cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.12319646.v2
title: Identification of conditionally essential genes for <i>Streptococcus suis</i> infection in pigs

description: is a Gram-positive bacterium and zoonotic pathogen that causes meningitis and sepsis in pigs and humans. The aim of this study was to identify genes required for <i>S. suis</i> infection. We created Tn-Seq libraries in a virulent <i>S. suis</i> strain 10, which was used to inoculate pigs in an intrathecal experimental infection. Comparative analysis of the relative abundance of mutants recovered from different sites of infection (blood, cerebrospinal fluid, and meninges of the brain) identified 361 conditionally essential genes, i.e. required for infection, which is about 18% of the genome. The conditionally essential genes were primarily involved in metabolic and transport processes, regulation, ribosomal structure and biogenesis, transcription, and cell wall membrane and envelope biogenesis, stress defenses, and immune evasion. Directed mutants were created in a set of 10 genes of different genetic ontologies and their role was determined in <i>ex vivo</i> models. Mutants showed different levels of sensitivity to survival in whole blood, serum, cerebrospinal fluid, thermic shock, and stress conditions, as compared to the wild type. Additionally, the role of three selected mutants was validated in co-infection experiments in which pigs were infected with both wild type and isogenic mutant strains. The genetic determinants of infection identified in this work contribute to novel insights in <i>S. suis</i> pathogenesis and could serve as targets for novel vaccines or antimicrobial drugs.
DOI: 10.6084/m9.figshare.14675598
title: Drone Photographs from the Upper Impoundment 2020-7-10 Flight Date (Dover, NH, USA)

description: These are the raw drone aerial images taken of the upper impoundment area on July 10, 2020 for the Evans et al. Sawyer Mill dam removal study. Alexandra Evans, a certified FAA Part 107 remote pilot, served as the remote pilot in command for the flight mission and was accompanied by a spotter.<br>A DJI Phantom 3 Professional drone was used to take the images, equipped with its original RGB camera and a polarizing filter. Please see the referenced automated flight paths for details on altitude, image overlap, etc. The flight paths were executed using the Litchi flight app.<br>These materials were made using resources from an NSF EPSCoR funded project “RII Track-2 FEC: Strengthening the scientific basis for decision-making about dams: Multi-scale, coupled-systems research on ecological, social, and economic trade-offs” (a.k.a. "Future of Dams"). Support for this project is provided by the National Science Foundation’s Research Infrastructure Improvement NSF #IIA-1539071. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.
DOI: 10.6084/m9.figshare.12319646.v1
title: Identification of conditionally essential genes for <i>Streptococcus suis</i> infection in pigs

description: <i>Streptococcus suis</i> is a Gram-positive bacterium and zoonotic pathogen that causes meningitis and sepsis in pigs and humans. The aim of this study was to identify genes required for <i>S. suis</i> infection. We created Tn-Seq libraries in a virulent <i>S. suis</i> strain 10, which was used to inoculate pigs in an intrathecal experimental infection. Comparative analysis of the relative abundance of mutants recovered from different sites of infection (blood, cerebrospinal fluid, and meninges of the brain) identified 361 conditionally essential genes, i.e. required for infection, which is about 18% of the genome. The conditionally essential genes were primarily involved in metabolic and transport processes, regulation, ribosomal structure and biogenesis, transcription, and cell wall membrane and envelope biogenesis, stress defenses, and immune evasion. Directed mutants were created in a set of 10 genes of different genetic ontologies and their role was determined in <i>ex vivo</i> models. Mutants showed different levels of sensitivity to survival in whole blood, serum, cerebrospinal fluid, thermic shock, and stress conditions, as compared to the wild type. Additionally, the role of three selected mutants was validated in co-infection experiments in which pigs were infected with both wild type and isogenic mutant strains. The genetic determinants of infection identified in this work contribute to novel insights in <i>S. suis</i> pathogenesis and could serve as targets for novel vaccines or antimicrobial drugs.
DOI: 10.6084/m9.figshare.14675598.v1
title: Drone Photographs from the Upper Impoundment 2020-7-10 Flight Date (Dover, NH, USA)

description: These are the raw drone aerial images taken of the upper impoundment area on July 10, 2020 for the Evans et al. Sawyer Mill dam removal study. Alexandra Evans, a certified FAA Part 107 remote pilot, served as the remote pilot in command for the flight mission and was accompanied by a spotter.<br>A DJI Phantom 3 Professional drone was used to take the images, equipped with its original RGB camera and a polarizing filter. Please see the referenced automated flight paths for details on altitude, image overlap, etc. The flight paths were executed using the Litchi flight app.<br>These materials were made using resources from an NSF EPSCoR funded project “RII Track-2 FEC: Strengthening the scientific basis for decision-making about dams: Multi-scale, coupled-systems research on ecological, social, and economic trade-offs” (a.k.a. "Future of Dams"). Support for this project is provided by the National Science Foundation’s Research Infrastructure Improvement NSF #IIA-1539071. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.
DOI: 10.6084/m9.figshare.12852042.v1
title: PE_PGRS proteins of <i>Mycobacterium tuberculosis</i>: A specialized molecular task force at the forefront of host–pathogen interaction

description: To the PE_PGRS protein subfamily belongs a group of surface-exposed mycobacterial antigens that in <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) H37Rv accounts to more than 65 genes, 51 of which are thought to express a functional protein. PE_PGRS proteins share a conserved structural architecture with three main domains: the N-terminal PE domain; the PGRS domain, that can vary in sequence and size and is characterized by the presence of multiple GGA-GGX amino acid repeats; the highly conserved sequence containing the GRPLI motif that links the PE and PGRS domains; the unique C-terminus end that can vary in size from few to up to ≈ 300 amino acids. <i>pe_pgrs</i> genes emerged in slow-growing mycobacteria and expanded and diversified in MTBC and few other pathogenic mycobacteria. Interestingly, despite sequence homology and apparent redundancy, PE_PGRS proteins seem to have evolved a peculiar function. In this review, we summarize the actual knowledge on this elusive protein family in terms of evolution, structure, and function, focusing on the role of PE_PGRS in TB pathogenesis. We provide an original hypothesis on the role of the PE domain and propose a structural model for the polymorphic PGRS domain that might explain how so similar proteins can have different physiological functions.
DOI: 10.6084/m9.figshare.13172679.v1
title: A new regulator in the crossroads of oxidative stress resistance and virulence in <i>Candida glabrata</i>: The transcription factor CgTog1

description: <i>Candida glabrata</i> is a prominent pathogenic yeast which exhibits a unique ability to survive the harsh environment of host immune cells. In this study, we describe the role of the transcription factor encoded by the gene <i>CAGL0F09229g</i>, here named CgTog1 after its <i>Saccharomyces cerevisiae</i> ortholog, as a new determinant of <i>C. glabrata</i> virulence. Interestingly, Tog1 is absent in the other clinically relevant <i>Candida</i> species (<i>C. albicans, C. parapsilosis, C. tropicalis, C. auris</i>), being exclusive to <i>C. glabrata</i>. CgTog1 was found to be required for oxidative stress resistance and for the modulation of reactive oxygen species inside <i>C. glabrata</i> cells. Also, CgTog1 was observed to be a nuclear protein, whose activity up-regulates the expression of 147 genes and represses 112 genes in <i>C. glabrata</i> cells exposed to H<sub>2</sub>O<sub>2</sub>, as revealed through RNA-seq-based transcriptomics analysis. Given the importance of oxidative stress response in the resistance to host immune cells, the effect of <i>CgTOG1</i> expression in yeast survival upon phagocytosis by <i>Galleria mellonella</i> hemocytes was evaluated, leading to the identification of CgTog1 as a determinant of yeast survival upon phagocytosis. Interestingly, CgTog1 targets include many whose expression changes in <i>C. glabrata</i> cells after engulfment by macrophages, including those involved in reprogrammed carbon metabolism, glyoxylate cycle and fatty acid degradation. In summary, CgTog1 is a new and specific regulator of virulence in <i>C. glabrata</i>, contributing to oxidative stress resistance and survival upon phagocytosis by host immune cells.
DOI: 10.6084/m9.figshare.11769915.v1
title: Mutation on <i>lysX</i> from <i>Mycobacterium avium hominissuis</i> impacts the host–pathogen interaction and virulence phenotype

description: The <i>lysX</i> gene from <i>Mycobacterium avium hominissuis</i> (MAH) is not only involved in cationic antimicrobial resistance but also regulates metabolic activity. An MAH <i>lysX</i> deficient mutant was shown to exhibit a metabolic shift at the extracellular state preadapting the bacteria to the conditions inside host-cells. It further showed stronger growth in human monocytes. In the present study, the LysX activity on host–pathogen interactions were analyzed. The lysX mutant from MAH proved to be more sensitive toward host-mediated stresses such as reactive oxygen species. Further, the lysX mutant exhibited increased inflammatory response in PBMC and multinucleated giant cell (MGC) formation in human macrophages during infection studies. Coincidentally, the lysX mutant strain revealed to be more reproductive in the <i>Galleria mellonella</i> infection model. Together, these data demonstrate that LysX plays a role in regulating the bacillary load in host organisms and the lack of <i>lys</i> <i>X</i> gene facilitates MAH adaptation to intracellular host-habitat, thereby suggesting an essential role of LysX in the modulation of host–pathogen interaction.
DOI: 10.6084/m9.figshare.12309824.v2
title: Relevance of inducible nitric oxide synthase for immune control of <i>Mycobacterium avium</i> subspecies <i>paratuberculosis</i> infection in mice

description: subspecies <i>paratuberculosis</i> (MAP) causes Johne’s disease (JD), an incurable chronic intestinal bowel disease in ruminants. JD occurs worldwide and causes enormous economic burden in dairy industry. Research on JD pathobiology is hampered by its complexity which cannot completely be mimicked by small animal models. As a model the mouse allows dissecting some pathogenicity features of MAP. However, for unknown reasons MAP exhibits reduced growth in granulomas of infected mice compared to other <i>Mycobacterium avium</i> subspecies. Here, we characterized immune reactions of MAP-infected C57BL/6 mice. After infection, mice appeared fully immunocompetent. A strong antigen-specific T cell response was elicited indicated by IFNγ production of splenic T cells re-stimulated with MAP antigens. Function of splenic dendritic cells and proliferation of adoptively transferred antigen-specific CD4<sup>+</sup> T cells was unaltered. Isolated splenic myeloid cells from infected mice revealed that MAP resides in CD11b<sup>+</sup> macrophages. Importantly, sorted CD11b<sup>+</sup>CD11c<sup>−</sup> cells expressed high level of type 2 nitric oxide synthase (NOS2) but only low levels of pro- and anti-inflammatory cytokines. Correspondingly, MAP-infected MAC2 expressing myeloid cells in spleen and liver granuloma displayed strong expression of NOS2. In livers of infected <i>Nos2<sup>−/−</sup> </i>mice higher bacterial loads, more granuloma and larger areas of tissue damage were observed 5 weeks post infection compared to wild type mice. <i>In vitro</i>, MAP was sensitive to NO released by a NO-donor. Thus, a strong T cell response and concomitant NOS2/NO activity appears to control MAP infection, but allows development of chronicity and pathogen persistence. A similar mechanism might explain persistence of MAP in ruminants.
DOI: 10.6084/m9.figshare.12309824.v1
title: Relevance of inducible nitric oxide synthase for immune control of <i>Mycobacterium avium</i> subspecies <i>paratuberculosis</i> infection in mice

description: <i>Mycobacterium avium</i> subspecies <i>paratuberculosis</i> (MAP) causes Johne’s disease (JD), an incurable chronic intestinal bowel disease in ruminants. JD occurs worldwide and causes enormous economic burden in dairy industry. Research on JD pathobiology is hampered by its complexity which cannot completely be mimicked by small animal models. As a model the mouse allows dissecting some pathogenicity features of MAP. However, for unknown reasons MAP exhibits reduced growth in granulomas of infected mice compared to other <i>Mycobacterium avium</i> subspecies. Here, we characterized immune reactions of MAP-infected C57BL/6 mice. After infection, mice appeared fully immunocompetent. A strong antigen-specific T cell response was elicited indicated by IFNγ production of splenic T cells re-stimulated with MAP antigens. Function of splenic dendritic cells and proliferation of adoptively transferred antigen-specific CD4<sup>+</sup> T cells was unaltered. Isolated splenic myeloid cells from infected mice revealed that MAP resides in CD11b<sup>+</sup> macrophages. Importantly, sorted CD11b<sup>+</sup>CD11c<sup>−</sup> cells expressed high level of type 2 nitric oxide synthase (NOS2) but only low levels of pro- and anti-inflammatory cytokines. Correspondingly, MAP-infected MAC2 expressing myeloid cells in spleen and liver granuloma displayed strong expression of NOS2. In livers of infected <i>Nos2<sup>−/−</sup></i>mice higher bacterial loads, more granuloma and larger areas of tissue damage were observed 5 weeks post infection compared to wild type mice. <i>In vitro</i>, MAP was sensitive to NO released by a NO-donor. Thus, a strong T cell response and concomitant NOS2/NO activity appears to control MAP infection, but allows development of chronicity and pathogen persistence. A similar mechanism might explain persistence of MAP in ruminants.
DOI: 10.6084/m9.figshare.12852036.v1
title: Transcriptional host–pathogen responses of <i>Pseudogymnoascus destructans</i> and three species of bats with white-nose syndrome

description: Understanding how context (e.g., host species, environmental conditions) drives disease susceptibility is an essential goal of disease ecology. We hypothesized that in bat white-nose syndrome (WNS), species-specific host–pathogen interactions may partly explain varying disease outcomes among host species. We characterized bat and pathogen transcriptomes in paired samples of lesion-positive and lesion-negative wing tissue from bats infected with <i>Pseudogymnoascus destructans</i> in three parallel experiments. The first two experiments analyzed samples collected from the susceptible Nearctic <i>Myotis lucifugus</i> and the less-susceptible Nearctic <i>Eptesicus fuscus</i>, following experimental infection and hibernation in captivity under controlled conditions. The third experiment applied the same analyses to paired samples from infected, free-ranging <i>Myotis myotis</i>, a less susceptible, Palearctic species, following natural infection and hibernation (n = 8 sample pairs/species). Gene expression by <i>P. destructans</i> was similar among the three host species despite varying environmental conditions among the three experiments and was similar within each host species between saprophytic contexts (superficial growth on wings) and pathogenic contexts (growth in lesions on the same wings). In contrast, we observed qualitative variation in host response: <i>M. lucifugus</i> and <i>M. myotis</i> exhibited systemic responses to infection, while <i>E. fuscus</i> up-regulated a remarkably localized response. Our results suggest potential phylogenetic determinants of response to WNS and can inform further studies of context-dependent host–pathogen interactions.
DOI: 10.6084/m9.figshare.13359907.v1
title: Virulence role of the outer membrane protein CarO in carbapenem-resistant <i>Acinetobacter baumannii</i>

description: Novel approaches to treat carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB) infections are urgently needed and anti-virulence drugs represent promising alternatives, but our knowledge on potential targets is scarce. We searched for potential <i>A. baumannii</i> virulence factors by whole-genome sequencing-based comparisons of CRAB clinical isolates causing bloodstream infections secondary to ventilator-associated pneumonia from demographics and clinically homogeneous patients, who received optimal treatment but with different clinical outcomes. Thus, the <i>carO</i> gene was interrupted in CRAB isolates from surviving patients, while it was intact in isolates from non-surviving patients, and proteomic/immunoblot techniques corroborated it. When the virulence role of <i>A. baumannii</i> CarO was analyzed in model systems, isogenic Δ<i>carO</i> mutants and a CRAB clinical isolate with truncated CarO, showed lower ability to adhere and invade A549 cells and <i>in vivo</i> virulence. This unnoticed virulence role for CarO postulate this <i>A. baumannii</i> outer membrane protein as a potential target for new therapies against CRAB infections.
DOI: 10.6084/m9.figshare.12091419.v1
title: Direct interaction between RecA and a CheW-like protein is required for surface-associated motility, chemotaxis and the full virulence of <i>Acinetobacter baumannii</i> strain ATCC 17978

description: <i>Acinetobacter baumannii</i> is a nosocomial pathogen that causes multi-drug resistant infections mainly in immunocompromised patients. Although this gram-negative species lacks flagella, it is able to move over wet surfaces through a not well characterized type of movement known as surface-associated motility. In this study we demonstrate through the inactivation of the <i>A1S_2813</i> gene (coding a CheW-like protein) and <i>recA</i> (coding a DNA damage repair and recombination protein) that both genes are involved in the surface-associated motility and chemotaxis of <i>A. baumannii</i> ATCC 17978 strain. In addition, we also point out that the lack of either RecA or CheW-like proteins reduces its virulence in the <i>Caenorhabditis elegans</i> and the <i>Galleria mellonella</i> animal models. Furthermore, we show through co-immunoprecipitation assays that the CheW-like protein and RecA interact and that this interaction is abolished by the introduction of the mutation S97A in one of the domains of CheW-like protein that is structurally conserved in <i>Salmonella enterica</i> and necessary for the RecA-CheW interaction in this bacterial species. Finally, we show that the replacement of the wild-type CheW-like protein by that presenting the S97A mutation impairs surface-associated motility, chemotaxis and virulence of <i>A. baumannii</i> strain ATCC 17978.
DOI: 10.6084/m9.figshare.13003591.v1
title: <i>Coxiella burnetii</i> replicates in <i>Galleria mellonella</i> hemocytes and transcriptome mapping reveals <i>in vivo</i> regulated genes

description: Larvae of the greater wax moth (<i>Galleria mellonella)</i> are susceptible to infection with <i>C. burnetii</i>, an obligate intracellular bacterial pathogen. We show that bacteria are found in hemocytes after infection, and occupy vacuoles which are morphologically similar to <i>Coxiella</i>-containing vacuoles seen in infected mammalian phagocytes. We characterized the infection by transcriptome profiling of bacteria isolated from the hemocytes of infected larvae and identified 46 highly upregulated genes. The encoded proteins are predicted to be involved in translation, LPS biosynthesis, biotin synthesis, scavenging of reactive oxygen species, and included a T4SS effector and 30 hypothetical proteins. Some of these genes had previously been shown to be upregulated in buffalo green monkey (BGM) cells or in mice, whilst others appear to be regulated in a host-specific manner. Altogether, our results demonstrate the value of the <i>G. mellonella</i> model to study intracellular growth and identify potential virulence factors of <i>C. burnetii</i>.
DOI: 10.6084/m9.figshare.12852015.v1
title: Contribution of NKT cells to the immune response and pathogenesis triggered by respiratory viruses

description: Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) cause acute respiratory tract infections in children worldwide. Natural killer T (NKT) cells are unconventional T lymphocytes, and their TCRs recognize glycolipids bound to the MHC-I-like molecule, CD1d. These cells modulate the inflammatory response in viral infections. Here, we evaluated the contribution of NKT cells in both hRSV and hMPV infections. A significant decrease in the number of neutrophils, eosinophils, and CD103<sup>+</sup>DCs infiltrating to the lungs, as well as an increased production of IFN-γ, were observed upon hRSV-infection in CD1d-deficient BALB/c mice, as compared to wild-type control mice. However, this effect was not observed in the CD1d-deficient BALB/c group, upon infection with hMPV. Importantly, reduced expression of CD1d in CD11b<sup>+</sup> DCs and epithelial cells was found in hRSV -but not hMPV-infected mice. Besides, a reduction in the expression of CD1d in alveolar macrophages of lungs from hRSV- and hMPV-infected mice was found. Such reduction of CD1d expression interfered with NKT cells activation, and consequently IL-2 secretion, as characterized by <i>in vitro</i> experiments for both hRSV and hMPV infections. Furthermore, increased numbers of NKT cells recruited to the lungs in response to hRSV- but not hMPV-infection was detected, resulting in a reduction in the expression of IFN-γ and IL-2 by these cells. In conclusion, both hRSV and hMPV might be differently impairing NKT cells function and contributing to the immune response triggered by these viruses.
DOI: 10.6084/m9.figshare.13078725.v1
title: Proteome analysis of bronchoalveolar lavage fluids reveals host and fungal proteins highly expressed during invasive pulmonary aspergillosis in mice and humans

description: Invasive pulmonary aspergillosis (IPA) is a severe infection that is difficult to diagnose due to the ubiquitous presence of fungal spores, the underlying diseases of risk patients, and limitations of currently available markers. In this study, we performed a comprehensive liquid chromatography tandem mass spectrometry (LC-MS/MS)-based identification of host and fungal proteins expressed during IPA in mice and humans. The proteomic analysis of bronchoalveolar lavage samples of individual IPA and control cases allowed the description of common host factors that had significantly increased abundance in both infected animals and IPA patients compared to their controls. Although increased levels of these individual host proteins might not be sufficient to distinguish bacterial from fungal infection, a combination of these markers might be beneficial to improve diagnosis. We also identified 16 fungal proteins that were specifically detected during infection and may be valuable candidates for biomarker evaluation.