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.
PURPOSE OF REVIEW: RTX toxin action often defines the outcome of bacterial infections. Here, we discuss the progress in understanding the impacts of RTX toxin activities on host immunity. RECENT FINDINGS: Bordetella pertussis CyaA activity paralyzes sentinel phagocytic cells by elevating cellular cAMP levels and blocks differentiation of infiltrating monocytes into bactericidal macrophages, promoting also de-differentiation of resident alveolar macrophages into monocyte-like cells. Vibrio cholerae multifunctional autoprocessing repeats-in-toxins (MARTX), through Rho inactivating and α/β-hydrolase (ABH) domain action blocks mitogen-activated protein kinase signaling in epithelial cells and dampens the inflammatory responses of intestinal epithelia by blocking immune cell recruitment. The action of actin crosslinking effector domain and Ras/Rap1-specific endopeptidase (RRSP) domains of MARTX compromises the phagocytic ability of macrophages. Aggregatibacter actinomycetemcomitans LtxA action triggers neutrophil elastase release into periodontal tissue, compromising the epithelial barrier and promoting bacterial spreads into deeper tissue. SUMMARY: Action of RTX toxins enables bacterial pathogens to cope with the fierce host immune defenses. RTX toxins often block phagocytosis and bactericidal reactive oxygen species and NO production. Some RTX toxins can reprogram the macrophages to less bactericidal cell types. Autophagy is hijacked for example by the activity of the V. cholerae ABH effector domain of the MARTX protein. Subversion of immune functions by RTX toxins thus promotes bacterial survival and proliferation in the host.
- MeSH
- adaptivní imunita MeSH
- Bacteria metabolismus patogenita MeSH
- bakteriální toxiny toxicita MeSH
- buňky NK účinky léků MeSH
- dendritické buňky účinky léků MeSH
- epitelové buňky účinky léků MeSH
- lidé MeSH
- makrofágy účinky léků MeSH
- monocyty účinky léků MeSH
- virulence MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- antibakteriální látky terapeutické užití MeSH
- Borrelia burgdorferi izolace a purifikace klasifikace MeSH
- lidé MeSH
- lymeská nemoc epidemiologie farmakoterapie patofyziologie MeSH
- Check Tag
- lidé MeSH
- Geografické názvy
- Evropa MeSH
