One Small Step for a Yeast - Microevolution within Macrophages Renders Candida glabrata Hypervirulent Due to a Single Point Mutation
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{"title"=>"One Small Step for a Yeast - Microevolution within Macrophages Renders Candida glabrata Hypervirulent Due to a Single Point Mutation", "type"=>"journal", "authors"=>[{"first_name"=>"Sascha", "last_name"=>"Brunke", "scopus_author_id"=>"12240425000"}, {"first_name"=>"Katja", "last_name"=>"Seider", "scopus_author_id"=>"34873480700"}, {"first_name"=>"Daniel", "last_name"=>"Fischer", "scopus_author_id"=>"56060896300"}, {"first_name"=>"Ilse D.", "last_name"=>"Jacobsen", "scopus_author_id"=>"8676553500"}, {"first_name"=>"Lydia", "last_name"=>"Kasper", "scopus_author_id"=>"55565663100"}, {"first_name"=>"Nadja", "last_name"=>"Jablonowski", "scopus_author_id"=>"54401201500"}, {"first_name"=>"Anja", "last_name"=>"Wartenberg", "scopus_author_id"=>"56398256800"}, {"first_name"=>"Oliver", "last_name"=>"Bader", "scopus_author_id"=>"8092151300"}, {"first_name"=>"Adela", "last_name"=>"Enache-Angoulvant", "scopus_author_id"=>"14824949700"}, {"first_name"=>"Martin", "last_name"=>"Schaller", "scopus_author_id"=>"7103218210"}, {"first_name"=>"Christophe", "last_name"=>"d'Enfert", "scopus_author_id"=>"57150749600"}, {"first_name"=>"Bernhard", "last_name"=>"Hube", "scopus_author_id"=>"7003738705"}], "year"=>2014, "source"=>"PLoS Pathogens", "identifiers"=>{"issn"=>"15537374", "scopus"=>"2-s2.0-84908346385", "sgr"=>"84908346385", "pui"=>"600311023", "pmid"=>"25356907", "doi"=>"10.1371/journal.ppat.1004478"}, "id"=>"cb3eaa03-3ec1-3000-a1be-f25162de5a6f", "abstract"=>"Candida glabrata is one of the most common causes of candidemia, a life-threatening, systemic fungal infection, and is surpassed in frequency only by Candida albicans. Major factors contributing to the success of this opportunistic pathogen include its ability to readily acquire resistance to antifungals and to colonize and adapt to many different niches in the human body. Here we addressed the flexibility and adaptability of C. glabrata during interaction with macrophages with a serial passage approach. Continuous co-incubation of C. glabrata with a murine macrophage cell line for over six months resulted in a striking alteration in fungal morphology: The growth form changed from typical spherical yeasts to pseudohyphae-like structures - a phenotype which was stable over several generations without any selective pressure. Transmission electron microscopy and FACS analyses showed that the filamentous-like morphology was accompanied by changes in cell wall architecture. This altered growth form permitted faster escape from macrophages and increased damage of macrophages. In addition, the evolved strain (Evo) showed transiently increased virulence in a systemic mouse infection model, which correlated with increased organ-specific fungal burden and inflammatory response (TNFα and IL-6) in the brain. Similarly, the Evo mutant significantly increased TNFα production in the brain on day 2, which is mirrored in macrophages confronted with the Evo mutant, but not with the parental wild type. Whole genome sequencing of the Evo strain, genetic analyses, targeted gene disruption and a reverse microevolution experiment revealed a single nucleotide exchange in the chitin synthase-encoding CHS2 gene as the sole basis for this phenotypic alteration. A targeted CHS2 mutant with the same SNP showed similar phenotypes as the Evo strain under all experimental conditions tested. These results indicate that microevolutionary processes in host-simulative conditions can elicit adaptations of C. glabrata to distinct host niches and even lead to hypervirulent strains.", "link"=>"http://www.mendeley.com/research/one-small-step-yeast-microevolution-within-macrophages-renders-candida-glabrata-hypervirulent-due-si", "reader_count"=>21, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Student > Doctoral Student"=>2, "Researcher"=>5, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Student > Master"=>3, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Student > Doctoral Student"=>2, "Researcher"=>5, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Student > Master"=>3, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>11, "Medicine and Dentistry"=>3, "Veterinary Science and Veterinary Medicine"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>11}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Belgium"=>1, "Poland"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1772468"], "description"=>"<p>A. Mice were intravenously infected with 5×10<sup>7</sup><i>C. glabrata</i> cells on day 0. Body weight of animals was monitored daily. During the first four days, infection with the evolved strain (Evo) led to severe loss in body weight, in contrast to mice infected with the parental strain (WT). B. Fungal burden was determined by culture from tissue homogenates of five animals per treatment group and time point. The distribution of fungal burden differed significantly between the wild type (WT) and the evolved strain (Evo) at the early time point. In the brain, the burden on day 2 p.i. was more than 100× higher for the evolved strain than for the wild type (median 1.1×10<sup>7</sup> cfu/ml vs. 4.9×10<sup>4</sup> cfu/ml). This difference was not present at later time points (days 7 and 21 p.i.), and both strains persisted at comparable levels in the organ. C. Representative histological images of brain tissue of infected mice. Brains infected with the evolved strain (Evo) showed large and numerous microcolonies (upper right picture, microcolonies are indicated by black arrows). Evo cells formed larger clumps of cells; the wild type (WT) formed only few small microcolonies in the brain (upper and lower left picture, a microcolony is indicated by a black arrow). Please note that the PAS stain used does not allow reliable differentiation between neuronal and endothelial cells.</p>", "links"=>[], "tags"=>["morphology", "chs", "Whole Genome Sequencing", "snp", "alteration", "TNF α production", "niche", "analyses", "gene", "murine macrophage cell line", "transmission electron microscopy", "Evo strain", "Single Point Mutation Candida glabrata", "growth form", "phenotype", "cell wall architecture", "Macrophages Renders Candida glabrata Hypervirulent", "mouse infection model", "il", "facs"], "article_id"=>1223424, "categories"=>["Biological Sciences"], "users"=>["Sascha Brunke", "Katja Seider", "Daniel Fischer", "Ilse D. Jacobsen", "Lydia Kasper", "Nadja Jablonowski", "Anja Wartenberg", "Oliver Bader", "Adela Enache-Angoulvant", "Martin Schaller", "Christophe d'Enfert", "Bernhard Hube"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004478.g004", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Enhanced_virulence_and_altered_organ_tropism_of_the_evolved_strain_/1223424", "title"=>"Enhanced virulence and altered organ tropism of the evolved strain.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-30 03:19:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1772453"], "description"=>"<p>Macrophages were infected with WT and Evo cells at a ratio of 100∶1 at day 0 and the relative proportion between the two strains monitored daily. The ratio reversed after a few days of coincubation, demonstrating an advantage for the Evo strain during interaction with macrophages. Mean values and standard deviations of three independent experiments are shown.</p>", "links"=>[], "tags"=>["morphology", "chs", "Whole Genome Sequencing", "snp", "alteration", "TNF α production", "niche", "analyses", "gene", "murine macrophage cell line", "transmission electron microscopy", "Evo strain", "Single Point Mutation Candida glabrata", "growth form", "phenotype", "cell wall architecture", "Macrophages Renders Candida glabrata Hypervirulent", "mouse infection model", "il", "facs"], "article_id"=>1223418, "categories"=>["Biological Sciences"], "users"=>["Sascha Brunke", "Katja Seider", "Daniel Fischer", "Ilse D. Jacobsen", "Lydia Kasper", "Nadja Jablonowski", "Anja Wartenberg", "Oliver Bader", "Adela Enache-Angoulvant", "Martin Schaller", "Christophe d'Enfert", "Bernhard Hube"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004478.g002", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Increased_fitness_of_the_evolved_strain_in_macrophages_in_direct_competition_/1223418", "title"=>"Increased fitness of the evolved strain in macrophages in direct competition.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-30 03:19:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1772475"], "description"=>"<p>Single Nucleotide Polymorphisms distinguishing the wild type (WT) and the evolved strain (Evo).</p>", "links"=>[], "tags"=>["morphology", "chs", "Whole Genome Sequencing", "snp", "alteration", "TNF α production", "niche", "analyses", "gene", "murine macrophage cell line", "transmission electron microscopy", "Evo strain", "Single Point Mutation Candida glabrata", "growth form", "phenotype", "cell wall architecture", "Macrophages Renders Candida glabrata Hypervirulent", "mouse infection model", "il", "facs"], "article_id"=>1223431, "categories"=>["Biological Sciences"], "users"=>["Sascha Brunke", "Katja Seider", "Daniel Fischer", "Ilse D. Jacobsen", "Lydia Kasper", "Nadja Jablonowski", "Anja Wartenberg", "Oliver Bader", "Adela Enache-Angoulvant", "Martin Schaller", "Christophe d'Enfert", "Bernhard Hube"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004478.t001", "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Single_Nucleotide_Polymorphisms_distinguishing_the_wild_type_WT_and_the_evolved_strain_Evo_/1223431", "title"=>"Single Nucleotide Polymorphisms distinguishing the wild type (WT) and the evolved strain (Evo).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-10-30 03:19:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1772474"], "description"=>"<p>Following 24 h co-incubation with macrophages, the CHS2<sup>Evo</sup> strain, containing the Evo allele of the <i>CHS2</i> gene, elicited the same increased LDH release from macrophages as the Evo strain. Reintroduction of the wild type <i>CHS2</i> gene (CHS<sup>WT</sup>) into the WT strain did not lead to a significant change in its damage potential. (n≥3).</p>", "links"=>[], "tags"=>["morphology", "chs", "Whole Genome Sequencing", "snp", "alteration", "TNF α production", "niche", "analyses", "gene", "murine macrophage cell line", "transmission electron microscopy", "Evo strain", "Single Point Mutation Candida glabrata", "growth form", "phenotype", "cell wall architecture", "Macrophages Renders Candida glabrata Hypervirulent", "mouse infection model", "il", "facs"], "article_id"=>1223430, "categories"=>["Biological Sciences"], "users"=>["Sascha Brunke", "Katja Seider", "Daniel Fischer", "Ilse D. Jacobsen", "Lydia Kasper", "Nadja Jablonowski", "Anja Wartenberg", "Oliver Bader", "Adela Enache-Angoulvant", "Martin Schaller", "Christophe d'Enfert", "Bernhard Hube"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004478.g008", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Introduction_of_a_single_nucleotide_exchange_into_CHS2_results_in_increased_macrophage_damage_/1223430", "title"=>"Introduction of a single nucleotide exchange into <i>CHS2</i> results in increased macrophage damage.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-30 03:19:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1772470"], "description"=>"<p>Following alignment of Solexa/Illumina reads for the genomes of strains ATCC2001 and Evo on the <i>C. glabrata</i> reference genome, an average coverage score was calculated for each 1 kb region and normalized to the coverage obtained across the whole genome. These coverage ratio are shown in log2 scale. <i>C. glabrata</i> chromosomes A to M are shown in alternating black and grey colors. The location of SNPs identified in both strains relative to the reference genome is shown with green diamonds. The location of SNPs that distinguish the two strains is shown with red diamonds, the SNP on chromosome I responsible for the phenotype of strain Evo being shown in larger size. Note that several 1 kb regions harbored more than one SNP and are nevertheless represented using a single diamond.</p>", "links"=>[], "tags"=>["morphology", "chs", "Whole Genome Sequencing", "snp", "alteration", "TNF α production", "niche", "analyses", "gene", "murine macrophage cell line", "transmission electron microscopy", "Evo strain", "Single Point Mutation Candida glabrata", "growth form", "phenotype", "cell wall architecture", "Macrophages Renders Candida glabrata Hypervirulent", "mouse infection model", "il", "facs"], "article_id"=>1223426, "categories"=>["Biological Sciences"], "users"=>["Sascha Brunke", "Katja Seider", "Daniel Fischer", "Ilse D. Jacobsen", "Lydia Kasper", "Nadja Jablonowski", "Anja Wartenberg", "Oliver Bader", "Adela Enache-Angoulvant", "Martin Schaller", "Christophe d'Enfert", "Bernhard Hube"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004478.g006", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_No_large_scale_genomic_changes_but_single_SNP_differences_can_be_detected_between_WT_and_Evo_strains_/1223426", "title"=>"No large-scale genomic changes, but single SNP differences can be detected between WT and Evo strains.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-30 03:19:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1772456"], "description"=>"<p>A. The uptake by RAW 246.7 macrophages after 15 min to 6 hours of co-incubation was analyzed by differential staining (see <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004478#s4\" target=\"_blank\">Material and Methods</a>). Both strains were internalized to a similar extent a all time points. (n≥3). B. Following 24 h co-incubation, the evolved strain (Evo) damaged RAW 246.7 macrophages, but not epithelial TR 146 cells, to a higher extent than the parental strain (WT) as measured by lactate dehydrogenase (LDH) release. (n≥3).</p>", "links"=>[], "tags"=>["morphology", "chs", "Whole Genome Sequencing", "snp", "alteration", "TNF α production", "niche", "analyses", "gene", "murine macrophage cell line", "transmission electron microscopy", "Evo strain", "Single Point Mutation Candida glabrata", "growth form", "phenotype", "cell wall architecture", "Macrophages Renders Candida glabrata Hypervirulent", "mouse infection model", "il", "facs"], "article_id"=>1223421, "categories"=>["Biological Sciences"], "users"=>["Sascha Brunke", "Katja Seider", "Daniel Fischer", "Ilse D. Jacobsen", "Lydia Kasper", "Nadja Jablonowski", "Anja Wartenberg", "Oliver Bader", "Adela Enache-Angoulvant", "Martin Schaller", "Christophe d'Enfert", "Bernhard Hube"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004478.g003", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Microevolutionary_adaptation_results_in_altered_host_pathogen_interactions_/1223421", "title"=>"Microevolutionary adaptation results in altered host-pathogen interactions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-30 03:19:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1772479", "https://ndownloader.figshare.com/files/1772480", "https://ndownloader.figshare.com/files/1772481", "https://ndownloader.figshare.com/files/1772482", "https://ndownloader.figshare.com/files/1772483", "https://ndownloader.figshare.com/files/1772484", "https://ndownloader.figshare.com/files/1772485", "https://ndownloader.figshare.com/files/1772486", "https://ndownloader.figshare.com/files/1772487", "https://ndownloader.figshare.com/files/1772488", "https://ndownloader.figshare.com/files/1772489", "https://ndownloader.figshare.com/files/1772490", "https://ndownloader.figshare.com/files/1772491", "https://ndownloader.figshare.com/files/1772492"], "description"=>"<div><p><i>Candida glabrata</i> is one of the most common causes of candidemia, a life-threatening, systemic fungal infection, and is surpassed in frequency only by <i>Candida albicans</i>. Major factors contributing to the success of this opportunistic pathogen include its ability to readily acquire resistance to antifungals and to colonize and adapt to many different niches in the human body. Here we addressed the flexibility and adaptability of <i>C. glabrata</i> during interaction with macrophages with a serial passage approach. Continuous co-incubation of <i>C. glabrata</i> with a murine macrophage cell line for over six months resulted in a striking alteration in fungal morphology: The growth form changed from typical spherical yeasts to pseudohyphae-like structures – a phenotype which was stable over several generations without any selective pressure. Transmission electron microscopy and FACS analyses showed that the filamentous-like morphology was accompanied by changes in cell wall architecture. This altered growth form permitted faster escape from macrophages and increased damage of macrophages. In addition, the evolved strain (Evo) showed transiently increased virulence in a systemic mouse infection model, which correlated with increased organ-specific fungal burden and inflammatory response (TNFα and IL-6) in the brain. Similarly, the Evo mutant significantly increased TNFα production in the brain on day 2, which is mirrored in macrophages confronted with the Evo mutant, but not with the parental wild type. Whole genome sequencing of the Evo strain, genetic analyses, targeted gene disruption and a reverse microevolution experiment revealed a single nucleotide exchange in the chitin synthase-encoding <i>CHS2</i> gene as the sole basis for this phenotypic alteration. A targeted <i>CHS2</i> mutant with the same SNP showed similar phenotypes as the Evo strain under all experimental conditions tested. These results indicate that microevolutionary processes in host-simulative conditions can elicit adaptations of <i>C. glabrata</i> to distinct host niches and even lead to hypervirulent strains.</p></div>", "links"=>[], "tags"=>["morphology", "chs", "Whole Genome Sequencing", "snp", "alteration", "TNF α production", "niche", "analyses", "gene", "murine macrophage cell line", "transmission electron microscopy", "Evo strain", "Single Point Mutation Candida glabrata", "growth form", "phenotype", "cell wall architecture", "Macrophages Renders Candida glabrata Hypervirulent", "mouse infection model", "il", "facs"], "article_id"=>1223435, "categories"=>["Biological Sciences"], "users"=>["Sascha Brunke", "Katja Seider", "Daniel Fischer", "Ilse D. Jacobsen", "Lydia Kasper", "Nadja Jablonowski", "Anja Wartenberg", "Oliver Bader", "Adela Enache-Angoulvant", "Martin Schaller", "Christophe d'Enfert", "Bernhard Hube"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1004478.s001", "https://dx.doi.org/10.1371/journal.ppat.1004478.s002", "https://dx.doi.org/10.1371/journal.ppat.1004478.s003", "https://dx.doi.org/10.1371/journal.ppat.1004478.s004", "https://dx.doi.org/10.1371/journal.ppat.1004478.s005", "https://dx.doi.org/10.1371/journal.ppat.1004478.s006", "https://dx.doi.org/10.1371/journal.ppat.1004478.s007", "https://dx.doi.org/10.1371/journal.ppat.1004478.s008", "https://dx.doi.org/10.1371/journal.ppat.1004478.s009", "https://dx.doi.org/10.1371/journal.ppat.1004478.s010", "https://dx.doi.org/10.1371/journal.ppat.1004478.s011", "https://dx.doi.org/10.1371/journal.ppat.1004478.s012", "https://dx.doi.org/10.1371/journal.ppat.1004478.s013", "https://dx.doi.org/10.1371/journal.ppat.1004478.s014"], "stats"=>{"downloads"=>5, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/One_Small_Step_for_a_Yeast_Microevolution_within_Macrophages_Renders_Candida_glabrata_Hypervirulent_Due_to_a_Single_Point_Mutation/1223435", "title"=>"One Small Step for a Yeast - Microevolution within Macrophages Renders <i>Candida glabrata</i> Hypervirulent Due to a Single Point Mutation", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-10-30 03:19:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1772449"], "description"=>"<p>A. Daily passage of <i>C. glabrata</i> with RAW 264.7 macrophages led to the formation of a pseudohyphae-like growth phenotype. The left panel shows the <i>C. glabrata</i> Evo strain interacting with RAW 264.7 cells. In contrast to the parental strain (WT; middle picture) the evolved strain (Evo) formed clumps (right picture) in liquid media. B. The parental wild type (WT) formed smooth colonies on YPD agar; colonies of the evolved strain (Evo) grew with a strongly wrinkled morphology. Both strains appeared purple colored on CHROMagar plates (right picture), characteristic for <i>C. glabrata</i>. C. Transmission electron micrographs indicate a cell separation defect of the evolved (Evo) strain in comparison to the WT, and show enlarged septa between mother and daughter cells, as well as an increased thickness of the outer cell wall layer.</p>", "links"=>[], "tags"=>["morphology", "chs", "Whole Genome Sequencing", "snp", "alteration", "TNF α production", "niche", "analyses", "gene", "murine macrophage cell line", "transmission electron microscopy", "Evo strain", "Single Point Mutation Candida glabrata", "growth form", "phenotype", "cell wall architecture", "Macrophages Renders Candida glabrata Hypervirulent", "mouse infection model", "il", "facs"], "article_id"=>1223414, "categories"=>["Biological Sciences"], "users"=>["Sascha Brunke", "Katja Seider", "Daniel Fischer", "Ilse D. Jacobsen", "Lydia Kasper", "Nadja Jablonowski", "Anja Wartenberg", "Oliver Bader", "Adela Enache-Angoulvant", "Martin Schaller", "Christophe d'Enfert", "Bernhard Hube"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004478.g001", "stats"=>{"downloads"=>2, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Long_term_co_incubation_of_C_glabrata_with_RAW_264_7_macrophages_yields_a_C_glabrata_strain_with_pseudohyphae_like_morphology_/1223414", "title"=>"Long-term co-incubation of <i>C. glabrata</i> with RAW 264.7 macrophages yields a <i>C. glabrata</i> strain with pseudohyphae-like morphology.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-30 03:19:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1772472"], "description"=>"<p>A. Sanger sequencing confirmed the sequence alteration in <i>CHS2</i> of the Evo strain (identified by whole genome sequencing), which led to an Asn→Lys (WT→Evo) amino acid exchange in the protein. Following a counter-selection experiment, the gene reverted to its original sequence (Rev), concomitant with the reversal to the original yeast growth form. B. This single nucleotide exchange observed in of the Evo strain was introduced into the WT strain by PCR amplification of <i>CHS2</i> from the Evo strain, and cotransformation of this fragment with an PCR-amplified <i>HIS3</i> marker including an overlapping (U1) region. C. The resulting strain was called CHS<sup>Evo</sup>, and correct integration was tested by sequencing. Similarly, CHS<sup>WT</sup> was created by amplifying the WT <i>CHS2</i> gene and following the same cloning strategy. D. Morphologies of the WT, Evo, CHS<sup>WT</sup> and CHS<sup>Evo</sup> strain. The introduction of the Evo <i>CHS2</i> gene into CHS<sup>Evo</sup> resulted in a growth form indistinguishable from the original Evo strain. The reintroduction of the WT gene did not change morphology (CHS<sup>WT</sup>).</p>", "links"=>[], "tags"=>["morphology", "chs", "Whole Genome Sequencing", "snp", "alteration", "TNF α production", "niche", "analyses", "gene", "murine macrophage cell line", "transmission electron microscopy", "Evo strain", "Single Point Mutation Candida glabrata", "growth form", "phenotype", "cell wall architecture", "Macrophages Renders Candida glabrata Hypervirulent", "mouse infection model", "il", "facs"], "article_id"=>1223428, "categories"=>["Biological Sciences"], "users"=>["Sascha Brunke", "Katja Seider", "Daniel Fischer", "Ilse D. Jacobsen", "Lydia Kasper", "Nadja Jablonowski", "Anja Wartenberg", "Oliver Bader", "Adela Enache-Angoulvant", "Martin Schaller", "Christophe d'Enfert", "Bernhard Hube"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004478.g007", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_single_nucleotide_exchange_is_sufficient_to_produce_the_evolved_phenotype_/1223428", "title"=>"A single nucleotide exchange is sufficient to produce the evolved phenotype.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-30 03:19:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1772469"], "description"=>"<p>A. Selected cytokines and MPO levels were measured in murine organs at day 2 after infection with wild type or Evo strain. Significantly higher cytokine levels were found specifically in the brain of mice infected with the Evo strain, reflecting the transient high fungal burden in this organ. B. Release of the same cytokines by murine RAW246.7 macrophages was tested for the different strains. Only strains bearing the point mutation in the <i>CHS2</i> gene (Evo and CHS<sup>Evo</sup>) elicited an increased release of TNFα.</p>", "links"=>[], "tags"=>["morphology", "chs", "Whole Genome Sequencing", "snp", "alteration", "TNF α production", "niche", "analyses", "gene", "murine macrophage cell line", "transmission electron microscopy", "Evo strain", "Single Point Mutation Candida glabrata", "growth form", "phenotype", "cell wall architecture", "Macrophages Renders Candida glabrata Hypervirulent", "mouse infection model", "il", "facs"], "article_id"=>1223425, "categories"=>["Biological Sciences"], "users"=>["Sascha Brunke", "Katja Seider", "Daniel Fischer", "Ilse D. Jacobsen", "Lydia Kasper", "Nadja Jablonowski", "Anja Wartenberg", "Oliver Bader", "Adela Enache-Angoulvant", "Martin Schaller", "Christophe d'Enfert", "Bernhard Hube"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004478.g005", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differences_in_the_host_cytokine_response_to_wild_type_and_Evo_strains_in_vivo_and_in_vitro_/1223425", "title"=>"Differences in the host cytokine response to wild type and Evo strains <i>in vivo</i> and <i>in vitro</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-30 03:19:15"}

PMC Usage Stats | Further Information

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