Article
Microbiology
Mario Aguiar, Thomas Orasch, Matthias Misslinger, Anna-Maria Dietl, Fabio Gsaller, Hubertus Haas
Summary: The study characterized siderophore use by Aspergillus fumigatus and substrate characteristics of Sit1 and Sit2, revealing the diversity and differences in siderophore transport in the pathogen, providing further insights into the mechanisms of siderophores in host pathogens.
Article
Microbiology
Jing Ye, Yamei Wang, Xinyu Li, Qinyi Wan, Yuanwei Zhang, Ling Lu
Summary: Millions of immunocompromised people are at a higher risk of developing severe fungal diseases. The limited number of antifungals and the emergence of antimicrobial resistance call for new strategies against invasive fungal infections. This study demonstrates that calcium supplementation combined with iron deficiency inhibits the growth of human fungal pathogens, including Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans. Iron deficiency induces a nonspecific calcium uptake response, leading to toxic levels of metal. The findings suggest that a microenvironment with excess calcium and limited iron is an efficient strategy to curb the growth of fungal pathogens, especially for drug-resistant isolates.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Matthew R. Breuer, Ananya Dasgupta, Joseph G. Vasselli, Xiaorong Lin, Brian D. Shaw, Matthew S. Sachs
Summary: The prevalence and increasing incidence of fungal infections globally is a significant worldwide health problem. Cryptococcosis, primarily caused by the pathogenic yeast Cryptococcus neoformans, is responsible for approximatelyestimated deaths annually. The scarcity of treatments and the increasing resistance to current therapeutics highlight the need for the development of antifungal agents which have novel mechanisms of action and are suitable for clinical use. Repurposing existing FDA-approved compounds as antimycotic therapeutics is a promising strategy for the rapid development of such new treatments. Sertraline (SRT), a commonly prescribed antidepressant, is a broad-spectrum antifungal agent with particular efficacy against C. neoformans. However, the effect of SRT on fungal physiology is not understood. Here, we report that SRT induces the formation of supersized lipid droplets (SLDs) in C. neoformans, and in Candida albicans, Saccharomyces cerevisiae, and Aspergillus fumigatus. SLDs were not induced in C. neoformans by treatment with the antifungal fluconazole (FLC), consistent with SRT and FLC acting differently to perturb C. neoformans physiology. The formation of SLDs in response to SRT indicates that this compound alters the lipid metabolism of C. neoformans. Moreover, the SRT-induced enlargement of LDs in other fungal species may indicate a common fungal response to SRT.
Article
Microbiology
Annie Yap, Ricarda Volz, Sanjoy Paul, W. Scott Moye-Rowley, Hubertus Haas
Summary: Iron acquisition is crucial for the virulence of Aspergillus fumigatus. AtrR, in cooperation with SrbA, is involved in the transcriptional activation of iron uptake, in addition to SreA. Functional sequences resembling binding motifs for SrbA, SreA, and AtrR were identified in the promoter of the iron permease-encoding gene, ftrA. This study emphasizes the direct involvement of SrbA, AtrR, and SreA in iron regulation and highlights the coordination of iron homeostasis with biosynthesis of ergosterol and heme as well as adaptation to hypoxia.
Article
Microbiology
Nivea Pereira de Sa, Kalani Jayanetti, Dominick Rendina, Timothy Clement, Veronica Soares Brauer, Caroline Mota Fernandes, Iwao Ojima, Michael V. Airola, Maurizio Del Poeta
Summary: Invasive fungal infections are a leading cause of death in immunocompromised patients. We studied the fungus-specific enzyme SglA as a therapeutic target and identified selective inhibitors that delay filamentation in the pathogenic fungus and increase survival in a murine model of pulmonary aspergillosis.
Article
Microbiology
Oliver Bader
Summary: The study evaluated the usefulness of the commonly used csp1 marker for resistance detection and epidemiologic stratification among A. fumigatus isolates. While the distribution of csp1 types mostly correlates with A. fumigatus population structure and is meaningful for narrowly defined cases of azole resistance phenotypes, outcrossing of csp1 into other clades is also observed.
MICROBIOLOGY SPECTRUM
(2021)
Article
Microbiology
Jennifer Scott, Clara Valero, Alvaro Mato-Lopez, Ian J. Donaldson, Alejandra Roldan, Harry Chown, Norman Van Rhijn, Rebeca Lobo-Vega, Sara Gago, Takanori Furukawa, Alma Morogovsky, Ronen Ben Ami, Paul Bowyer, Nir Osherov, Thierry Fontaine, Gustavo H. Goldman, Emilia Mellado, Michael Bromley, Jorge Amich
Summary: Aspergillus fumigatus, a filamentous fungus, can infect the lungs of immunosuppressed and/or patients with underlying lung diseases. Resistance to the first-line antifungal drugs, azoles, has emerged and spread, leading to higher mortality and reduced treatment options. Treatment failure is also common in patients infected with susceptible isolates, which may be due to poor drug absorption. Persistence to voriconazole, a first-line antifungal, has been observed in some A. fumigatus isolates, which reduces treatment efficacy and has a distinct transcriptional profile. This study highlights the importance of azole persistence in influencing the outcome of human aspergillosis.
MICROBIOLOGY SPECTRUM
(2023)
Article
Immunology
Houda Snen, Aicha Kallel, Hana Blibech, Sana Jemel, Nozha Ben Salah, Sonia Marouen, Nadia Mehiri, Slah Belhaj, Bechir Louzir, Kalthoum Kallel
Summary: ABPA is an immunological pulmonary disorder caused by hypersensitivity to Aspergillus, difficult to diagnose and commonly treated with inhaled therapy and oral corticosteroids. Symptoms improved in the patient but relapsed during tapering of corticosteroids.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Sebastian Schruefer, Isabella Boehmer, Karl Dichtl, Anja Spadinger, Christoph Kleinemeier, Frank Ebel
Summary: The study found that the antifungal activity of fludioxonil in A. fumigatus relies on two distinct and synergistic processes: a high internal osmotic pressure and a weakened cell wall. Skn7's involvement in both processes most likely accounts for its particular importance in the antifungal activity of fludioxonil.
SCIENTIFIC REPORTS
(2021)
Review
Microbiology
Karen Joy Shaw
Summary: GR-2397 is a novel antifungal agent for the treatment of invasive aspergillosis. It shows high efficacy against various fungi and has a favorable safety and tolerability profile. Further development of GR-2397 is warranted based on its promising characteristics.
Article
Microbiology
Hamid Badali, Connie Canete-Gibas, Dora McCarthy, Hoja Patterson, Carmita Sanders, Marjorie P. David, James Mele, Hongxin Fan, Nathan P. Wiederhold
Summary: Aspergillus fumigatus is the most prevalent species causing infections in the United States, and there is growing concern about resistance to azole drugs. This study evaluated the distribution and susceptibility profiles of isolates within Aspergillus section Fumigati, finding that most isolates were susceptible to antifungal drugs, but mutations associated with azole resistance were present in a significant proportion of resistant isolates.
JOURNAL OF CLINICAL MICROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Stephanie Nguyen, Jia Q. Truong, John B. Bruning
Summary: Invasive fungal infections pose a serious threat to human health, necessitating the development of novel antifungal drugs. Targeted interruption of essential metabolic pathways in fungi shows promise as a strategy to disrupt fungal survival and virulence.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Microbiology
Jorge Amich
Summary: Fungal infections pose an increasing threat to human health, and the limited availability of clinically approved antifungal agents, coupled with the rise of drug resistance, calls for the development of novel and efficient antifungals. This article summarizes the current knowledge of sulfur-related genes and pathways in Aspergillus fumigatus virulence, highlighting their potential as targets for drug development.
Article
Biotechnology & Applied Microbiology
Zhi Li, Fangwang Shen, Lili Song, Shicui Zhang
Summary: NP20 is a novel antifungal peptide that has the ability to kill spores of Aspergillus niger and Aspergillus fumigatus and directly damage their surface, membrane, cytoplasm, organelle, and nucleus. It is active under temperature stress and a wide range of pH. The mechanisms underlying NP20's antifungal activity include binding with and passing through the fungal cell wall, interfering with the lipid membrane, inducing intracellular ROS production, DNA fragmentation, and protein synthesis inhibition of the fungal cells.
MARINE BIOTECHNOLOGY
(2022)
Review
Microbiology
Dilan Andres Pimienta, Freiser Eceomo Cruz Mosquera, Isabella Palacios Velasco, Maria Giraldo Rodas, Jose Onate-Garzon, Yamil Liscano
Summary: The global prevalence of fungal infections, particularly aspergillosis which was previously limited to immunosuppressed individuals, is on the rise. Aspergillus fumigatus, resistant to antimycotics such as fluconazole, poses a public health threat by causing allergic bronchopulmonary aspergillosis. Antifungal peptides, by forming pores in membranes through electrostatic interactions with phospholipids and inducing cell death as well as inhibiting protein synthesis and replication, offer a viable alternative. Engineering these peptides using nanotechnology can enhance efficacy, reduce dosages, and minimize immune responses.
Article
Biochemistry & Molecular Biology
Patrick Feurle, Andreas Abentung, Isabella Cera, Nico Wahl, Cornelia Ablinger, Michael Bucher, Eduard Stefan, Simon Sprenger, David Teis, Andre Fischer, Aodan Laighneach, Laura Whitton, Derek W. Morris, Galina Apostolova, Georg Dechant
Summary: Interactions between SATB2 and the inner nuclear membrane protein LEMD2 influence gene expression programs in pyramidal neurons that are linked to cognitive ability and psychiatric disorder etiology.
Article
Radiology, Nuclear Medicine & Medical Imaging
Marcin Radzik, Justyna Pijarowska-Kruszyna, Antoni Jaron, Michal Maurin, Clemens Decristoforo, Renata Mikolajczak, Piotr Garnuszek
Summary: The study aimed to develop and validate an HPLC method for RCP analysis and identification of metal complexes impurities in radiopharmaceutical preparations of DOTA-chelated peptides. Complexes of DOTA-TATE and DOTA-TOC with several metals were prepared and their molar absorption coefficients at 220nm were determined. The developed method enabled quantitative determination of non-labelled peptide in the radioactive preparation and assessment of the total content of the peptide using the HPLC method with UV detection.
NUCLEAR MEDICINE AND BIOLOGY
(2021)
Article
Medicine, General & Internal
Steffen Bayerschmidt, Christian Uprimny, Alexander Stephan Kroiss, Josef Fritz, Bernhard Nilica, Hanna Svirydenka, Clemens Decristoforo, Elisabeth von Guggenberg, Wolfgang Horninger, Irene Johanna Virgolini
Summary: The study evaluated the diagnostic performance of early static imaging in comparison to 68Ga-PSMA-11 PET imaging conducted 60 min post-injection in prostate cancer patients with biochemical recurrence. The results showed no statistically significant differences between the combination of early and 60 min post-injection imaging, suggesting that additional early static imaging may not be routinely recommended for assessing biochemical recurrence in prostate cancer patients following a protocol with forced diuresis.
Article
Microbiology
Joachim Pfister, Milos Petrik, Katerina Bendova, Barbara Matuszczak, Ulrike Binder, Matthias Misslinger, Alexander Kuehbacher, Fabio Gsaller, Hubertus Haas, Clemens Decristoforo
Summary: Novel antifungal siderophore conjugates with promising fungal growth inhibition and the possibility to perform PET imaging combine both therapeutic and diagnostic potential in a theranostic compound for IPA caused by A. fumigatus.
Article
Microbiology
Matthias Misslinger, Milos Petrik, Joachim Pfister, Isabella Hubmann, Katerina Bendova, Clemens Decristoforo, Hubertus Haas
Summary: Fungal infections pose a serious threat to immunocompromised patients, highlighting the importance of early and reliable diagnosis for treatment. Bacterial-produced siderophore desferrioxamine B (DFO-B) and gallium-68-complexed DFO-B have been used for molecular imaging of bacterial infections by PET, with recent evidence demonstrating potential clinical applications in fungal infections.
Article
Chemistry, Medicinal
Anton A. Hoermann, Maximilian Klingler, Christine Rangger, Christian Mair, Clemens Decristoforo, Christian Uprimny, Irene J. Virgolini, Elisabeth von Guggenberg
Summary: The new minigastrin analog DOTA-MGS5 shows promise for targeting CCK2R-expressing tumors, with extensive preclinical studies supporting its safety and efficacy for potential clinical translation. Using Ga-68-labeled DOTA-MGS5 for PET/CT imaging requires careful consideration of quality and safety aspects, with standardized production and non-clinical safety studies indicating suitability for exploratory clinical trials.
Article
Energy & Fuels
Mario M. Aguiar, Laise C. Wadt, Debora S. Vilar, Maria L. Hernandez-Macedo, Vineet Kumar, Regina Teresa R. Monteiro, Sikandar I. Mulla, Ram Naresh Bharagava, Hafiz M. N. Iqbal, Muhammad Bilal, Luiz Fernando R. Ferreira
Summary: This study successfully produced exopolysaccharides and fungal biomass using different species of Pleurotus genus in vinasse medium. The results showed that 100% vinasse is a suitable medium for increasing protein-rich biomass, exopolysaccharide content, and minerals accumulation. Additionally, treatment of vinasse with Pleurotus fungi efficiently removed color and turbidity. The resulting biomass can be used for animal feed and human food supplementation, adding economic value to vinasse production.
BIOMASS CONVERSION AND BIOREFINERY
(2022)
Article
Cell Biology
Sinead Schwabl, David Teis
Summary: The majority of eukaryotic cells' proteome is targeted to organelles, and distinct protein quality control mechanisms operate on organelles to maintain protein homeostasis. This study focuses on the protein quality control pathways at the Golgi apparatus and discusses the mechanisms for retrieving misfolded and orphaned proteins, extracting proteins for degradation, and selectively targeting proteins to lysosomes.
CURRENT OPINION IN CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anton Amadeus Hoermann, Elisabeth Plhak, Maximilian Klingler, Christine Rangger, Joachim Pfister, Gert Schwach, Herbert Kvaternik, Elisabeth von Guggenberg
Summary: This study presents a new minigastrin analog, DOTA-MGS8, targeting the cholecystokinin-2 receptor (CCK2R). Ga-68-labeled DOTA-MGS8 was successfully synthesized using an automated synthesis module, and preclinical studies demonstrated its high receptor-specific cell internalization and favorable biodistribution profile. This suggests that stabilized MG analogs like DOTA-MGS8 have the potential for high-sensitivity positron emission tomography in patients with CCK2R-related malignancies.
Article
Microbiology
Mario Aguiar, Thomas Orasch, Yana Shadkchan, Patricia Caballero, Joachim Pfister, Luis Enrique Sastre-Velasquez, Fabio Gsaller, Clemens Decristoforo, Nir Osherov, Hubertus Haas
Summary: Siderophores are important for fungal virulence and can be used for in vivo imaging and biomarkers of fungal infections. This study identified a crucial siderophore transporter for virulence and elucidated its potential in translation and evolutionary conservation.
Article
Biochemistry & Molecular Biology
Leonhard Gruber, Clemens Decristoforo, Christian Uprimny, Peter Hohenberger, Stefan O. Schoenberg, Francesca Orlandi, Maurizio Franco Mariani, Claudia Manzl, Maria Theresia Kasseroler, Herbert Tilg, Bettina Zelger, Werner R. Jaschke, Irene J. Virgolini
Summary: This study reports the diagnostic properties and factors influencing the uptake of Ga-68-NeoBOMB1 in advanced gastrointestinal stromal tumor (GIST) patients. The results demonstrate variable tumor uptake in some patients, which is correlated with lesion vitality, suggesting its potential as a therapeutic approach in selected cases.
Article
Medicine, Research & Experimental
Volker Morath, Corinna Brandt, Friedrich-Christian Deuschle, Claudia T. Mendler, Birgit Blechert, Dominik Summer, Cyril Barinka, Clemens Decristoforo, Wolfgang A. Weber, Markus Schwaiger, Arne Skerra
Summary: Anticalin proteins targeting PSMA with tailored plasma half-life using PASylation technology are promising radioligands for PET imaging of xenograft tumors in mice. PET imaging using the FsC radiochelator is superior to Dfo radiochelator and adjusting the plasma half-life of Anticalin radioligands using PASylation technology can increase radioisotope accumulation within the tumor.
MOLECULAR PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Doroteja Novak, Barbara Janota, Anton Amadeus Hoermann, Agnieszka Sawicka, Marko Kroselj, Alicja Hubalewska-Dydejczyk, Melpomeni Fani, Renata Mikolajczak, Petra Kolenc, Clemens Decristoforo, Piotr Garnuszek
Summary: The broad availability and cost-effectiveness of Mo-99/Tc-99m generators worldwide have supported the use and development of novel Tc-99m-labelled radiopharmaceuticals. This study aimed to provide a reliable method for the facile preparation of a Tc-99m-labelled SST2 antagonist, [Tc-99m]Tc-TECANT-1, in a hospital radiopharmacy setting for a multi-centre clinical trial. A freeze-dried three-vial kit was successfully developed to ensure successful and reproducible on-site preparation of the radiopharmaceutical for human use shortly before administration.
Article
Microbiology
Isidor Happacher, Mario Aguiar, Mostafa Alilou, Beate Abt, Tim J. H. Baltussen, Clemens Decristoforo, Willem J. G. Melchers, Hubertus Haas
Summary: Aspergillus fumigatus, a common airborne fungal pathogen, utilizes two high-affinity iron uptake mechanisms, reductive iron assimilation (RIA) and siderophore-mediated iron acquisition (SIA), to maintain iron homeostasis and enhance virulence. This study focused on understanding iron acquisition during germination and revealed that ferricrocin, a siderophore, plays a crucial role in this process. Ferricrocin was found to be secreted and taken up during early germination, regardless of iron availability, indicating developmental regulation of this iron acquisition system. These findings provide insights into the mechanisms of iron acquisition and suggest potential targets for the diagnosis and treatment of fungal infections.
MICROBIOLOGY SPECTRUM
(2023)
Article
Chemistry, Medicinal
Martin Kraihammer, Piotr Garnuszek, Andreas Bauman, Michael Maurin, Manuel Alejandre Lafont, Roland Haubner, Elisabeth von Guggenberg, Michael Gabriel, Clemens Decristoforo
Summary: The study validated a method for quality control of [Lu-177]Lu-PSMA I&T, including determination of radiochemical purity, identity testing and limit test for PSMA I&T by HPLC and TLC. The combination of HPLC and TLC provides a reliable tool for quality control of [Lu-177]Lu-PSMA I&T.
EJNMMI RADIOPHARMACY AND CHEMISTRY
(2023)