- Use of isavuconazole in a patient with voriconazole-induced QTc prolongation. [Case Reports]
- TITranspl Infect Dis 2017 Apr 23
- A 22-year-old woman with cystic fibrosis developed QTc-interval prolongation following lung transplantation in the setting of voriconazole therapy. After the discontinuation of voriconazole and initi...
A 22-year-old woman with cystic fibrosis developed QTc-interval prolongation following lung transplantation in the setting of voriconazole therapy. After the discontinuation of voriconazole and initiation of isavuconazole, her QTc interval normalized. This case highlights the unique property of QTc interval shortening by isavuconazole among the triazole antifungals. This article is protected by copyright. All rights reserved.
- Carbonic anhydrase XII functions in health and disease. [Review]
- GENEGene 2017 Apr 19
- Human CAXII was initially identified as a cancer marker in different cancers and tumors. Expression of CAXII is regulated by hypoxia and estrogen receptors. CAXII expression has been also detected in...
Human CAXII was initially identified as a cancer marker in different cancers and tumors. Expression of CAXII is regulated by hypoxia and estrogen receptors. CAXII expression has been also detected in several tissues, whereas in cancer and tumor tissues its expression is several fold higher. In brain tumors, an alternatively spliced form of CAXII is expressed. Higher expression of CAXII in breast cancer is indicative of lower grade disease. CAXII plays a key role in several physiological functions. Mutation in the CAXII gene causes cystic fibrosis-like syndrome and salt wasting disease. CAXII is also seen in nuclear pulposus cells of the vertebrae. Aging dependent stiffness or degeneration of backbone correlates with CAXII expression level. This finding suggests a possible implication of CAXII as a biomarker for chronic back pain and a pharmacological target for possible treatment of chronic back pain.
- Orkambi in patients with severe disease - Bumps in the road to CFTR modulation. [Editorial]
- JCJ Cyst Fibros 2017 Apr 19
- Renal findings in patients with Mulibrey nanism. [Journal Article]
- PNPediatr Nephrol 2017 Apr 22
- CONCLUSIONS: Genetic defects in the TRIM37 gene lead to an increased risk for kidney anomalies, renal tumors, and solitary cysts in addition to glomerular cystic lesions, but not to progressive deterioration of renal function.
- The Use of Synthetic Hybrid Strains to Determine the Role of Replicon 3 in Virulence of the Burkholderia cepacia Complex. [Journal Article]
- AEAppl Environ Microbiol 2017 Apr 21
- The Burkholderia cepacia complex (Bcc) displays a wealth of metabolic diversity with great biotechnological potential, but the utilisation of these bacteria is limited by their opportunistic pathogen...
The Burkholderia cepacia complex (Bcc) displays a wealth of metabolic diversity with great biotechnological potential, but the utilisation of these bacteria is limited by their opportunistic pathogenicity to humans. The third replicon of the Bcc, megaplasmid pC3 (0.5 to 1.4 Mb, previously chromosome 3), is important for various phenotypes, including virulence, antifungal and proteolytic activities, and the utilization of certain substrates. Approximately half of plasmid pC3 is well-conserved throughout sequenced Bcc members, while the other half is not. To better locate the regions responsible for the key phenotypes, pC3 mutant derivatives of B. cenocepacia H111 carrying large deletions (up to 0.58 Mb) were constructed with the aid of the FLP-FRT recombination system from Saccharomyces cerevisiae The conserved region was shown to confer near full virulence in both a Caenorhabditis elegans and a Galleria mellonella infection model. Antifungal activity was unexpectedly independent of the part of pC3 bearing a previously identified antifungal gene cluster, while proteolytic activity was dependent on the non-conserved part of pC3, which encodes the ZmpA protease. To investigate to what degree pC3-encoded functions are dependent on chromosomally-encoded functions, we transferred pC3 from Burkholderia cenocepacia K56-2 and Burkholderia lata 383 into other pC3-cured Bcc members. We found that although pC3 is highly important for virulence, it was the genetic background of the recipient that determined the pathogenicity level of the hybrid strain. Furthermore, we found that important phenotypes such as antifungal activity, proteolytic activity and some substrate utilisation capabilities can be transferred between Bcc members using pC3.Importance The Burkholderia cepacia complex (Bcc) is a group of closely-related bacteria with great biotechnological potential. Some strains produce potent antifungal compounds, can promote plant growth or degrade environmental pollutants. However, their agricultural potential is limited by their opportunistic pathogenicity, particularly for cystic fibrosis patients. Despite much study their virulence remains poorly understood. The third replicon, pC3, which is present in all Bcc isolates and is important for pathogenicity, stress resistance and production of antifungal compounds, has recently been reclassified from chromosome to megaplasmid. In this study we identified regions on pC3 important for virulence and antifungal activity, and investigated the role of the chromosomal background for the function of pC3 by exchanging the megaplasmid between different Bcc members. Our results may open a new avenue for the construction of antifungal but non-pathogenic Burkholderia hybrids. Such strains may have great potential as biocontrol strains for protecting fungal-borne diseases of plant crops.
- Co-colonisation with Aspergillus fumigatus and Pseudomonas aeruginosa is associated with poorer health in cystic fibrosis patients: an Irish registry analysis. [Journal Article]
- BPBMC Pulm Med 2017 Apr 21; 17(1):70
- CONCLUSIONS: CF patients co-colonised with AF and PA had poor clinical outcomes comparable to patients persistently colonised with PA, emphasising the clinical significance of co-colonisation with these microorganisms.
- Comparative genomics of Burkholderia multivorans, a ubiquitous pathogen with a highly conserved genomic structure. [Journal Article]
- PlosPLoS One 2017; 12(4):e0176191
- The natural environment serves as a reservoir of opportunistic pathogens. A well-established method for studying the epidemiology of such opportunists is multilocus sequence typing, which in many cas...
The natural environment serves as a reservoir of opportunistic pathogens. A well-established method for studying the epidemiology of such opportunists is multilocus sequence typing, which in many cases has defined strains predisposed to causing infection. Burkholderia multivorans is an important pathogen in people with cystic fibrosis (CF) and its epidemiology suggests that strains are acquired from non-human sources such as the natural environment. This raises the central question of whether the isolation source (CF or environment) or the multilocus sequence type (ST) of B. multivorans better predicts their genomic content and functionality. We identified four pairs of B. multivorans isolates, representing distinct STs and consisting of one CF and one environmental isolate each. All genomes were sequenced using the PacBio SMRT sequencing technology, which resulted in eight high-quality B. multivorans genome assemblies. The present study demonstrated that the genomic structure of the examined B. multivorans STs is highly conserved and that the B. multivorans genomic lineages are defined by their ST. Orthologous protein families were not uniformly distributed among chromosomes, with core orthologs being enriched on the primary chromosome and ST-specific orthologs being enriched on the second and third chromosome. The ST-specific orthologs were enriched in genes involved in defense mechanisms and secondary metabolism, corroborating the strain-specificity of these virulence characteristics. Finally, the same B. multivorans genomic lineages occur in both CF and environmental samples and on different continents, demonstrating their ubiquity and evolutionary persistence.
- Understanding the Entanglement: Neutrophil Extracellular Traps (NETs) in Cystic Fibrosis. [Review]
- FCFront Cell Infect Microbiol 2017; 7:104
- Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the gene that codes for the CF trans-membrane conductance regulator. These mutations result in abnormal secretions visco...
Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the gene that codes for the CF trans-membrane conductance regulator. These mutations result in abnormal secretions viscous airways of the lungs, favoring pulmonary infection and inflammation in the middle of neutrophil recruitment. Recently it was described that neutrophils can contribute with disease pathology by extruding large amounts of nuclear material through a mechanism of cell death known as Neutrophil Extracellular Traps (NETs) into the airways of patients with CF. Additionally, NETs production can contribute to airway colonization with bacteria, since they are the microorganisms most frequently found in these patients. In this review, we will discuss the implication of individual or mixed bacterial infections that most often colonize the lung of patients with CF, and the NETs role on the disease.
- CFTR-dependent defect in alternatively-activated macrophages in cystic fibrosis. [Journal Article]
- JCJ Cyst Fibros 2017 Apr 17
- CONCLUSIONS: CFTR-dependent imbalance of macrophage phenotypes and functions could contribute to the exaggerated inflammatory response seen in CF lung disease.
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- Curcumin/poly(2-methyl-2-oxazoline-b-tetrahydrofuran-b-2-methyl-2-oxazoline) formulation: An improved penetration and biological effect of curcumin in F508del-CFTR cell lines. [Journal Article]
- EJEur J Pharm Biopharm 2017 Apr 17
- Neutral amphiphilic triblock ABA copolymers are of great interest to solubilize hydrophobic drugs. We reported that a triblock ABA copolymer consisting of methyl-2-oxazoline (MeOx) and tetrahydrofura...
Neutral amphiphilic triblock ABA copolymers are of great interest to solubilize hydrophobic drugs. We reported that a triblock ABA copolymer consisting of methyl-2-oxazoline (MeOx) and tetrahydrofuran (THF) (MeOx6-THF19-MeOx6) (TBCP2) can solubilize curcumin (Cur) a very hydrophobic molecule exhibiting multiple therapeutic effects but whose insolubility and low stability in water is a major drawback for clinical applications. Here, we provide evidences by flow cytometry and confocal microscopy that Cur penetration in normal and ΔF508-CFTR human airway epithelial cell lines is facilitated by TBCP2. When used on ΔF508-CFTR cell lines, the Cur/TBCP2 formulation promotes the restoration of the expression of the CFTR protein in the plasma membrane. Furthermore, patch-clamp and MQAE fluorescence experiments show that this effect is associated with a correction of a Cl(-) selective current at the membrane surface of F508del-CFTR cells. The results show the great potential of the neutral amphiphilic triblock copolymer MeOx6-THF19-MeOx6 as carrier for curcumin in a Cystic Fibrosis context. We anticipate that other MeOxn-THFm-MeOxn copolymers could have similar behaviours for other highly insoluble therapeutic drugs or cosmetic active ingredients.