Publikasjoner
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Rued, Britta E.; Dhariwal, Achal; Covington, Brett C.; Seyedsayamdost, Mohammad R.; Krivograd, Sophie A. & Pesavento, Russell P.
[Vis alle 8 forfattere av denne artikkelen]
(2025).
Impact of the RaS-RiPP tryglysin and culturing conditions on ex-vivo oral microbiomes.
npj Biofilms and Microbiomes.
11(1).
doi:
10.1038/s41522-025-00794-8.
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Abstract Natural products are ubiquitously produced by many species that we encounter during our daily lives. One genus, Streptococcus , can produce a wide array of quorum sensing linked natural products known as RaS-RiPPs (ribosomally synthesized and post-translationally modified peptides). Their production is triggered by the induction of an Rgg-SHP quorum sensing system, which senses the presence of SHPs (short hydrophobic peptides) and induces the gene expression of these operons. Previous work has found that streptococcal RaS-RiPPs modulate the growth of different streptococci and might play a role in antibiotic tolerance. This is of particular importance to the oral microbiome, where streptococci are a predominant genus. This study provides the first report on attempts to study the impact of the RaS-RiPP Tryglysin A on ex-vivo oral systems and explores important factors to consider when culturing these systems. We explore how medium selection, atmosphere, growth model, and saliva amount can impact the presence of both bacterial and fungal species. These studies provide the groundwork for determining how RaS-RiPP producing Streptococci might impact the composition and function of oral microbiome communities, as well as important aspects to consider when culturing ex-vivo oral systems.
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Farooq, Samiya; Talat, Absar; Dhariwal, Achal; Petersen, Fernanda Cristina & Khan, Asad U.
(2025).
Transgenerational gut dysbiosis: Unveiling the dynamics of antibiotic resistance through mobile genetic elements from mothers to infants.
International Journal of Antimicrobial Agents.
ISSN 0924-8579.
65(5).
doi:
10.1016/j.ijantimicag.2025.107458.
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Shawrob, Kazi Shefaul Mulk; Dhariwal, Achal; Salvadori, Gabriela; Gladstone, Rebecca Ashley & Junges, Roger
(2025).
Large-scale global molecular epidemiology of antibiotic resistance determinants in Streptococcus pneumoniae.
Microbial Genomics.
11(7).
doi:
10.1099/mgen.0.001444.
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Streptococcus pneumoniae is a leading pathogen in terms of deaths attributable to or associated with antimicrobial resistance globally. Thus, monitoring antibiotic resistance determinants constitutes a key aspect of surveillance efforts for this microbe. Leveraging publicly available whole-genome sequencing (WGS) data, we aimed to investigate the presence and distribution patterns of antibiotic resistance determinants in S. pneumoniae with a focus on multidrug resistance (MDR) and serotype distribution. Metadata and genomes were obtained from the National Center for Biotechnology Information Pathogen Detection database. Curation and harmonization were performed in R and SPSS. Data on resistance patterns were defined according to AMRFinderPlus, and a combination of prediction tools was employed for in silico serotyping. Analyses involved 75,161 genomes totalling 122,673 gene/allele counts from 14 antibiotic classes. MDR was observed in 16.7% of isolates, with the highest increasing rates in Asia and South America. Within antibiotic classes, an increase in macrolide resistance genes was highlighted, particularly in the proportion of genomes presenting mef(A)/msr(D). Over a third of isolates with serotypes 19F, 23F, 15A, 6B and 19A showed MDR. We further observed the highest significant increases in the presence of resistance in 33F, 22F, 10A and 23A. Serotype 13, not included in any vaccine formulation, presented high MDR rates with a strong increasing trend. The findings of this study highlight variations in resistance determinants globally and across serotypes over time. Collectively, these data underscore the added value of utilizing public WGS data to investigate the effectiveness and repercussions of treatment and vaccination strategies on managing antibiotic resistance.
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Dhariwal, Achal; Shekhar, Sudhanshu & Petersen, Fernanda Cristina
(2025).
Nasal microbiota transplantation: a gateway to novel treatments.
Trends in Microbiology.
ISSN 0966-842X.
doi:
10.1016/j.tim.2024.12.010.
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Two recent studies have highlighted the potential of nasal microbiota transplantation (NMT) to treat chronic rhinosinusitis (CRS). Here we evaluate these findings and propose that lessons from fecal microbiota transplantation (FMT) could guide NMT development, with possible implications for combating antimicrobial resistance in respiratory infections.
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Brar, Navdeep Kaur; Dhariwal, Achal; Shekhar, Sudhanshu; Junges, Roger; Hakansson, Anders P. & Petersen, Fernanda Cristina
(2024).
HAMLET, a human milk protein-lipid complex, modulates amoxicillin induced changes in an ex vivo biofilm model of the oral microbiome.
Frontiers in Microbiology.
15.
doi:
10.3389/fmicb.2024.1406190.
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Challenges from infections caused by biofilms and antimicrobial resistance highlight the need for novel antimicrobials that work in conjunction with antibiotics and minimize resistance risk. In this study we investigated the composite effect of HAMLET (human alpha-lactalbumin made lethal to tumor cells), a human milk protein-lipid complex and amoxicillin on microbial ecology using an ex vivo oral biofilm model with pooled saliva samples. HAMLET was chosen due to its multi-targeted antimicrobial mechanism, together with its synergistic effect with antibiotics on single species pathogens, and low risk of resistance development. The combination of HAMLET and low concentrations of amoxicillin significantly reduced biofilm viability, while each of them alone had little or no impact. Using a whole metagenomics approach, we found that the combination promoted a remarkable shift in overall microbial composition compared to the untreated samples. A large proportion of the bacterial species in the combined treatment were Lactobacillus crispatus, a species with probiotic effects, whereas it was only detected in a minor fraction in untreated samples. Although resistome analysis indicated no major shifts in alpha-diversity, the results showed the presence of TEM beta-lactamase genes in low proportions in all treated samples but absence in untreated samples. Our study illustrates HAMLET’s capability to alter the effects of amoxicillin on the oral microbiome and potentially favor the growth of selected probiotic bacteria when in combination. The findings extend previous knowledge on the combined effects of HAMLET and antibiotics against target pathogens to include potential modulatory effects on polymicrobial biofilms of human origin.
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Brar, Navdeep Kaur; Dhariwal, Achal; Åmdal, Heidi Aarø; Junges, Roger; Salvadori, Gabriela & Baker, J.L.
[Vis alle 8 forfattere av denne artikkelen]
(2024).
Exploring ex vivo biofilm dynamics: consequences of low ampicillin concentrations on the human oral microbiome.
npj Biofilms and Microbiomes.
10(1).
doi:
10.1038/s41522-024-00507-7.
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Prolonged exposure to antibiotics at low concentration can promote processes associated with bacterial biofilm formation, virulence and antibiotic resistance. This can be of high relevance in microbial communities like the oral microbiome, where commensals and pathogens share a common habitat and where the total abundance of antibiotic resistance genes surpasses the abundance in the gut. Here, we used an ex vivo model of human oral biofilms to investigate the impact of ampicillin on biofilm viability. The ecological impact on the microbiome and resistome was investigated using shotgun metagenomics. The results showed that low concentrations promoted significant shifts in microbial taxonomic profile and could enhance biofilm viability by up to 1 to 2-log. For the resistome, low concentrations had no significant impact on antibiotic resistance gene (ARG) diversity, while ARG abundance decreased by up to 84%. A positive correlation was observed between reduced microbial diversity and reduced ARG abundance. The WHO priority pathogens Streptococcus pneumoniae and Staphylococcus aureus were identified in some of the samples, but their abundance was not significantly altered by ampicillin. Most of the antibiotic resistance genes that increased in abundance in the ampicillin group were associated with streptococci, including Streptococcus mitis, a well-known potential donor of ARGs to S. pneumoniae. Overall, the results highlight the potential of using the model to further our understanding of ecological and evolutionary forces driving antimicrobial resistance in oral microbiomes.
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Dhariwal, Achal; Rajar, Polona; Silva, Gabriela Salvadori Da; Åmdal, Heidi Aarø; Berild, Dag & Saugstad, Ola Didrik
[Vis alle 11 forfattere av denne artikkelen]
(2024).
Prolonged hospitalization signature and early antibiotic effects on the nasopharyngeal resistome in preterm infants.
Nature Communications.
15(1).
doi:
10.1038/s41467-024-50433-7.
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Respiratory pathogens, commonly colonizing nasopharynx, are among the leading causes of death due to antimicrobial resistance. Yet, antibiotic resistance determinants within nasopharyngeal microbial communities remain poorly understood. In this prospective cohort study, we investigate the nasopharynx resistome development in preterm infants, assess early antibiotic impact on its trajectory, and explore its association with clinical covariates using shotgun metagenomics. Our findings reveal widespread nasopharyngeal carriage of antibiotic resistance genes (ARGs) with resistomes undergoing transient changes, including increased ARG diversity, abundance, and composition alterations due to early antibiotic exposure. ARGs associated with the critical nosocomial pathogen Serratia marcescens persist up to 8–10 months of age, representing a long-lasting hospitalization signature. The nasopharyngeal resistome strongly correlates with microbiome composition, with inter-individual differences and postnatal age explaining most of the variation. Our report on the collateral effects of antibiotics and prolonged hospitalization underscores the urgency of further studies focused on this relatively unexplored reservoir of pathogens and ARGs.
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Dhariwal, Achal; Bråten, Lars Christian Haugli; Sturød, Kjersti; Silva, Gabriela Salvadori Da; Bargheet, Ahmed & Åmdal, Heidi Aarø
[Vis alle 11 forfattere av denne artikkelen]
(2023).
Differential response to prolonged amoxicillin treatment: long-term resilience of the microbiome versus long-lasting perturbations in the gut resistome.
Gut microbes.
ISSN 1949-0976.
15(1).
doi:
10.1080/19490976.2022.2157200.
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The collateral impact of antibiotics on the microbiome has attained increasing attention. However, the ecological consequences of long-term antibiotic exposure on the gut microbiome, including anti- biotic resistance, are still limited. Here, we investigated long-term exposure effects to amoxicillin on the human gut microbiome and resistome. Fecal samples were collected from 20 patients receiving 3-months of amoxicillin or placebo treatment as part of a Norwegian multicenter clinical trial on chronic low back pain (AIM study). Samples were collected at baseline, last day of treatment, and 9 months after antibiotic cessation. The abundance and diversity of microbial and resistome composi- tion were characterized using whole shotgun and functional metagenomic sequencing data. While the microbiome profiles of placebo subjects were stable over time, discernible changes in diversity and overall microbiome composition were observed after amoxicillin treatment. In particular, health- associated short-chain fatty acid producing species significantly decreased in proportion. However, these changes were short-lived as the microbiome showed overall recovery 9 months post-treatment. On the other hand, exposure to long-term amoxicillin was associated with an increase in total antimicrobial resistance gene load and diversity of antimicrobial resistance genes, with persistent changes even at 9 months post-treatment. Additionally, beta-lactam resistance was the most affected antibiotic class, suggesting a targeted response to amoxicillin, although changes at the gene level varied across individuals. Overall, our results suggest that the impact of prolonged amoxicillin exposure was more explicit and long-lasting in the fecal resistome than in microbiome composition. Such information is relevant for designing rational administration guidelines for antibiotic therapies.
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Singh, Yogesh; Trautwein, Christoph; Romani, Joan; Salker, Madhuri S.; Neckel, Peter H. & Fraccaroli, Isabel
[Vis alle 17 forfattere av denne artikkelen]
(2023).
Overexpression of human alpha-Synuclein leads to dysregulated microbiome/metabolites with ageing in a rat model of Parkinson disease.
Molecular Neurodegeneration.
18(1).
doi:
10.1186/s13024-023-00628-1.
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Background Braak’s hypothesis states that sporadic Parkinson’s disease (PD) follows a specific progression of pathology from the peripheral to the central nervous system, and this progression can be monitored by detecting the accumulation of alpha-Synuclein (α-Syn) protein. Consequently, there is growing interest in understanding how the gut (commensal) microbiome can regulate α-Syn accumulation, as this could potentially lead to PD. Methods We used 16S rRNA and shotgun sequencing to characterise microbial diversity. 1H-NMR was employed to understand the metabolite production and intestinal inflammation estimated using ELISA and RNA-sequencing from feces and the intestinal epithelial layer respectively. The Na+ channel current and gut permeability were measured using an Ussing chamber. Immunohistochemistry and immunofluorescence imaging were applied to detect the α-Syn protein. LC-MS/MS was used for characterization of proteins from metabolite treated neuronal cells. Finally, Metascape and Ingenuity Pathway Analysis (IPA) bioinformatics tools were used for identification of dysregulated pathways. Results We studied a transgenic (TG) rat model overexpressing the human SNCA gene and found that a progressive gut microbial composition alteration characterized by the reduction of Firmicutes to Bacteroidetes ratio could be detected in the young TG rats. Interestingly, this ratio then increased with ageing. The dynamics of Lactobacillus and Alistipes were monitored and reduced Lactobacillus and increased Alistipes abundance was discerned in ageing TG rats. Additionally, the SNCA gene overexpression resulted in gut α-Syn protein expression and increased with advanced age. Further, older TG animals had increased intestinal inflammation, decreased Na+ current and a robust alteration in metabolite production characterized by the increase of succinate levels in feces and serum. Manipulation of the gut bacteria by short-term antibiotic cocktail treatment revealed a complete loss of short-chain fatty acids and a reduction in succinate levels. Although antibiotic cocktail treatment did not change α-Syn expression in the enteric nervous system of the colon, however, reduced α-Syn expression was detected in the olfactory bulbs (forebrain) of the TG rats. Conclusion Our data emphasize that the gut microbiome dysbiosis synchronous with ageing leads to a specific alteration of gut metabolites and can be modulated by antibiotics which may affect PD pathology.
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Rajar, Polona; Dhariwal, Achal; Silva, Gabriela Salvadori Da; Junges, Roger; Åmdal, Heidi Aarø & Berild, Dag
[Vis alle 12 forfattere av denne artikkelen]
(2022).
Microbial DNA extraction of high-host content and low biomass samples: Optimized protocol for nasopharynx metagenomic studies.
Frontiers in Microbiology.
13,
s. 1–15.
doi:
10.3389/fmicb.2022.1038120.
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Introduction Low microbial biomass and high human DNA content in nasopharyngeal aspirate samples hinder comprehensive characterization of microbiota and resistome. We obtained samples from premature infants, a group with increased risk of developing respiratory disorders and infections, and consequently frequent exposure to antibiotics. Our aim was to devise an optimal protocol for handling nasopharyngeal aspirate samples from premature infants, focusing on host DNA depletion and microbiome and resistome characterization. Methods Three depletion and three DNA extraction protocols were compared, using RT-PCR and whole metagenome sequencing to determine the efficiency of human DNA removal, taxonomic profiling and assignment of antibiotic resistance genes. Protocols were tested using mock communities, as well as pooled and individual patient samples. Results The only extraction protocol to retrieve the expected DNA yield from mock community samples was based on a lytic method to improve Gram positive recovery (MasterPure™). Host DNA content in non-depleted aliquots from pooled patient samples was 99%. Only samples depleted with MolYsis™ showed satisfactory, but varied reduction in host DNA content, in both pooled and individual patient samples, allowing for microbiome and resistome characterisation (host DNA content from 15% to 98%). Other depletion protocols either retrieved too low total DNA yields, preventing further analysis, or failed to reduce host DNA content. By using Mol_MasterPure protocol on aliquots from pooled patient samples, we increased the number of bacterial reads by 7.6 to 1,725.8-fold compared to non-depleted reference samples. PCR results were indicative of achieved microbial enrichment. Individual patient samples processed with Mol_MasterPure protocol varied greatly in total DNA yield, host DNA content (from 40% to 98%), species and antibiotic resistance gene richness. Discussion Despite high human DNA and low microbial biomass content in nasopharynx aspirates of preterm infants, we were able to reduce host DNA content to levels compatible with downstream shotgun metagenomic analysis, including bacterial species identification and coverage of antibiotic resistance genes. Whole metagenomic sequencing of microbes colonizing the nasopharynx may contribute to explaining the possible role of airway microbiota in respiratory conditions and reveal carriage of antibiotic resistance genes.
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Dhariwal, Achal; Junges, Roger; Chen, Tsute & Petersen, Fernanda Cristina
(2021).
ResistoXplorer: a web-based tool for visual, statistical and exploratory data analysis of resistome data.
NAR Genomics and Bioinformatics.
3.
doi:
10.1093/nargab/lqab018.
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The study of resistomes using whole metagenomic sequencing enables high-throughput identification of resistance genes in complex microbial communities, such as the human microbiome. Over recent years, sophisticated and diverse pipelines have been established to facilitate raw data processing and annotation. Despite the progress, there are no easy-to-use tools for comprehensive visual, statistical and functional analysis of resistome data. Thus, exploration of the resulting large complex datasets remains a key bottleneck requiring robust computational resources and technical expertise, which creates a significant hurdle for advancements in the field. Here, we introduce ResistoXplorer, a user-friendly tool that integrates recent advancements in statistics and visualization, coupled with extensive functional annotations and phenotype collection, to enable high-throughput analysis of common outputs generated from metagenomic resistome studies. ResistoXplorer contains three modules—the ‘Antimicrobial Resistance Gene Table’ module offers various options for composition profiling, functional profiling and comparative analysis of resistome data; the ‘Integration’ module supports integrative exploratory analysis of resistome and microbiome abundance profiles derived from metagenomic samples; finally, the ‘Antimicrobial Resistance Gene List’ module enables users to intuitively explore the associations between antimicrobial resistance genes and the microbial hosts using network visual analytics to gain biological insights. ResistoXplorer is publicly available at http://www.resistoxplorer.no.
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Bissinger, Rosi; Nemkov, Travis; D'Alessandro, Angelo; Grau, Marijke; Dietz, Thomas & Bohnert, Bernhard N.
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(2021).
Proteinuric chronic kidney disease is associated with altered red blood cell lifespan, deformability and metabolism.
Kidney International.
ISSN 0085-2538.
100(6),
s. 1227–1239.
doi:
10.1016/j.kint.2021.08.024.
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Anemia is a common complication of chronic kidney disease, affecting the quality of life of patients. Among various factors, such as iron and erythropoietin deficiency, reduced red blood cell (RBC) lifespan has been implicated in the pathogenesis of anemia. However, mechanistic data on in vivo RBC dysfunction in kidney disease are lacking. Herein, we describe the development of chronic kidney disease-associated anemia in mice with proteinuric kidney disease resulting from either administration of doxorubicin or an inducible podocin deficiency. In both experimental models, anemia manifested at day 10 and progressed at day 30 despite increased circulating erythropoietin levels and erythropoiesis in the bone marrow and spleen. Circulating RBCs in both mouse models displayed altered morphology and diminished osmotic-sensitive deformability together with increased phosphatidylserine externalization on the outer plasma membrane, a hallmark of RBC death. Fluorescence-labelling of RBCs at day 20 of mice with doxorubicin-induced kidney disease revealed premature clearance from the circulation. Metabolomic analyses of RBCs from both mouse models demonstrated temporal changes in redox recycling pathways and Lands’ cycle, a membrane lipid remodeling process. Anemic patients with proteinuric kidney disease had an increased proportion of circulating phosphatidylserine-positive RBCs. Thus, our observations suggest that reduced RBC lifespan, mediated by altered RBC metabolism, reduced RBC deformability, and enhanced cell death contribute to the development of anemia in proteinuric kidney disease.
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Dhariwal, Achal; Junges, Roger; Chen, Tsute & Petersen, Fernanda Cristina
(2020).
ResistoXplorer: a web-based tool for visual, statistical and exploratory data analysis of resistome data.
BioRxiv.
ISSN 0362-4331.
doi:
10.1101/2020.08.14.250837.
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Singh, Yogesh; Christoph, Trautwein; Dhariwal, Achal; Salkar, Madhuri S.; Alauddin, Md & Zizmare, Laimdota et al.
[Vis alle 19 forfattere av denne artikkelen]
(2020).
DJ-1 (Park7) affects the gut microbiome, metabolites and development of Innate Lymphoid cells (ILCs).
Scientific Reports.
doi:
10.1038/s41598-020-72903-w.
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Abstract The proper communication between gut and brain is pivotal for the maintenance of health and, dysregulation of the gut-brain axis can lead to several clinical disorders. In Parkinson’s disease (PD) 85% of all patients experienced constipation many years before showing any signs of motor phenotypes. For differential diagnosis and preventive treatment, there is an urgent need for the identification of biomarkers indicating early disease stages long before the disease phenotype manifests. DJ-1 is a chaperone protein involved in the protection against PD and genetic mutations in this protein have been shown to cause familial PD. However, how the deficiency of DJ-1 influences the risk of PD remains incompletely understood. In the present study, we provide evidence that DJ-1 is implicated in shaping the gut microbiome including; their metabolite production, inflammation and innate immune cells (ILCs) development. We revealed that deficiency of DJ-1 leads to a significant increase in two specific genera/species, namely Alistipes and Rikenella . In DJ-1 knock-out (DJ-1 -/- ) mice the production of fecal calprotectin and MCP-1 inflammatory proteins were elevated. Fecal and serum metabolic profile showed that malonate which influences the immune system was significantly more abundant in DJ-1 −/− mice. DJ-1 appeared also to be involved in ILCs development. Further, inflammatory genes related to PD were augmented in the midbrain of DJ-1 −/− mice. Our data suggest that metabolites and inflammation produced in the gut could be used as biomarkers for PD detection. Perhaps, these metabolites and inflammatory mediators could be involved in triggering inflammation resulting in PD pathology.
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Soni, Nancy; Hegde, Niranjan; Dhariwal, Achal & Kushalappa, Ajjamada C.
(2020).
Role of laccase gene in wheat NILs differing at QTL-Fhb1 for resistance against Fusarium head blight.
Plant Science.
ISSN 0168-9452.
298.
doi:
10.1016/j.plantsci.2020.110574.
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Khan, Nargis; Dhariwal, Achal; Mendonca, Laura; Fontes, Ghislaine; Dick, Menzies & Xia, Jianguo et al.
(2019).
Intestinal dysbiosis compromises alveolar macrophage immunity to Mycobacterium tuberculosis.
Mucosal Immunology.
ISSN 1933-0219.
doi:
10.1038/s41385-019-0147-3.
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Sturød, Kjersti; Dhariwal, Achal; Dahle, Ulf R; Vestrheim, Didrik Frimann & Petersen, Fernanda Cristina
(2019).
Impact of narrow-spectrum penicillin V on the oral and faecal resistome in a young child treated for otitis media.
Journal of Global Antimicrobial Resistance.
ISSN 2213-7165.
20,
s. 290–297.
doi:
10.1016/j.jgar.2019.08.004.
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Objectives Antibiotic overuse has led to the global emergence of antimicrobial-resistant bacteria, and children are among the most frequent users of antibiotics. Most studies with broad-spectrum antibiotics show a severe impact on resistome development in patients. Although narrow-spectrum antibiotics are believed to have fewer side effects, their impact on the microbiome and resistome is mostly unknown. The aim of this study was to investigate the impact of the narrow-spectrum antibiotic phenoxymethylpenicillin (penicillin V) on the microbiome and resistome of a child treated for acute otitis media. Methods Oral and faecal samples were collected from a 1-year-old child before (Day 0) and after (Days 5 and 30) receiving penicillin V for otitis media. Metagenomic sequencing data were analysed to determine taxonomic profiling using Kraken and Bracken software, and resistance profiling using KMA in combination with the ResFinder database. Results In the oral samples, antimicrobial resistance genes (ARGs) belonging to four classes were identified at baseline. At Day 5, the abundance of some ARGs was increased, whereas some remained unchanged and others could no longer be detected. At Day 30, most ARGs had returned to baseline levels or lower. In the faecal samples, seven ARGs were observed at baseline and five at Day 5. At Day 30, the number of ARGs had increased to 21. Conclusions Following penicillin V, we observed a remarkable enrichment of the aecal resistome, indicating that even narrow-spectrum antibiotics may have important consequences in selecting for a more resistant microbiome.
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Dhariwal, Achal; Chong, Jasmine; Habib, Salam; King, Irah L.; Agellon, Luis B. & Jianguo, Xia
(2017).
MicrobiomeAnalyst: a web-based tool for comprehensive statistical, visual and meta-analysis of microbiome data.
Nucleic Acids Research (NAR).
ISSN 0305-1048.
45,
s. W180–W188.
doi:
10.1093/nar/gkx295.
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Shawrob, Kazi Shefaul Mulk; Dhariwal, Achal; Salvadori, Gabriela; Gladstone, Rebecca Ashley & Junges, Roger
(2025).
Global Dynamics of Antibiotic Resistance in Streptococcus pneumoniae.
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Dhariwal, Achal & Petersen, Fernanda Cristina
(2025).
Early-life Antibiotics and Hospitalization Influence Nasopharyngeal Microbiome Dynamics in preterm infants.
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Shekhar, Sudhanshu; Šrůtková, Dagmar; Dhariwal, Achal; Petersen, Fernanda Cristina & Schwarzer, Martin
(2025).
Human Nasal Microbiota Transplantation in Germ-Free Mice: A Model for Therapeutic Exploration.
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Petersen, Fernanda Cristina & Dhariwal, Achal
(2024).
Antibiotic use: Microbial aftermath.
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Dhariwal, Achal; Dahle, Ulf R; Baker, Jonathon; Filho, Antonio Pedro Ricomini; Tabchoury, Cinthia & Petersen, Fernanda Cristina
(2024).
Collaborative Approaches to Antimicrobial Resistance Research in Dentistry.
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Shawrob, Kazi; Dhariwal, Achal; Silva, Gabriela Salvadori Da; Petersen, Fernanda Cristina & Junges, Roger
(2024).
Mapping antibiotic resistance patterns in Streptococcus pneumoniae.
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Shawrob, Kazi Shefaul Mulk; Dhariwal, Achal; Silva, Gabriela Salvadori Da; Petersen, Fernanda Cristina & Junges, Roger
(2024).
Mapping antibiotic resistance patterns in Streptococcus pneumoniae.
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Dhariwal, Achal & Petersen, Fernanda Cristina
(2024).
Impacts of Population-Level Antibiotic Consumption on Antimicrobial Resistance: A One-Health Approach.
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Dhariwal, Achal & Petersen, Fernanda Cristina
(2024).
Exploring the antibiotic resistance gene profiles in the nasopharynx of Preterm Infants: Longitudinal impact of hospitalization and antibiotic exposure.
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Introducing our research, we address the urgent need to understand antibiotic
resistance within respiratory microbial communities, which are significant contributors to
antimicrobial resistance-related mortality. Utilizing shotgun metagenomics, our study
investigates the nasopharynx resistome development in preterm infants, particularly focusing
on the impact of early antibiotic exposure and its association with clinical factors. Our
comprehensive analysis reveals widespread nasopharyngeal carriage of antibiotic resistance
genes (ARGs) and dynamic changes in resistome composition, diversity, and abundance
following antibiotic administration. Notably, persistent ARGs linked with Serratia marcescens
underscore the enduring impact of hospitalization. These findings emphasize the critical
importance of further exploring this reservoir of pathogens and ARGs, shedding light on the
collateral effects of antibiotics and prolonged hospital stays.
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Dhariwal, Achal & Petersen, Fernanda Cristina
(2024).
ResistoXplorer 2.0: an improved bioinformatics tool for comprehensive statistical, visual and integrative analysis of AMR metagenomic sequencing data.
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Background and Aim: Antimicrobial resistance (AMR) is considered as one of the most urgent threats to global public health, and metagenomic-based investigations featuring high-throughput analysis of sequence data are increasingly common and important across human, animal, agricultural and environmental sectors. The resulting large and complex datasets often require powerful, yet user-friendly bioinformatics tools to unveil key patterns, identify significant biomarkers, and explore potential activities.
Method: We previously introduced ResistoXplorer, a user-friendly web-based tool for bench researchers and clinicians to perform comprehensive downstream analysis on AMR genes (resistome) abundance profiles. ResistoXplorer is developed using three open-source programming languages: Java, R, and JavaScript.
Results: Compared to the previous version, ResistoXplorer 2.0 features three new modules: (i) a raw data processing module for metagenomic sequencing data processing and ARGs annotation that connects directly with the ARG Table module for comprehensive visual, statistical and exploratory analysis; (ii) a time series analysis module that incorporates robust, powerful as well as more advanced statistical and visualization approaches tailored for longitudinal studies; and (iii) an interactive 2D/3D network-based visual analytics system providing the topological view of public ARG databases to discover and gain novel biological insights. Other significant improvements include interactive visualizations for common graphical outputs, updated statistical methods to perform integrative analysis of paired microbiome and resistome datasets. The underlying ResistoXplorerR package will also be released to enable transparent and reproducible analysis.
Applications: ResistoXplorer will be a one stop shop that allows AMR researchers to thoroughly explore their metagenomic data via intuitive web interfaces. Development of such bioinformatics tool suite promotes the application of metagenomics-based investigations for surveillance, enhance our understanding of AMR and its dynamics in humans, animals, and environmental microbial communities. ResistoXplorer 2.0 will be publicly available at resistoxplorer.no.
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Dhariwal, Achal; Petersen, Fernanda Cristina & Salvadori, Gabriela
(2024).
Prolonged hospitalization signature and early
antibiotic effects on the nasopharyngeal resistome in
preterm infants.
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Shawrob, Kazi Shefaul Mulk; Dhariwal, Achal; Silva, Gabriela Salvadori Da; Petersen, Fernanda Cristina & Junges, Roger
(2024).
Insights into multidrug resistance in Streptococcus pneumoniae.
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Dhariwal, Achal; Petersen, Fernanda Cristina & Salvadori, Gabriela
(2024).
Prolonged hospitalization signature and early antibiotic effects on the nasopharyngeal resistome in preterm infants.
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Dhariwal, Achal & Petersen, Fernanda Cristina
(2024).
Hands-on Bioinformatics on AMR data.
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Dhariwal, Achal & Petersen, Fernanda Cristina
(2024).
Bioinformatics (Upstream) analysis of metagenomic resistome data.
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Dhariwal, Achal; Petersen, Fernanda Cristina; Chen, Tsute & Baker, Jonathon
(2023).
Introduction to Resistome: key concepts and hands-on analysis.
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Dhariwal, Achal & Petersen, Fernanda Cristina
(2022).
Using ResistoXplorer for comprehensive visual, statistical, and exploratory analysis of AMR metagenomic data.
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Dhariwal, Achal
(2022).
Impact of Long-Term Amoxicillin Treatment on the Gut Microbiome and Resistome.
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Brar, Navdeep Kaur; Dhariwal, Achal; Junges, Roger; Håkansson, Anders & Petersen, Fernanda Cristina
(2022).
Potential of HAMLET, a human milk protein-lipid complex, to modulate ecological changes in the oral microbiome induced by amoxicillin.
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Dhariwal, Achal & Petersen, Fernanda Cristina
(2022).
Impact of Long-Term Amoxicillin Treatment on the Gut Microbiome and Resistome.
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Dhariwal, Achal & Petersen, Fernanda Cristina
(2022).
ResistoXplorer: a web-based tool for visual, statistical and exploratory data analysis of resistome data.
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Brar, Navdeep Kaur; Dhariwal, Achal; Åmdal, Heidi Aarø; Junges, Roger; Salvadori, Gabriela & Petersen, Fernanda Cristina
(2022).
The Impact of Ampicillin on the Oral Microbiome and Resistome.
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Rajar, Polona; Dhariwal, Achal; Salvadori, Gabriela; Junges, Roger; Åmdal, Heidi Aarø & Berild, Dag
[Vis alle 12 forfattere av denne artikkelen]
(2022).
Microbial DNA extraction of high-host content and low biomass samples: optimized protocol for nasopharynx metagenomic studies.
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Low microbial biomass and high human DNA content in nasopharyngeal aspirate samples hinder comprehensive characterization of microbiota and resistome. We obtained samples from premature infants, a group with increased risk of developing respiratory disorders and infections, and consequently frequent exposure to antibiotics. Our aim was to devise an optimal protocol for handling nasopharyngeal aspirates from premature infants, focusing on host DNA depletion and microbiome and resistome characterization. Three depletion and three DNA extraction protocols were compared, using RT-PCR and whole metagenome sequencing to determine the efficiency of human DNA removal, taxonomic profiling and assignment of antibiotic resistance genes. Protocols were tested using mock communities, as well as pooled and individual patient samples. The only extraction protocol to retrieve the expected DNA yield from mock community samples was based on a lytic method to improve Gram positive recovery (MasterPure™). Only samples depleted with MolYsis™ showed satisfactory, but varied reduction in host DNA content, in both pooled and individual patient samples, allowing for microbiome and resistome characterisation (host DNA content from 15% to 98%). PCR results were indicative of achieved microbial enrichment. Despite high human DNA and low microbial biomass content in nasopharynx aspirates of preterm infants, we were able to reduce host DNA content to levels compatible with downstream shotgun metagenomic analysis, including bacterial species identification and coverage of antibiotic resistance genes. Whole metagenomic sequencing of microbes colonizing the nasopharynx may contribute to explaining the possible role of airway microbiota in respiratory conditions and reveal carriage of antibiotic resistance genes.
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Dhariwal, Achal & Petersen, Fernanda Cristina
(2021).
Resistoxplorer: A web-based tool for visual, statistical and exploratory analysis of resistome data.
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Petersen, Fernanda Cristina; Dhariwal, Achal; Sturød, Kjersti & Nickelsen, Trine
(2020).
Babyer får penicillin ? og uheldige bakterier blusser opp.
[Internet].
Apollon.
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Dhariwal, Achal; Petersen, Fernanda Cristina; Junges, Roger & Chen, Tsute
(2020).
ResistoXplorer: a web-based tool for visual, statistical and
exploratory data analysis of resistome data.
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Dhariwal, Achal & Petersen, Fernanda Cristina
(2019).
Visual exploration and network-based analysis of resistome data.
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Dhariwal, Achal; Junges, Roger & Petersen, Fernanda Cristina
(2019).
Exploratory analysis and Visualization of resistome data.
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Abstract: Recently, antimicrobial resistance (AMR) has gained everybody’s attention at a global level due to its impact on public health. Nation-wide surveillance efforts have been going on for characterization of these resistance determinants responsible for AMR. Due to advancements in metagenomics, comprehensive databases have been already established providing hierarchical information such as class, group and mechanism of these antibiotic resistance genes (ARGs). Additionally, some recently developed tools are also able to quantify the abundance of these ARGs present in any metagenomic sample. However, it is still challenging to perform bioinformatics analysis and interpretation of such data. Further, there is no such specific tool developed to support comprehensive downstream analysis and visualization from resistome data. As a result, we are aiming to develop ResistoAnalyst, a user-friendly web-based tool that integrates recent advancements in visualization and statistics techniques, integrated with several comprehensive databases, to enable comprehensive analysis of resistome data generated from metagenomics studies. Development of such tool will enable most clinicians, bench researchers to better understand, and generate hypothesis from their own data in real time. Additionally, ResistoAnalyst will be a valuable resource for sequence-based surveillance and monitoring of antibiotic usage and resistome development.
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Dhariwal, Achal & Petersen, Fernanda Cristina
(2018).
Network-based analysis of Resistome data.
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Dutta, Anirban; Dhariwal, Achal; Nangia, Sushma & Mande, Sharmila
(2018).
Development and validation of comprehensive ‘perinatal risk factors based clinical score' for management of early onset neonatal sepsis in preterm neonates less than 35 weeks gestation -a prospective observational study.
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Participants from the "Born in the Twilight" team
Dr. Sushma Nangia, LHMC
Mr. Achal Dhariwal, Univ. of Oslo
Dr. Sharmila Mande, TCS
Dr. Anirban Dutta, TCS
Growing resistance to antimicrobial drugs in pathogenic microorganisms has become the most important problems of 21st century. In a recent report it is estimated that approximately 0.7 million people die every year from drug resistant strains of microbes. The number will increase to 10 million by 2050, surpassing cancer (8.2 million deaths per year). Strengthening surveillance systems for combatting Antimicrobial Resistance (AMR) is an urgent and contemporary challenge.
The Indian Council for Medical Research, Delhi, India in collaboration with the Department of Informatics, University of Oslo, Norway and their partner HISP India is organizing a workshop for designing the Framework for development of an integrated surveillance system for AMR.
WORKSHOP DATES and Venue - November 12th and 13th, 2018, ICMR, New Delhi.
This 2-day workshop is an Indo-Norwegian initiative to brainstorm and conceptualize the way forward to design and develop a framework for an integrated AMR surveillance system, bringing together data from sources related to humans, climate and animal sources. The workshop will bring in experts from various domains of AMR (Humans, Animals and Climate), along with those in digital health technologies. Together, we will brainstorm to help develop an initial roadmap for the development of a One health network for the AMR surveillance.
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Dhariwal, Achal
(2018).
Statistical, Visual and Functional Analysis of Microbiome Data.
McGill University.
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Publisert
4. sep. 2018 12:42
- Sist endret
15. des. 2022 10:02