PURPOSE OF REVIEW: Invasive fungal diseases (IFDs) such as invasive aspergillosis continue to be associated with high morbidity and mortality while presenting significant diagnostic challenges. Siderophores are high-affinity Fe 3+ chelators produced by Aspergillus spp. and other fungi capable of causing IFD. Previously evaluated as a treatment target in mucormycosis, siderophores have recently emerged as new diagnostic targets for invasive aspergillosis and scedosporiosis. Here, we review the diagnostic potential of siderophores for diagnosing IFD, with a particular focus on invasive aspergillosis. RECENT FINDINGS: The major secreted siderophore of A. fumigatus , triacetylfusarinine C (TAFC), has been successfully detected by mass spectrometry in serum, BALF and urine of patients with invasive aspergillosis, with promising sensitivities and specificities in single-centre studies. Intracellular uptake of siderophores has also been utilized for imaging, wherein fungal siderophores have been conjugated with the easy-to-produce radioactive isotope gallium-68 ( 68 Ga) to visualize infected body sites in PET. For the Scedosporium apiospermum complex, another siderophore N(α)-methyl coprogen B has been shown promising as a marker for airway colonization in early studies. SUMMARY: Siderophores and particular TAFC have the potential to revolutionize diagnostic pathways for invasive aspergillosis and other mould infections. However, larger multicentre studies are needed to confirm these promising performances. Methods that allow rapid and cost-effective measurements in routine clinical practice need to be developed, particularly when TAFC is used as a biomarker in patient specimens.
Siderophores represent important microbial virulence factors and infection biomarkers. Their monitoring in fermentation broths, bodily fluids, and tissues should be reproducible. Similar isolation, characterization, and quantitation studies can often have conflicting results, and without proper documentation of sample collection, data processing, and analysis methods, it is difficult to reexamine the data and reconcile these differences. In this Springer Nature Protocol, we present the procedure optimized for ferricrocin/triacetylfusarinine C extraction from biological material as well as for tissue fixation and cryosectioning for optical microscopy and for both elemental and molecular mass spectrometry imaging. Special attention is paid to siderophore data mining from conventional and product ion mass spectra, liquid chromatography, and mass spectrometry imaging datasets, performed here by our free software called CycloBranch.
- MeSH
- Aspergillus fumigatus metabolismus MeSH
- biologické markery analýza MeSH
- chromatografie kapalinová metody MeSH
- data mining metody MeSH
- datové soubory jako téma MeSH
- ferrichrom analogy a deriváty izolace a purifikace metabolismus MeSH
- fixace tkání metody MeSH
- hmotnostní spektrometrie metody MeSH
- invazivní plicní aspergilóza diagnóza mikrobiologie MeSH
- kryoultramikrotomie metody MeSH
- krysa rodu rattus MeSH
- kyseliny hydroxamové izolace a purifikace metabolismus MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- siderofory izolace a purifikace metabolismus MeSH
- software MeSH
- železité sloučeniny izolace a purifikace metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Certain non-steroidal anti-inflammatory drugs can inhibit fungal growth, fungal prostaglandin E2 production, and enzyme activation. This study aims to investigate the antifungal effect of nimesulide against pathogenic filamentous fungi and yeast. The experiments detailed below were also designed to investigate whether the action is dependent on E2 fungal prostaglandins. Our data showed that nimesulide exhibited potent antifungal activity, mainly against Trichophyton mentagrophytes (ATCC 9533) and Cryptococcus neoformans with MIC values of 2 and 62 μg/mL, respectively. This drug was also able to inhibit the growth of clinic isolates of filamentous fungi, such as Aspergillus fumigatus, and dermatophytes, such as T. rubrum, T. mentagrophytes, Epidermophyton floccosum, Microsporum canis, and M. gypseum, with MIC values ranging from 112 to 770 μg/mL. Our data also showed that the inhibition of fungal growth by nimesulide was mediated by a mechanism dependent on PGE2, which led to the inhibition of essential fungal enzymes. Thus, we concluded that nimesulide exerts a fungicidal effect against pathogenic filamentous fungi and yeast, involving the inhibition of fungal prostaglandins and fungal enzymes important to the fungal growth and colonization.
- MeSH
- antifungální látky farmakologie MeSH
- Arthrodermataceae účinky léků růst a vývoj metabolismus MeSH
- Aspergillus fumigatus účinky léků růst a vývoj metabolismus MeSH
- Cryptococcus neoformans účinky léků růst a vývoj metabolismus MeSH
- dinoproston antagonisté a inhibitory biosyntéza MeSH
- mikrobiální testy citlivosti MeSH
- sulfonamidy farmakologie MeSH
- Trichophyton účinky léků růst a vývoj metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
Aspergillus fumigatus je oportunně patogenní vláknitá houba, která je schopna vytvářet biofilm, a tím způsobovat velice závažné až fatální onemocnění u imunosuprimovaných pacientů (plicní aspergilom, aspergilovou bronchitidu, alergickou bronchopulmonální aspergilózu, infekci biomateriálů a mnoho dalších). Proto je nezbytné studovat podrobně mechanismy tvorby těchto vláknitých biofilmů, pochopit molekulární mechanismy vedoucí ke vzniku jejich rezistence a případně navrhnout nové látky, které by pomohly předcházet úmrtí zasažených pacientů.
Aspergillus fumigatus is an opportunistic pathogenic filamentous fungus which is capable forming a biofilm. The biofilm of A. fumigatus couses very serious or even fatal diseases of immunosuppressed patients (pulmonary aspergilloma, Aspergillus bronchitis, allergic bronchopulmonary aspergillosis, infection of biomaterials and many others). Therefore it is necessary to study the mechanisms of biofilm forming by this filamentous fungus, understand the molecular mechanisms of biofilm resistance and propose new substances for treating these infections.
- MeSH
- Aspergillus fumigatus * fyziologie metabolismus účinky léků MeSH
- aspergilóza * farmakoterapie klasifikace komplikace MeSH
- biofilmy * účinky léků MeSH
- fungální léková rezistence MeSH
- lidé MeSH
- plicní aspergilóza etiologie farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Inflammatory or anti-inflammatory? That is the question as far as the acute-phase response and its mediators, the pentraxins, are concerned. Only some ten years ago, the classical or short pentraxin C-reactive protein and the newly discovered long pentraxin PTX3 were considered to exert most of the detrimental effects of acute inflammation, whether microbial or sterile in origin. However, accumulating evidence suggests an at least dichotomous, context-dependent outcome attributable to the pentraxins, if not a straightforward anti-inflammatory nature of the acute-phase response. This paper is focused on the inherent effects of pentraxin 3 in inflammatory responses, mainly in coronary artery disease and in Aspergillus fumigatus infection. Both are examples of inflammatory reactions in which PTX3 is substantially involved; the former sterile, the latter infectious in origin. Apart from different inducing noxae, similarities in the pathogenesis of the two are striking. All the same, the introductory question still persists: is the ultimate impact of PTX3 in these conditions inflammatory or anti-inflammatory, paradoxical as the latter might appear? We try to provide an answer such as it emerges in the light of recent findings.
- MeSH
- Aspergillus fumigatus metabolismus MeSH
- ateroskleróza metabolismus MeSH
- C-reaktivní protein genetika fyziologie MeSH
- infarkt myokardu metabolismus MeSH
- kardiovaskulární nemoci krev metabolismus MeSH
- komplement MeSH
- lidé MeSH
- myši MeSH
- neutrofily metabolismus MeSH
- přirozená imunita MeSH
- reperfuzní poškození MeSH
- sérový amyloidový protein genetika fyziologie MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
