Characteristics of pathogenic fungi and antifungal therapy in cystic fibrosis

2010 ◽  
Vol 8 (8) ◽  
pp. 957-964 ◽  
Author(s):  
Frank-Michael C Müller ◽  
Marc Seidler
Keyword(s):  
Cystic Fibrosis ◽  
Antifungal Therapy ◽  
Pathogenic Fungi

The Regulatory Function of the Molecular Chaperone Hsp90 in the Cell Wall Integrity of Pathogenic Fungi

2018 ◽  
Vol 16 (1) ◽  
pp. 44-53
Author(s):  
Marina Campos Rocha ◽  
Camilla Alves Santos ◽  
Iran Malavazi
Keyword(s):  
Cell Wall ◽  
Antifungal Therapy ◽  
Molecular Chaperone ◽  
Regulatory Protein ◽  
Pathogenic Fungi ◽  
Antifungal Drugs ◽  
Cell Wall Integrity ◽  
Regulatory Function ◽  
Loss Of Function ◽  
Hsp90 Inhibition

Different signaling cascades including the Cell Wall Integrity (CWI), the High Osmolarity Glycerol (HOG) and the Ca2+/calcineurin pathways control the cell wall biosynthesis and remodeling in fungi. Pathogenic fungi, such as Aspergillus fumigatus and Candida albicans, greatly rely on these signaling circuits to cope with different sources of stress, including the cell wall stress evoked by antifungal drugs and the host’s response during infection. Hsp90 has been proposed as an important regulatory protein and an attractive target for antifungal therapy since it stabilizes major effector proteins that act in the CWI, HOG and Ca2+/calcineurin pathways. Data from the human pathogen C. albicans have provided solid evidence that loss-of-function of Hsp90 impairs the evolution of resistance to azoles and echinocandin drugs. In A. fumigatus, Hsp90 is also required for cell wall integrity maintenance, reinforcing a coordinated function of the CWI pathway and this essential molecular chaperone. In this review, we focus on the current information about how Hsp90 impacts the aforementioned signaling pathways and consequently the homeostasis and maintenance of the cell wall, highlighting this cellular event as a key mechanism underlying antifungal therapy based on Hsp90 inhibition.

scholarly journals Use of Nebulized Amphotericin B in the Treatment of Allergic Bronchopulmonary Aspergillosis in Cystic Fibrosis

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
M. Proesmans ◽  
F. Vermeulen ◽  
M. Vreys ◽  
K. De Boeck
Keyword(s):  
Cystic Fibrosis ◽  
Amphotericin B ◽  
Antifungal Therapy ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Lung Infection ◽  
Steroid Withdrawal ◽  
Successful Therapy ◽  
Lipid Complex ◽  
Safety And Efficacy ◽  
Systemic Corticosteroids

Background. Systemic steroids and adjunctive antifungal therapy are the cornerstone in treating allergic bronchopulmonary aspergillosis (ABPA) in the context of CF.Aim. Evaluate the use of inhaled amphotericin B (iAMB) as antifungal agent in this context.Methods. Report of 7 CF patients with recurrent or difficult to treat ABPA and failure to taper systemic corticosteroids treated with AMB deoxycholate (AMB-d) (Fungizone 25 mg 3× a week) or AMB lipid complex (ABLC) (Abelcet 50 mg twice weekly). Successful therapy was defined as steroid withdrawal without ABPA relapse within 12 months.Results. Therapy was successful in 6 of 7 patients treated with iAMB. In 5/6, lung function improved. The patient with treatment failure has concomitant MAC lung infection.Conclusion. Inhaled AMB may be an alternative to commonly used adjunctive antifungal therapy in the treatment of ABPA. More data are needed on safety and efficacy.

Combination antifungal therapy for Scedosporium species in cystic fibrosis

2020 ◽  
Vol 55 (8) ◽  
pp. 1993-1995
Author(s):  
Siân Bentley ◽  
Jane C. Davies ◽  
Siobhán B. Carr ◽  
Ian M. Balfour‐Lynn
Keyword(s):  
Cystic Fibrosis ◽  
Antifungal Therapy ◽  
Scedosporium Species

scholarly journals Combined antifungal therapy is superior to monotherapy in pulmonary scedosporiosis in cystic fibrosis

2019 ◽  
Vol 18 (2) ◽  
pp. 227-232 ◽  
Author(s):  
Carsten Schwarz ◽  
Claudia Brandt ◽  
Volker Melichar ◽  
Christoph Runge ◽  
Eberhard Heuer ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Antifungal Therapy

scholarly journals Aspergillus fumigatusIn-Host HOG pathway mutation for Cystic Fibrosis Lung Microenvironment Persistence

2021 ◽  
Author(s):  
Brandon S. Ross ◽  
Lotus A. Lofgren ◽  
Alix Ashare ◽  
Jason E. Stajich ◽  
Robert A. Cramer
Keyword(s):  
Cystic Fibrosis ◽  
Aspergillus Fumigatus ◽  
Antifungal Therapy ◽  
Clinical Management ◽  
Atmospheric Oxygen ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Clinical Manifestations ◽  
Low Oxygen ◽  
Hog Pathway ◽  
Unique Allele

AbstractThe prevalence ofAspergillus fumigatuscolonization in individuals with Cystic Fibrosis (CF) and subsequent fungal persistence in the lung is increasingly recognized. However, there is no consensus for clinical management ofA. fumigatusin CF individuals, due largely to uncertainty surroundingA. fumigatusCF pathogenesis and virulence mechanisms. To address this gap in knowledge, a longitudinal series ofA. fumigatusisolates from an individual with CF were collected over 4.5 years. Isolate genotypes were defined with whole genome sequencing that revealed both transitory and persistentA. fumigatusin the lung. Persistent lineage isolates grew most readily in a low oxygen culture environment and conidia were more sensitive to oxidative stress inducing conditions compared to non-persistent isolates. Closely related persistent isolates harbor a unique allele of the high osmolarity glycerol (HOG) pathway mitogen activated protein kinase kinase, Pbs2 (pbs2C2). Data suggest this novelpbs2C2allele arosein vivoand is necessary for the fungal response to osmotic stress in a low oxygen environment through hyperactivation of the HOG (SakA) signaling pathway. Hyperactivation of the HOG pathway throughpbs2C2comes at the cost of decreased conidia stress resistance in the presence of atmospheric oxygen levels. These novel findings shed light on pathoadaptive mechanisms ofA. fumigatusin CF, lay the foundation for identifying persistentA. fumigatusisolates that may require antifungal therapy, and highlight considerations for successful culture of persistent fungal CF isolates.ImportanceAspergillus fumigatusinfection causes a spectrum of clinical manifestations. For individuals with Cystic Fibrosis (CF), Allergic Bronchopulmonary Aspergillosis (ABPA) is an established complication, but there is a growing appreciation forA. fumigatusairway persistence in CF disease progression. There currently is little consensus for clinical management ofA. fumigatuslong-term culture positivity in CF. A better understanding ofA. fumigatuspathogenesis mechanisms in CF is expected to yield insights into when antifungal therapies are warranted. Here, a 4.5-year longitudinal collection ofA. fumigatusisolates identified a persistent lineage that harbors a unique allele of the Pbs2 MAPKK necessary for unique CF-relevant stress phenotypes. Importantly forA. fumigatusCF patient diagnostics, this allele provides increased CF lung fitness at a cost of reducedin vitrogrowth in standard laboratory conditions. These data illustrate a molecular mechanism forA. fumigatusCF lung persistence with implications for diagnostics and antifungal therapy.

scholarly journals IPD1.10 Antifungal therapy in adults with cystic fibrosis: experience over ten years

2017 ◽  
Vol 16 ◽  
pp. S57-S58
Author(s):  
S.J. Poole ◽  
W.G. Flight
Keyword(s):  
Cystic Fibrosis ◽  
Antifungal Therapy

Pregnancy in cystic fibrosis of the pancreas

JAMA ◽  
1966 ◽  
Vol 195 (12) ◽  
pp. 993-1000 ◽  
Author(s):  
R. J. Grand
Keyword(s):  
Cystic Fibrosis

Freeze-Fracture Examination of Tight Junctions of Human Eccrine Sweat Glands

1980 ◽  
Vol 38 ◽  
pp. 634-635
Author(s):  
J. V. Briggman ◽  
J. Bigelow ◽  
H. Bank ◽  
S. S. Spicer
Keyword(s):  
Cystic Fibrosis ◽  
Freeze Fracture ◽  
Sweat Glands ◽  
Hypertonic Solution ◽  
Dark Cells ◽  
Clear Cells ◽  
Junctional Complexes ◽  
Secretory Coil ◽  
Eccrine Sweat Glands ◽  
Eccrine Sweat

The prevalence of strands shown by freeze-fracture in the zonula occludens of junctional complexes is thought to correspond closely with the transepi-thelial electrical resistance and with the tightness of the junction and its obstruction to paracellular flow.1 The complexity of the network of junc¬tional complex strands does not appear invariably related to the degree of tightness of the junction, however, as rabbit ileal junctions have a complex network of strands and are permeable to lanthanum. In human eccrine sweat glands the extent of paracellular relative to transcellular flow remains unknown, both for secretion of the isotonic precursor fluid by the coil and for resorption of a hypertonic solution by the duct. The studies reported here undertook, therefore, to determine with the freeze-fracture technique the complexity of the network of ridges in the junctional complexes between cells in the secretory coil and the sweat ducts. Glands from a patient with cystic fibrosis were also examined because an alteration in junctional strands could underlie the decreased Na+ resorption by sweat ducts in this disease. Freeze-fracture replicas were prepared by standard procedures on isolated coil and duct segments of human sweat glands. Junctional complexes between clear cells, between dark cells and between clear and dark cells on the main lumen, and between clear cells on intercellular canaliculi of the coil con¬tained abundant anastomosing closely spaced strands averaging 6.4 + 0.7 (mean + SE) and 9.0 +0.5 (Fig. 1) per complex, respectively. Thus, the junctions in the intercellular canaliculi of the coil appeared comparable in complexity to those of tight epithlia. Occasional junctions exhibited, in addition, 2 to 5 widely spaced anastomosing strands in a very close network basal to the compact network. The fewer junctional complexes observed thus far between the superficial duct cells consisted on the average of 6 strands arranged in a close network and 1 to 4 underlying strands that lay widely separated from one another (Fig. 2). The duct epitelium would, thus, be judged slightly more "leaky" than the coil. Infrequent junctional complexes observed to date in the secretory coil segment of a cystic fibrosis specimen disclosed rela¬tively few closely crowded strands.

Chronic airway colonization by Penicillium emersonii in a patient with cystic fibrosis

1999 ◽  
Vol 37 (4) ◽  
pp. 291-293 ◽  
Author(s):  
B. Cimon ◽  
J. Carrere ◽  
J. P. Chazalette ◽  
J. F. Vinatier ◽  
D. Chabasse ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Airway Colonization ◽  
Chronic Airway

Heat stable toxin of E. coli (STa) stimulates duodenal mucosal bicarbonate secretion in cystic fibrosis knockout mice

2001 ◽  
Vol 120 (5) ◽  
pp. A137-A137
Author(s):  
D CHILDS ◽  
D CROMBIE ◽  
V PRATHA ◽  
Z SELLERS ◽  
D HOGAN ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Knockout Mice ◽  
Bicarbonate Secretion ◽  
E Coli ◽  
Heat Stable
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