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| 16. |
- Gustavsson, Kristian, 1980, et al.
(författare)
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Preferential Sampling and Small-Scale Clustering of Gyrotactic Microswimmers in Turbulence
- 2016
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 116:10
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies show that spherical motile microorganisms in turbulence subject to gravitational torques gather in down-welling regions of the turbulent flow. By analyzing a statistical model we analytically compute how shape affects the dynamics, preferential sampling, and small-scale spatial clustering. We find that oblong organisms may spend more time in up-welling regions of the flow, and that all organisms are biased to regions of positive fluid-velocity gradients in the upward direction. We analyze small-scale spatial clustering and find that oblong particles may either cluster more or less than spherical ones, depending on the strength of the gravitational torques. © 2016 American Physical Society.
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| 17. |
- Karkman, Antti, et al.
(författare)
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Predicting clinical resistance prevalence using sewage metagenomic data
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- © 2020, The Author(s). Antibiotic resistance surveillance through regional and up-to-date testing of clinical isolates is a foundation for implementing effective empirical treatment. Surveillance data also provides an overview of geographical and temporal changes that are invaluable for guiding interventions. Still, due to limited infrastructure and resources, clinical surveillance data is lacking in many parts of the world. Given that sewage is largely made up of human fecal bacteria from many people, sewage epidemiology could provide a cost-efficient strategy to partly fill the current gap in clinical surveillance of antibiotic resistance. Here we explored the potential of sewage metagenomic data to assess clinical antibiotic resistance prevalence using environmental and clinical surveillance data from across the world. The sewage resistome correlated to clinical surveillance data of invasive Escherichia coli isolates, but none of several tested approaches provided a sufficient resolution for clear discrimination between resistance towards different classes of antibiotics. However, in combination with socioeconomic data, the overall clinical resistance situation could be predicted with good precision. We conclude that analyses of bacterial genes in sewage could contribute to informing management of antibiotic resistance.
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| 18. |
- Lund, David, 1994, et al.
(författare)
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Extensive screening reveals previously undiscovered aminoglycoside resistance genes in human pathogens
- 2023
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Ingår i: Communications Biology. - 2399-3642. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Antibiotic resistance is a growing threat to human health, caused in part by pathogens accumulating antibiotic resistance genes (ARGs) through horizontal gene transfer. New ARGs are typically not recognized until they have become widely disseminated, which limits our ability to reduce their spread. In this study, we use large-scale computational screening of bacterial genomes to identify previously undiscovered mobile ARGs in pathogens. From ~1 million genomes, we predict 1,071,815 genes encoding 34,053 unique aminoglycoside-modifying enzymes (AMEs). These cluster into 7,612 families (<70% amino acid identity) of which 88 are previously described. Fifty new AME families are associated with mobile genetic elements and pathogenic hosts. From these, 24 of 28 experimentally tested AMEs confer resistance to aminoglycoside(s) in Escherichia coli, with 17 providing resistance above clinical breakpoints. This study greatly expands the range of clinically relevant aminoglycoside resistance determinants and demonstrates that computational methods enable early discovery of potentially emerging ARGs.
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| 19. |
- Lund, David, 1994, et al.
(författare)
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Large-scale characterization of the macrolide resistome reveals high diversity and several new pathogen-associated genes
- 2022
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Ingår i: Microbial Genomics. - : Microbiology Society. - 2057-5858. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Macrolides are broad-spectrum antibiotics used to treat a range of infections. Resistance to macrolides is often conferred by mobile resistance genes encoding Erm methyltransferases or Mph phosphotransferases. New erm and mph genes keep being discovered in clinical settings but their origins remain unknown, as is the type of macrolide resistance genes that will appear in the future. In this study, we used optimized hidden Markov models to characterize the macrolide resistome. Over 16 terabases of genomic and metagenomic data, representing a large taxonomic diversity (11 030 species) and diverse environments (1944 metagenomic samples), were searched for the presence of erm and mph genes. From this data, we predicted 28 340 macrolide resistance genes encoding 2892 unique protein sequences, which were clustered into 663 gene families (<70 % amino acid identity), of which 619 (94 %) were previously uncharacterized. This included six new resistance gene families, which were located on mobile genetic elements in pathogens. The function of ten predicted new resistance genes were experimentally validated in Escherichia coli using a growth assay. Among the ten tested genes, seven conferred increased resistance to erythromycin, with five genes additionally conferring increased resistance to azithromycin, showing that our models can be used to predict new functional resistance genes. Our analysis also showed that macrolide resistance genes have diverse origins and have transferred horizontally over large phylogenetic distances into human pathogens. This study expands the known macrolide resistome more than ten-fold, provides insights into its evolution, and demonstrates how computational screening can identify new resistance genes before they become a significant clinical problem.
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| 20. |
- Marathe, Nachiket, et al.
(författare)
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Functional metagenomics reveals a novel carbapenem-hydrolyzing mobile beta-lactamase from Indian river sediments contaminated with antibiotic production waste
- 2018
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 112, s. 279-286
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 Elsevier Ltd Evolution has provided environmental bacteria with a plethora of genes that give resistance to antibiotic compounds. Under anthropogenic selection pressures, some of these genes are believed to be recruited over time into pathogens by horizontal gene transfer. River sediment polluted with fluoroquinolones and other drugs discharged from bulk drug production in India constitute an environment with unprecedented, long-term antibiotic selection pressures. It is therefore plausible that previously unknown resistance genes have evolved and/or are promoted here. In order to search for novel resistance genes, we therefore analyzed such river sediments by a functional metagenomics approach. DNA fragments providing resistance to different antibiotics in E. coli were sequenced using Sanger and PacBio RSII platforms. We recaptured the majority of known antibiotic resistance genes previously identified by open shot-gun metagenomics sequencing of the same samples. In addition, seven novel resistance gene candidates (six beta-lactamases and one amikacin resistance gene) were identified. Two class A beta-lactamases, bla RSA1 and bla RSA2 , were phylogenetically close to clinically important ESBLs like bla GES , bla BEL and bla L2 , and were further characterized for their substrate spectra. The blaRSA1 protein, encoded as an integron gene cassette, efficiently hydrolysed penicillins, first generation cephalosporins and cefotaxime, while blaRSA2 was an inducible class A beta-lactamase, capable of hydrolyzing carbapenems albeit with limited efficiency, similar to the L2 beta-lactamase from Stenotrophomonas maltophilia. All detected novel genes were associated with plasmid mobilization proteins, integrons, and/or other resistance genes, suggesting a potential for mobility. This study provides insight into a resistome shaped by an exceptionally strong and long-term antibiotic selection pressure. An improved knowledge of mobilized resistance factors in the external environment may make us better prepared for the resistance challenges that we may face in clinics in the future.
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| 21. |
- Marathe, Nachiket, et al.
(författare)
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Sewage effluent from an Indian hospital harbors novel carbapenemases and integron-borne antibiotic resistance genes
- 2019
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Ingår i: Microbiome. - : Springer Science and Business Media LLC. - 2049-2618. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hospital wastewaters contain fecal material from a large number of individuals, of which many are undergoing antibiotic therapy. It is, thus, plausible that hospital wastewaters could provide opportunities to find novel carbapenemases and other resistance genes not yet described in clinical strains. Our aim was therefore to investigate the microbiota and antibiotic resistome of hospital effluent collected from the city of Mumbai, India, with a special focus on identifying novel carbapenemases. Results: Shotgun metagenomics revealed a total of 112 different mobile antibiotic resistance gene types, conferring resistance against almost all classes of antibiotics. Beta-lactamase genes, including encoding clinically important carbapenemases, such as NDM, VIM, IMP, KPC, and OXA-48, were abundant. NDM (0.9% relative abundance to 16S rRNA genes) was the most common carbapenemase gene, followed by OXA-58 (0.84% relative abundance to 16S rRNA genes). Among the investigated mobile genetic elements, class 1 integrons (11% relative abundance to 16S rRNA genes) were the most abundant. The genus Acinetobacter accounted for as many as 30% of the total 16S rRNA reads, with A. baumannii accounting for an estimated 2.5%. High throughput sequencing of amplified integron gene cassettes identified a novel functional variant of an IMP-type (proposed IMP-81) carbapenemase gene (eight aa substitutions) along with recently described novel resistance genes like sul4 and bla RSA1. Using a computational hidden Markov model, we detected 27 unique metallo-beta-lactamase (MBL) genes in the shotgun data, of which nine were novel subclass B1 genes, one novel subclass B2, and 10 novel subclass B3 genes. Six of the seven novel MBL genes were functional when expressed in Escherichia coli. Conclusion: By exploring hospital wastewater from India, our understanding of the diversity of carbapenemases has been extended. The study also demonstrates that the microbiota of hospital wastewater can serve as a reservoir of novel resistance genes, including previously uncharacterized carbapenemases with the potential to spread further.
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| 22. |
- Marutescu, L. G., et al.
(författare)
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Wastewater treatment plants, an "escape gate" for ESCAPE pathogens
- 2023
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Ingår i: Frontiers in Microbiology. - 1664-302X. ; 14
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Forskningsöversikt (refereegranskat)abstract
- Antibiotics are an essential tool of modern medicine, contributing to significantly decreasing mortality and morbidity rates from infectious diseases. However, persistent misuse of these drugs has accelerated the evolution of antibiotic resistance, negatively impacting clinical practice. The environment contributes to both the evolution and transmission of resistance. From all anthropically polluted aquatic environments, wastewater treatment plants (WWTPs) are probably the main reservoirs of resistant pathogens. They should be regarded as critical control points for preventing or reducing the release of antibiotics, antibiotic-resistant bacteria (ARB), and antibiotic-resistance genes (ARGs) into the natural environment. This review focuses on the fate of the pathogens Enterococcus faecium, Staphylococcus aureus, Clostridium difficile, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae spp. (ESCAPE) in WWTPs. All ESCAPE pathogen species, including high-risk clones and resistance determinants to last-resort antibiotics such as carbapenems, colistin, and multi-drug resistance platforms, were detected in wastewater. The whole genome sequencing studies demonstrate the clonal relationships and dissemination of Gram-negative ESCAPE species into the wastewater via hospital effluents and the enrichment of virulence and resistance determinants of S. aureus and enterococci in WWTPs. Therefore, the efficiency of different wastewater treatment processes regarding the removal of clinically relevant ARB species and ARGs, as well as the influence of water quality factors on their performance, should be explored and monitored, along with the development of more effective treatments and appropriate indicators (ESCAPE bacteria and/or ARGs). This knowledge will allow the development of quality standards for point sources and effluents to consolidate the WWTP barrier role against the environmental and public health AR threats.
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| 23. |
- Munk, P., et al.
(författare)
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Genomic analysis of sewage from 101 countries reveals global landscape of antimicrobial resistance
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance (AMR) is a major threat to global health. Understanding the emergence, evolution, and transmission of individual antibiotic resistance genes (ARGs) is essential to develop sustainable strategies combatting this threat. Here, we use metagenomic sequencing to analyse ARGs in 757 sewage samples from 243 cities in 101 countries, collected from 2016 to 2019. We find regional patterns in resistomes, and these differ between subsets corresponding to drug classes and are partly driven by taxonomic variation. The genetic environments of 49 common ARGs are highly diverse, with most common ARGs carried by multiple distinct genomic contexts globally and sometimes on plasmids. Analysis of flanking sequence revealed ARG-specific patterns of dispersal limitation and global transmission. Our data furthermore suggest certain geographies are more prone to transmission events and should receive additional attention.
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| 24. |
- Rodriguez-Molina, D., et al.
(författare)
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Carriage of ESBL-producing Enterobacterales in wastewater treatment plant workers and surrounding residents - the AWARE Study
- 2021
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Ingår i: European Journal of Clinical Microbiology & Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373.
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Tidskriftsartikel (refereegranskat)abstract
- To investigate whether wastewater treatment plant (WWTP) workers and residents living in close proximity to a WWTP have elevated carriage rates of ESBL-producing Enterobacterales, as compared to the general population. From 2018 to 2020, we carried out a cross-sectional study in Germany, the Netherlands, and Romania among WWTP workers (N = 344), nearby residents (living <= 300 m away from WWTPs; N = 431) and distant residents (living >= 1000 m away = reference group; N = 1165). We collected information on potential confounders via questionnaire. Culture of participants' stool samples was performed with ChromID (R)-ESBL agar plates and species identification with MALDI-TOF-MS. We used logistic regression to estimate the odds ratio (OR) for carrying ESBL-producing E. coli (ESBL-EC). Sensitivity analyses included stratification by country and interaction models using country as secondary exposure. Prevalence of ESBL-EC was 11% (workers), 29% (nearby residents), and 7% (distant residents), and higher in Romania (28%) than in Germany (7%) and the Netherlands (6%). Models stratified by country showed that within the Romanian population, WWTP workers are about twice as likely (aOR = 2.34, 95% CI: 1.22-4.50) and nearby residents about three times as likely (aOR = 3.17, 95% CI: 1.80-5.59) to be ESBL-EC carriers, when compared with distant residents. In stratified analyses by country, we found an increased risk for carriage of ESBL-EC in Romanian workers and nearby residents. This effect was higher for nearby residents than for workers, which suggests that, for nearby residents, factors other than the local WWTP could contribute to the increased carriage.
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| 25. |
- Rodriguez-Molina, D., et al.
(författare)
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International Travel as a Risk Factor for Carriage of Extended-Spectrum beta-Lactamase-Producing Escherichia coli in a Large Sample of European Individuals-The AWARE Study
- 2022
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Ingår i: INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH. - : MDPI AG. - 1660-4601. ; 19:8
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Tidskriftsartikel (refereegranskat)abstract
- Antibiotic resistance (AR) is currently a major threat to global health, calling for a One Health approach to be properly understood, monitored, tackled, and managed. Potential risk factors for AR are often studied in specific high-risk populations, but are still poorly understood in the general population. Our aim was to explore, describe, and characterize potential risk factors for carriage of Extended-Spectrum Beta-Lactamase-resistant Escherichia coli (ESBL-EC) in a large sample of European individuals aged between 16 and 67 years recruited from the general population in Southern Germany, the Netherlands, and Romania. Questionnaire and stool sample collection for this cross-sectional study took place from September 2018 to March 2020. Selected cultures of participants' stool samples were analyzed for detection of ESBL-EC. A total of 1183 participants were included in the analyses: 333 from Germany, 689 from the Netherlands, and 161 from Romania. Travels to Northern Africa (adjusted Odds Ratio, aOR 4.03, 95% Confidence Interval, CI 1.67-9.68), Sub-Saharan Africa (aOR 4.60, 95% CI 1.60-13.26), and Asia (aOR 4.08, 95% CI 1.97-8.43) were identified as independent risk factors for carriage of ESBL-EC. Therefore, travel to these regions should continue to be routinely asked about by clinical practitioners as possible risk factors when considering antibiotic therapy.
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