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Metallophores in Diagnosing Infectious Diseases
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Metallophores in Diagnosing Infectious Diseases

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Cell Biology, Metabolism and Physiology".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 13350

Special Issue Editor

Dr. Vladimír Havlíček

E-Mail Website
Guest Editor
Institute of Microbiology of the Academy of Sciences of the Czech Republic, Laboratory of Molecular Structure Characterization, Prague, Czech Republic

Special Issue Information

Dear Colleagues,

Metallophores represent microbial pleiotropic virulence factors (contributing to metal hijack, resistance to ROS, and the ability to produce sexual spores); they have a high secretion rate at the invasive stage of a disease, and can be strain-specific. They exert non-canonical roles as they are active in acquiring non-iron metals, modulating host functions, and are used as therapeutics in Trojan-horse antibiotic conjugate strategies or as vaccine components. However, their functions in superinfections for which viruses paved the way remain unclear. Metallophores are promising markers of infectious diseases, and their medical applications have expanded into critical care, dermatology, veterinary medicine, and numerous other related disciplines. This Special Issue aims at under-studied fields of metallophore research, with a focus on the diagnostic contributions including but not limited to:

  1. Metallophore partitions into the bloodstream, breath condensate, urine, and diverse human/animal organs.
  2. Biomarker stability, metal coordination, and pH dependency reflected in metal nutrition or passivation processes.
  3. Metallophores in microbiome biofilm formation and specific roles in host–pathogen interface.
  4. Cellular target definitions for microbial secondary metabolites affecting the host immune response.
  5. Non-infectious links among metallophore secretion and a tumor development.
  6. Metallophore resorption, metabolism, and degradation (metal-containing forms versus demetallated forms).
  7. Biosensors for metallophore, metallophore/binding protein, or microbial enrichment; recoveries from clinical specimens.
  8. Metallophore and metallophore-conjugate imaging.
  9. Other clinical metallophore topics for which we have more questions than answers.

Dr. Vladimír Havlíček
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Fungi is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • metallophore
  • biofilm
  • biosensor
  • clinical
  • critical care
  • degradation
  • enrichment
  • chalcophore
  • metabolism
  • metal nutrition
  • partition
  • passivation
  • recovery
  • resorption
  • siderophore
  • stability
  • zincophore
  • virulence
  • imaging

Published Papers (6 papers)

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13 pages, 5651 KiB  
Article
Diagnosis of Aspergillosis in Horses
by Radim Dobiáš, Petr Jahn, Katarina Tóthová, Olga Dobešová, Denisa Višňovská, Rutuja Patil, Anton Škríba, Pavla Jaworská, Miša Škorič, Libor Podojil, Michaela Kantorová, Jakub Mrázek, Eva Krejčí, David A. Stevens and Vladimír Havlíček
J. Fungi 2023, 9(2), 161; https://doi.org/10.3390/jof9020161 - 25 Jan 2023
Cited by 4 | Viewed by 2347
Abstract
Invasive pulmonary aspergillosis (IPA) may be a rare cause of granulomatous pneumonia in horses. The mortality of IPA is almost 100%; direct diagnostic tools in horses are needed. Bronchoalveolar lavage fluid (BALF) and serum samples were collected from 18 horses, including individuals suffering [...] Read more.
Invasive pulmonary aspergillosis (IPA) may be a rare cause of granulomatous pneumonia in horses. The mortality of IPA is almost 100%; direct diagnostic tools in horses are needed. Bronchoalveolar lavage fluid (BALF) and serum samples were collected from 18 horses, including individuals suffering from IPA (n = 1), equine asthma (EA, n = 12), and 5 healthy controls. Serum samples were collected from another 6 healthy controls. Samples of BALF (n = 18) were analyzed for Aspergillus spp. DNA, fungal galactomannan (GM), ferricrocin (Fc), triacetylfusarinin C (TafC), and gliotoxin (Gtx). Analysis of 24 serum samples for (1,3)-β-D-glucan (BDG) and GM was performed. Median serum BDG levels were 131 pg/mL in controls and 1142 pg/mL in IPA. Similar trends were observed in BALF samples for GM (Area under the Curve (AUC) = 0.941) and DNA (AUC = 0.941). The fungal secondary metabolite Gtx was detected in IPA BALF and lung tissue samples (86 ng/mL and 2.17 ng/mg, AUC = 1). Full article
(This article belongs to the Special Issue Metallophores in Diagnosing Infectious Diseases)
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11 pages, 734 KiB  
Article
Distinguishing Invasive from Chronic Pulmonary Infections: Host Pentraxin 3 and Fungal Siderophores in Bronchoalveolar Lavage Fluids
by Radim Dobiáš, Pavla Jaworská, Valeria Skopelidou, Jan Strakoš, Denisa Višňovská, Marcela Káňová, Anton Škríba, Pavlína Lysková, Tomáš Bartek, Ivana Janíčková, Radovan Kozel, Lucie Cwiková, Zbyněk Vrba, Milan Navrátil, Jan Martinek, Pavla Coufalová, Eva Krejčí, Vít Ulmann, Milan Raška, David A. Stevens and Vladimír Havlíčekadd Show full author list remove Hide full author list
J. Fungi 2022, 8(11), 1194; https://doi.org/10.3390/jof8111194 - 12 Nov 2022
Cited by 6 | Viewed by 2523
Abstract
The multiple forms of pulmonary aspergillosis caused by Aspergillus species are the most common respiratory mycoses. Although invasive, the analysis of diagnostic biomarkers in bronchoalveolar lavage fluid (BALF) is a clinical standard for diagnosing these conditions. The BALF samples from 22 patients with [...] Read more.
The multiple forms of pulmonary aspergillosis caused by Aspergillus species are the most common respiratory mycoses. Although invasive, the analysis of diagnostic biomarkers in bronchoalveolar lavage fluid (BALF) is a clinical standard for diagnosing these conditions. The BALF samples from 22 patients with proven or probable aspergillosis were assayed for human pentraxin 3 (Ptx3), fungal ferricrocin (Fc), and triacetylfusarinine C (TafC) in a retrospective study. The infected group included patients with invasive pulmonary aspergillosis (IPA) and chronic aspergillosis (CPA). The BALF data were compared to a control cohort of 67 patients with invasive pulmonary mucormycosis (IPM), non-Aspergillus colonization, or bacterial infections. The median Ptx3 concentrations in patients with and without aspergillosis were 4545.5 and 242.0 pg/mL, respectively (95% CI, p < 0.05). The optimum Ptx3 cutoff for IPA was 2545 pg/mL, giving a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 100, 98, 95, and 100%, respectively. The median Ptx3 concentration for IPM was high at 4326 pg/mL. Pentraxin 3 assay alone can distinguish IPA from CPA and invasive fungal disease from colonization. Combining Ptx3 and TafC assays enabled the diagnostic discrimination of IPM and IPA, giving a specificity and PPV of 100%. Full article
(This article belongs to the Special Issue Metallophores in Diagnosing Infectious Diseases)
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12 pages, 2549 KiB  
Article
Desferrioxamine B-Mediated Pre-Clinical In Vivo Imaging of Infection by the Mold Fungus Aspergillus fumigatus
by Matthias Misslinger, Milos Petrik, Joachim Pfister, Isabella Hubmann, Katerina Bendova, Clemens Decristoforo and Hubertus Haas
J. Fungi 2021, 7(9), 734; https://doi.org/10.3390/jof7090734 - 08 Sep 2021
Cited by 7 | Viewed by 2066
Abstract
Fungal infections are a serious threat, especially for immunocompromised patients. Early and reliable diagnosis is crucial to treat such infections. The bacterially produced siderophore desferrioxamine B (DFO-B) is utilized by a variety of microorganisms for iron acquisition, while mammalian cells lack the uptake [...] Read more.
Fungal infections are a serious threat, especially for immunocompromised patients. Early and reliable diagnosis is crucial to treat such infections. The bacterially produced siderophore desferrioxamine B (DFO-B) is utilized by a variety of microorganisms for iron acquisition, while mammalian cells lack the uptake of DFO-B chelates. DFO-B is clinically approved for a variety of long-term chelation therapies. Recently, DFO-B-complexed gallium-68 ([68Ga]Ga-DFO-B) was shown to enable molecular imaging of bacterial infections by positron emission tomography (PET). Here, we demonstrate that [68Ga]Ga-DFO-B can also be used for the preclinical molecular imaging of pulmonary infection caused by the fungal pathogen Aspergillus fumigatus in a rat aspergillosis model. Moreover, by combining in vitro uptake studies and the chemical modification of DFO-B, we show that the cellular transport efficacy of ferrioxamine-type siderophores is impacted by the charge of the molecule and, consequently, the environmental pH. The chemical derivatization has potential implications for its diagnostic use and characterizes transport features of ferrioxamine-type siderophores. Full article
(This article belongs to the Special Issue Metallophores in Diagnosing Infectious Diseases)
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9 pages, 1142 KiB  
Article
Freeing Aspergillus fumigatus of Polymycovirus Infection Renders It More Resistant to Competition with Pseudomonas aeruginosa Due to Altered Iron-Acquiring Tactics
by Rutuja H. Patil, Ioly Kotta-Loizou, Andrea Palyzová, Tomáš Pluháček, Robert H. A. Coutts, David A. Stevens and Vladimír Havlíček
J. Fungi 2021, 7(7), 497; https://doi.org/10.3390/jof7070497 - 22 Jun 2021
Cited by 12 | Viewed by 2009 | Correction
Abstract
A virus-free (VF) A. fumigatus isolate has been shown to be resistant in competition with Pseudomonas as compared to the isogenic line infected with Aspergillus fumigatus polymycovirus 1 (AfuPmV-1), and this phenotype was apparently related to alterations in iron metabolism. Here we investigated [...] Read more.
A virus-free (VF) A. fumigatus isolate has been shown to be resistant in competition with Pseudomonas as compared to the isogenic line infected with Aspergillus fumigatus polymycovirus 1 (AfuPmV-1), and this phenotype was apparently related to alterations in iron metabolism. Here we investigated further the mechanisms underpinning this phenotype. The extracellular siderophore profiles of five isogenic VF and virus-infected (VI) strains were sampled at 24, 31, 48, 54, and 72 h in submerged cultures and quantitatively examined by liquid chromatography and mass spectrometry. Intracellular profiles of conidia and cultures at the stationary growth phase were defined. VF A. fumigatus demonstrated the best fitness represented by the fastest onset of its exponential growth when grown on an iron-limited mineral medium. The exponential phase and transitional production phase of the extracellular triacetylfusarinine C (TafC) were achieved at 24 and 31 h, respectively, contrary to VI strains, which acted more slowly. As a result, the TafC reservoir was consumed sooner in the VF strain. Additionally, the VF strain had lower ferricrocin and higher hydroxyferricrocin content in the pellet during the stationary phase. All of these differences were significant (Kruskal–Wallis, p < 0.01). In our study, the siderophore reservoir of a VF strain was consumed sooner, improving the fitness of the VF strain in competition with P. aeruginosa. Full article
(This article belongs to the Special Issue Metallophores in Diagnosing Infectious Diseases)
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3 pages, 1084 KiB  
Correction
Correction: Patil et al. Freeing Aspergillus fumigatus of Polymycovirus Infection Renders It More Resistant to Competition with Pseudomonas aeruginosa Due to Altered Iron-Acquiring Tactics. J. Fungi 2021, 7, 497
by Rutuja H. Patil, Ioly Kotta-Loizou, Andrea Palyzová, Tomáš Pluháček, Robert H. A. Coutts, David A. Stevens and Vladimír Havlíček
J. Fungi 2022, 8(7), 691; https://doi.org/10.3390/jof8070691 - 29 Jun 2022
Viewed by 1033
Abstract
In the original publication [...] Full article
(This article belongs to the Special Issue Metallophores in Diagnosing Infectious Diseases)
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13 pages, 1834 KiB  
Case Report
Noninvasive Combined Diagnosis and Monitoring of Aspergillus and Pseudomonas Infections: Proof of Concept
by Radim Dobiáš, Anton Škríba, Tomáš Pluháček, Miloš Petřík, Andrea Palyzová, Marcela Káňová, Eva Čubová, Jiří Houšť, Jiří Novák, David A. Stevens, Goran Mitulovič, Eva Krejčí, Petr Hubáček and Vladimír Havlíček
J. Fungi 2021, 7(9), 730; https://doi.org/10.3390/jof7090730 - 06 Sep 2021
Cited by 11 | Viewed by 2437
Abstract
In acutely ill patients, particularly in intensive care units or in mixed infections, time to a microbe-specific diagnosis is critical to a successful outcome of therapy. We report the application of evolving technologies involving mass spectrometry to diagnose and monitor a patient’s course. [...] Read more.
In acutely ill patients, particularly in intensive care units or in mixed infections, time to a microbe-specific diagnosis is critical to a successful outcome of therapy. We report the application of evolving technologies involving mass spectrometry to diagnose and monitor a patient’s course. As proof of this concept, we studied five patients and used two rat models of mono-infection and coinfection. We report the noninvasive combined monitoring of Aspergillus fumigatus and Pseudomonas aeruginosa infection. The invasive coinfection was detected by monitoring the fungal triacetylfusarinine C and ferricrocin siderophore levels and the bacterial metabolites pyoverdin E, pyochelin, and 2-heptyl-4-quinolone, studied in the urine, endotracheal aspirate, or breath condensate. The coinfection was monitored by mass spectrometry followed by isotopic data filtering. In the rat infection model, detection indicated 100-fold more siderophores in urine compared to sera, indicating the diagnostic potential of urine sampling. The tools utilized in our studies can now be examined in large clinical series, where we could expect the accuracy and speed of diagnosis to be competitive with conventional methods and provide advantages in unraveling the complexities of mixed infections. Full article
(This article belongs to the Special Issue Metallophores in Diagnosing Infectious Diseases)
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