GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Construction of short tandem target mimic (STTM) to block the functions of plant and animal microRNAs
    Elsevier BV ; 2012
    In:  Methods Vol. 58, No. 2 ( 2012-10), p. 118-125
    Details
    In: Methods, Elsevier BV, Vol. 58, No. 2 ( 2012-10), p. 118-125
    Type of Medium: Online Resource
    ISSN: 1046-2023
    URL: Article
    DOI: 10.1016/j.ymeth.2012.10.006
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2012
    detail.hit.zdb_id: 1471152-7
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Combination treatment of liposomal amphotericin B and isavuconazole is synergistic in treating experimental mucormycosis
    Oxford University Press (OUP) ; 2021
    In:  Journal of Antimicrobial Chemotherapy Vol. 76, No. 10 ( 2021-09-15), p. 2636-2639
    Details
    In: Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), Vol. 76, No. 10 ( 2021-09-15), p. 2636-2639
    Abstract: Liposomal amphotericin B (L-AMB) and isavuconazonium sulphate are commonly used antifungal drugs to treat mucormycosis. However, the efficacy of combination therapy of L-AMB/isavuconazonium sulphate versus monotherapy is unknown. We used an immunosuppressed mouse model of pulmonary mucormycosis to compare the efficacy of L-AMB/isavuconazonium sulphate versus either drug alone. Methods Neutropenic mice were intratracheally infected with either Rhizopus delemar or Mucor circinelloides. Treatment with L-AMB, isavuconazonium sulphate, or a combination of both started 8 h post-infection and continued through to Day +4. Placebo mice received vehicle control. Survival to Day +21 and tissue fungal burden (by conidial equivalent using quantitative PCR) on Day +4, served as primary and secondary endpoints, respectively. Results For mice infected with R. delemar, L-AMB and isavuconazonium sulphate equally prolonged median survival time and enhanced survival versus placebo (an overall survival of 50% for either drug alone, versus 5% for placebo). Importantly, combination treatment resulted in an overall survival of 80%. Both antifungal drugs reduced tissue fungal burden of lungs and brain by ∼1.0–2.0 log versus placebo-treated mice. Treatment with combination therapy resulted in 2.0–3.5 log reduction in fungal burden of either organ versus placebo and 1.0 log reduction versus either drug alone. Similar treatment outcomes were obtained using mice infected with M. circinelloides. Conclusions The L-AMB/isavuconazonium sulphate combination demonstrated greater activity versus monotherapy in immunosuppressed mice infected with either of the two most common causes of mucormycosis. These studies warrant further investigation of L-AMB/isavuconazonium sulphate combination therapy as an optimal therapy of human mucormycosis.
    Type of Medium: Online Resource
    ISSN: 0305-7453 , 1460-2091
    URL: Article
    DOI: 10.1093/jac/dkab233
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1467478-6
    SSG: 15,3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    119. A Humanized Antibody Targeting the CotH Invasins is Protective Against Murine Mucormycosis
    Oxford University Press (OUP) ; 2021
    In:  Open Forum Infectious Diseases Vol. 8, No. Supplement_1 ( 2021-12-04), p. S71-S72
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. Supplement_1 ( 2021-12-04), p. S71-S72
    Abstract: Despite antifungal therapy and surgical debridement, overall mortality of invasive mucormycosis is & gt;40%. Currently the world is witnessing an explosion in mucormycosis in India among COVID-19 patients with an official count of 28,252 cases as of 06/07/2021. Thus, novel therapeutic modalities are needed. We previously reported on a mouse monoclonal antibody (C2) targeting CotH invasins being protective against mucormycosis. Here, we humanized C2 MAb and assessed its efficacy in vitro and in vivo. Methods The C2 (IgG1) paratopes of the heavy chain and light chain were grafted on the most suitable human IgG1 with back mutations in the paratopes needed to restore binding of humanized clones to CotH3 (by biolayer interferometry using Gator). Clones were compared to C2 in their ability to prevent Rhizopus delemar-induced injury to A549 alveolar epithelial and primary human endothelial cells and for enhancing human neutrophil killing of the fungus in vitro. C2 and the humanized clones were also compared for their ability to protect neutropenic mice from mucormycosis induced by R. delemar or Mucor cicrinelloides with and without antifungal therapy. Results Three humanized clones showed 10-fold enhanced binding affinity to CotH3 protein (~5 nM for humanized vs. ~50 nM for C2). One humanized clone (VX01) doubled the ability of neutrophils to kill R. delemar and resulted in ~50% reduction in host cell damage. A single low dose of VX01 (30 µg) given 24 h post infection resulted in comparable survival of 60-70% in mice infected intratracheally with either R. delemar or M. cicrinelloides vs. placebo mice (0% survival, P & lt; 0.02). Importantly, VX01 acted synergistically in protecting mice when combined with liposomal amphotericin B or posaconazole in a severe model of mucormycosis with treatment starting 48 h post infection (~70% survival for combination vs. 0-20% survival for monotherapy and reduced lung fungal burden by 1.5 log, P & lt; 0.001). GLP-tissue cross reactivity studies of VX01 showed favorable safety profiles. Conclusion VX01 shows enhanced binding to CotH3 protein and maintained the protective features of C2 MAb against murine mucormycosis. Clinical testing of combination therapy of VX01 + antifungals is warranted. VX01 is currently in manufacturing. Disclosures Yiyou Gu, PhD, Vitalex Biosciences (Shareholder) Ashraf S. Ibrahim, PhD, Vitalex Biosciences (Shareholder)
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofab466.119
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2757767-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    678. Galactomannan Is a Biomarker of APX001 (Fosmanogepix) Efficacy in Treating Experimental Invasive Pulmonary Aspergillosis
    Oxford University Press (OUP) ; 2019
    In:  Open Forum Infectious Diseases Vol. 6, No. Supplement_2 ( 2019-10-23), p. S309-S309
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 6, No. Supplement_2 ( 2019-10-23), p. S309-S309
    Abstract: Invasive pulmonary aspergillosis (IPA) is a serious fungal infection afflicting immunocompromised patients. Galactomannan (GM) detection in biological samples using the Platelia ELISA has been shown to predict therapy response by azoles, and polyenes. We previously reported on the activity of APX001 (fosmanogepix) in treating murine IPA. Here, we investigated the potential use of GM as a biomarker of APX001 efficacy in an immunosuppressed murine model of IPA. Methods ICR mice (n = 8/group) were immunosuppressed with cyclophosphamide and cortisone acetate on days −2, and +3, relative to infection with Aspergillus fumigatus via inhalation. Treatment with placebo (diluent control), APX001 (104 mg/kg, PO, a human equivalent dose), or posaconazole (POSA, 30 mg/kg, BID [equivalent to 6× the humanized dose]) began 16-hour post-infection and continued daily. To extend the half-life of APX001, mice were administered 50 mg/kg of the cytochrome P450 inhibitor 1-aminobenzotriazole (ABT) 2 hours prior to APX001 administration. Mice were sacrificed 48-, 72-, or 96-hour post-infection and their lungs, bronchoalveolar lavage (BAL) and sera were collected. Lung fungal burden was determined by conidial equivalent (CE) using qPCR, while GM was determined using the Platelia ELISA. Results Compared with placebo, APX001 or POSA treatment resulted in a gradual decrease in tissue fungal burden over time with APX001 or POSA showing significant reduction as early as 96 and 72 hours, respectively (P & lt; 0.005). Although the super-therapeutic dose of POSA resulted in faster reduction in lung fungal burden after 72 hours, both drugs resulted in similar reduction (~6–7 log) in lung CE vs. placebo after 96 hours. Changes in GM levels in BAL or serum samples mirrored reductions in lung CFU with significant decrease seen after 96 hours or 72 hours for APX001 or POSA, respectively, vs. placebo (P & lt; 0.02) (figure). Conclusion A human equivalent dose of APX001 and a super humanized dose of POSA resulted in a time-dependent reduction of lung fungal burden and GM levels when compared with placebo. These results show that GM can be used as a biomarker of APX001 efficacy in immunosuppressed mice. Disclosures All authors: No reported disclosures.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofz360.746
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2757767-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    PCR-Based Approach Targeting Mucorales-Specific Gene Family for Diagnosis of Mucormycosis
    American Society for Microbiology ; 2018
    In:  Journal of Clinical Microbiology Vol. 56, No. 10 ( 2018-10)
    Details
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 56, No. 10 ( 2018-10)
    Abstract: Mucormycosis is an aggressive, life-threatening infection caused by fungi in the order Mucorales. The current diagnosis of mucormycosis relies on mycological cultures, radiology and histopathology. These methods lack sensitivity and are most definitive later in the course of infection, resulting in the prevention of timely intervention. PCR-based approaches have shown promising potential in rapidly diagnosing mucormycosis. The spore coating protein homolog encoding CotH genes are uniquely and universally present among Mucorales. Thus, CotH genes are potential targets for the rapid diagnosis of mucormycosis. We infected mice with different Mucorales known to cause human mucormycosis and investigated whether CotH could be PCR amplified from biological fluids. Uninfected mice and those with aspergillosis were used to determine the specificity of the assay. CotH was detected as early as 24 h postinfection in plasma, urine, and bronchoalveolar lavage (BAL) samples from mice infected intratracheally with Rhizopus delemar , Rhizopus oryzae , Mucor circinelloides , Lichtheimia corymbifera , or Cunninghamella bertholletiae but not from samples taken from uninfected mice or mice infected with Aspergillus fumigatus . Detection of CotH from urine samples was more reliable than from plasma or BAL fluid. Using the receiver operating characteristic method, the sensitivity and the specificity of the assay were found to be 90 and 100%, respectively. Finally, CotH was PCR amplified from urine samples of patients with proven mucormycosis. Thus, PCR amplification of CotH is a promising target for the development of a reliable, sensitive, and simple method of early diagnosis of mucormycosis.
    Type of Medium: Online Resource
    ISSN: 0095-1137 , 1098-660X
    URL: Article
    DOI: 10.1128/JCM.00746-18
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2018
    detail.hit.zdb_id: 1498353-9
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    A Resource for Inactivation of MicroRNAs Using Short Tandem Target Mimic Technology in Model and Crop Plants
    Elsevier BV ; 2018
    In:  Molecular Plant Vol. 11, No. 11 ( 2018-11), p. 1400-1417
    Details
    In: Molecular Plant, Elsevier BV, Vol. 11, No. 11 ( 2018-11), p. 1400-1417
    Type of Medium: Online Resource
    ISSN: 1674-2052
    URL: Article
    DOI: 10.1016/j.molp.2018.09.003
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 2393618-6
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Functional plasticity of miR165/166 in plant development revealed by small tandem target mimic
    Elsevier BV ; 2015
    In:  Plant Science Vol. 233 ( 2015-04), p. 11-21
    Details
    In: Plant Science, Elsevier BV, Vol. 233 ( 2015-04), p. 11-21
    Type of Medium: Online Resource
    ISSN: 0168-9452
    URL: Article
    DOI: 10.1016/j.plantsci.2014.12.020
    RVK:
    WA 15000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
    detail.hit.zdb_id: 1498605-X
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    GRP78 and Integrins Play Different Roles in Host Cell Invasion during Mucormycosis
    American Society for Microbiology ; 2020
    In:  mBio Vol. 11, No. 3 ( 2020-06-30)
    Details
    In: mBio, American Society for Microbiology, Vol. 11, No. 3 ( 2020-06-30)
    Abstract: Mucormycosis, caused by Rhizopus species, is a life-threatening fungal infection that occurs in patients immunocompromised by diabetic ketoacidosis (DKA), cytotoxic chemotherapy, immunosuppressive therapy, hematologic malignancies, or severe trauma. Inhaled Rhizopus spores cause pulmonary infections in patients with hematologic malignancies, while patients with DKA are much more prone to rhinoorbital/cerebral mucormycosis. Here, we show that Rhizopus delemar interacts with glucose-regulated protein 78 (GRP78) on nasal epithelial cells via its spore coat protein CotH3 to invade and damage the nasal epithelial cells. Expression of the two proteins is significantly enhanced by high glucose, iron, and ketone body levels (hallmark features of DKA), potentially leading to frequently lethal rhinoorbital/cerebral mucormycosis. In contrast, R. delemar CotH7 recognizes integrin β1 as a receptor on alveolar epithelial cells, causing the activation of epidermal growth factor receptor (EGFR) and leading to host cell invasion. Anti-integrin β1 antibodies inhibit R. delemar invasion of alveolar epithelial cells and protect mice from pulmonary mucormycosis. Our results show that R. delemar interacts with different mammalian receptors depending on the host cell type. Susceptibility of patients with DKA primarily to rhinoorbital/cerebral disease can be explained by host factors typically present in DKA and known to upregulate CotH3 and nasal GRP78, thereby trapping the fungal cells within the rhinoorbital milieu, leading to subsequent invasion and damage. Our studies highlight that mucormycosis pathogenesis can potentially be overcome by the development of novel customized therapies targeting niche-specific host receptors or their respective fungal ligands. IMPORTANCE Mucormycosis caused by Rhizopus species is a fungal infection with often fatal prognosis. Inhalation of spores is the major route of entry, with nasal and alveolar epithelial cells among the first cells that encounter the fungi. In patients with hematologic malignancies or those undergoing cytotoxic chemotherapy, Rhizopus causes pulmonary infections. On the other hand, DKA patients predominantly suffer from rhinoorbital/cerebral mucormycosis. The reason for such disparity in disease types by the same fungus is not known. Here, we show that the unique susceptibility of DKA subjects to rhinoorbital/cerebral mucormycosis is likely due to specific interaction between nasal epithelial cell GRP78 and fungal CotH3, the expression of which increases in the presence of host factors present in DKA. In contrast, pulmonary mucormycosis is initiated via interaction of inhaled spores expressing CotH7 with integrin β1 receptor, which activates EGFR to induce fungal invasion of host cells. These results introduce a plausible explanation for disparate disease manifestations in DKA versus those in hematologic malignancy patients and provide a foundation for development of therapeutic interventions against these lethal forms of mucormycosis.
    Type of Medium: Online Resource
    ISSN: 2161-2129 , 2150-7511
    URL: Article
    DOI: 10.1128/mBio.01087-20
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2020
    detail.hit.zdb_id: 2557172-2
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    An evolutionarily diverged mitochondrial protein controls biofilm growth and virulence in Candida albicans
    Public Library of Science (PLoS) ; 2021
    In:  PLOS Biology Vol. 19, No. 3 ( 2021-3-15), p. e3000957-
    Details
    In: PLOS Biology, Public Library of Science (PLoS), Vol. 19, No. 3 ( 2021-3-15), p. e3000957-
    Abstract: A forward genetic screening approach identified orf19.2500 as a gene controlling Candida albicans biofilm dispersal and biofilm detachment. Three-dimensional (3D) protein modeling and bioinformatics revealed that orf19.2500 is a conserved mitochondrial protein, structurally similar to, but functionally diverged from, the squalene/phytoene synthases family. The C . albicans orf19.2500 is distinguished by 3 evolutionarily acquired stretches of amino acid inserts, absent from all other eukaryotes except a small number of ascomycete fungi. Biochemical assays showed that orf19.2500 is required for the assembly and activity of the N A D H u biquinone oxidoreductase Complex I (CI) of the respiratory electron transport chain (ETC) and was thereby named NDU1 . NDU1 is essential for respiration and growth on alternative carbon sources, important for immune evasion, required for virulence in a mouse model of hematogenously disseminated candidiasis, and for potentiating resistance to antifungal drugs. Our study is the first report on a protein that sets the Candida -like fungi phylogenetically apart from all other eukaryotes, based solely on evolutionary “gain” of new amino acid inserts that are also the functional hub of the protein.
    Type of Medium: Online Resource
    ISSN: 1545-7885
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.1371/journal.pbio.3000957
    DOI: 10.1371/journal.pbio.3000957.g001
    DOI: 10.1371/journal.pbio.3000957.g002
    DOI: 10.1371/journal.pbio.3000957.g003
    DOI: 10.1371/journal.pbio.3000957.g004
    DOI: 10.1371/journal.pbio.3000957.g005
    DOI: 10.1371/journal.pbio.3000957.g006
    DOI: 10.1371/journal.pbio.3000957.g007
    DOI: 10.1371/journal.pbio.3000957.s001
    DOI: 10.1371/journal.pbio.3000957.s002
    DOI: 10.1371/journal.pbio.3000957.s003
    DOI: 10.1371/journal.pbio.3000957.s004
    DOI: 10.1371/journal.pbio.3000957.s005
    DOI: 10.1371/journal.pbio.3000957.s006
    DOI: 10.1371/journal.pbio.3000957.s007
    DOI: 10.1371/journal.pbio.3000957.s008
    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2021
    detail.hit.zdb_id: 2126773-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Preserving Vascular Integrity Protects Mice against Multidrug-Resistant Gram-Negative Bacterial Infection
    American Society for Microbiology ; 2020
    In:  Antimicrobial Agents and Chemotherapy Vol. 64, No. 8 ( 2020-07-22)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 64, No. 8 ( 2020-07-22)
    Abstract: The rise in multidrug-resistant (MDR) organisms portends a serious global threat to the health care system with nearly untreatable infectious diseases, including pneumonia and its often fatal sequelae, acute respiratory distress syndrome (ARDS) and sepsis. Gram-negative bacteria (GNB), including Acinetobacter baumannii , Pseudomonas aeruginosa , and carbapenemase-producing Klebsiella pneumoniae (CPKP), are among the World Health Organization’s and National Institutes of Health’s high-priority MDR pathogens for targeted development of new therapies. Here, we show that stabilizing the host’s vasculature by genetic deletion or pharmacological inhibition of the small GTPase ADP-ribosylation factor 6 (ARF6) increases survival rates of mice infected with A. baumannii , P. aeruginosa , and CPKP. We show that the pharmacological inhibition of ARF6-GTP phenocopies endothelium-specific Arf6 disruption in enhancing the survival of mice with A. baumannii pneumonia, suggesting that inhibition is on target. Finally, we show that the mechanism of protection elicited by these small-molecule inhibitors acts by the restoration of vascular integrity disrupted by GNB lipopolysaccharide (LPS) activation of the TLR4/MyD88/ARNO/ARF6 pathway. By targeting the host’s vasculature with small-molecule inhibitors of ARF6 activation, we circumvent microbial drug resistance and provide a potential alternative/adjunctive treatment for emerging and reemerging pathogens.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00303-20
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2020
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...