| 1. |
- 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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| 2. |
- Jacobson, Magdalena
(författare)
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Metagenomic sequencing of clinical samples reveals a single widespread clone of Lawsonia intracellularis responsible for porcine proliferative enteropathy
- 2020
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Ingår i: Microbial genomics. - : Microbiology Society. - 2057-5858. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Lawsonia intracellularis is a Gram-negative obligate intracellular bacterium that is the aetiological agent of proliferative enteropathy (PE), a common intestinal disease of major economic importance in pigs and other animal species. To date, progress in understanding the biology of L. intracellularis for improved disease control has been hampered by the inability to culture the organism in vitro. In particular, our understanding of the genomic diversity and population structure of clinical L. intercellularis is very limited. Here, we utilized a metagenomic shotgun approach to directly sequence and assemble 21 L. intracellularis genomes from faecal and ileum samples of infected pigs and horses across three continents. Phylogenetic analysis revealed a genetically monomorphic clonal lineage responsible for infections in pigs, with distinct subtypes associated with infections in horses. The genome was highly conserved, with 94% of genes shared by all isolates and a very small accessory genome made up of only 84 genes across all sequenced strains. In part, the accessory genome was represented by regions with a high density of SNPs, indicative of recombination events importing novel gene alleles. In summary, our analysis provides the first view of the population structure for L. intracellularis, revealing a single major lineage associated with disease of pigs. The limited diversity and broad geographical distribution suggest the recent emergence and clonal expansion of an important livestock pathogen.
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| 3. |
- Owen, Sian, V, et al.
(författare)
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A window into lysogeny : revealing temperate phage biology with transcriptomics
- 2020
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Ingår i: Microbial Genomics. - : Microbiology Society. - 2057-5858. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Prophages are integrated phage elements that are a pervasive feature of bacterial genomes. The fitness of bacteria is enhanced by prophages that confer beneficial functions such as virulence, stress tolerance or phage resistance, and these functions are encoded by 'accessory' or 'moron' loci. Whilst the majority of phage-encoded genes are repressed during lysogeny, accessory loci are often highly expressed. However, it is challenging to identify novel prophage accessory loci from DNA sequence data alone. Here, we use bacterial RNA-seq data to examine the transcriptional landscapes of five Salmonella prophages. We show that transcriptomic data can be used to heuristically enrich for prophage features that are highly expressed within bacterial cells and represent functionally important accessory loci. Using this approach, we identify a novel antisense RNA species in prophage BTP1, STnc6030, which mediates superinfection exclusion of phage BTP1. Bacterial transcriptomic datasets are a powerful tool to explore the molecular biology of temperate phages.
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| 4. |
- Xu, Feifei, et al.
(författare)
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The compact genome of Giardia muris reveals important steps in the evolution of intestinal protozoan parasites
- 2020
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Ingår i: Microbial Genomics. - : Microbiology Society. - 2057-5858. ; 6:8
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Diplomonad parasites of the genus Giardia have adapted to colonizing different hosts, most notably the intestinal tract of mammals. The human-pathogenic Giardia species, Giardia intestinalis, has been extensively studied at the genome and gene expression level, but no such information is available for other Giardia species. Comparative data would be particularly valuable for Giardia muris, which colonizes mice and is commonly used as a prototypic in vivo model for investigating host responses to intestinal parasitic infection. Here we report the draft-genome of G. muris. We discovered a highly streamlined genome, amongst the most densely encoded ever described for a nuclear eukaryotic genome. G. muris and G. intestinalis share many known or predicted virulence factors, including cysteine proteases and a large repertoire of cysteine-rich surface proteins involved in antigenic variation. Different to G. intestinalis, G. muris maintains tandem arrays of pseudogenized surface antigens at the telomeres, whereas intact surface antigens are present centrally in the chromosomes. The two classes of surface antigens engage in genetic exchange. Reconstruction of metabolic pathways from the G. muris genome suggest significant metabolic differences to G. intestinalis. Additionally, G. muris encodes proteins that might be used to modulate the prokaryotic microbiota. The responsible genes have been introduced in the Giardia genus via lateral gene transfer from prokaryotic sources. Our findings point to important evolutionary steps in the Giardia genus as it adapted to different hosts and it provides a powerful foundation for mechanistic exploration of host-pathogen interaction in the G. muris – mouse pathosystem.Importance The Giardia genus comprises eukaryotic single-celled parasites that infect many animals. The Giardia intestinalis species complex, which can colonize and cause diarrheal disease in humans and different animal hosts has been extensively explored at the genomic and cell biologic levels. Other Giardia species, such as the mouse parasite Giardia muris, have remained uncharacterized at the genomic level, hampering our understanding of in vivo host-pathogen interactions and the impact of host dependence on the evolution of the Giardia genus. We discovered that the G. muris genome encodes many of the same virulence factors as G. intestinalis. The G. muris genome has undergone genome contraction, potentially in response to a more defined infective niche in the murine host. We describe differences in metabolic and microbiome modulatory gene repertoire, mediated mainly by lateral gene transfer, that could be important for understanding infective success across the Giardia genus. Our findings provide new insights for the use of G. muris as a powerful model for exploring host-pathogen interactions in giardiasis.
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