Recreation of in-host acquired single nucleotide polymorphisms by CRISPR-Cas9 reveals an uncharacterised gene playing a role in Aspergillus fumigatus azole resistance via a non-cyp51A mediated resistance mechanism.

Recreation of in-host acquired single nucleotide polymorphisms by CRISPR-Cas9 reveals an uncharacterised gene playing a role in Aspergillus fumigatus azole resistance via a non-cyp51A mediated resistance mechanism. Fungal Genet Biol. 2019 May 22;: Authors: Ballard E, Weber J, Melchers WJG, Tammireddy S, Whitfield PD, Brakhage AA, Brown AJP, Verweij PE, Warris A Abstract The human host comprises a range of specific niche environments. In order to successfully persist, pathogens such as Aspergillus fumigatus must adapt to these environments. One key example of in-host adaptation is the development of resistance to azole antifungals. Azole resistance in A. fumigatus is increasingly reported worldwide and the most commonly reported mechanisms are cyp51A mediated. Using a unique series of A. fumigatus isolates, obtained from a patient suffering from persistent and recurrent invasive aspergillosis over 2 years, this study aimed to gain insight into the genetic basis of in-host adaptation. Single nucleotide polymorphisms (SNPs) unique to a single isolate in this series, which had developed multi-azole resistance in-host, were identified. Two nonsense SNPs were recreated using CRISPR-Cas9; these were 213* in svf1 and 167* in uncharacterised gene AFUA_7G01960. Phenotypic analyses including antifungal susceptibility testing, mycelial growth rate assessment, lipidomics analysis and statin susceptibility testing were performed to associate genotypes to phenotypes. T...
Source: Fungal Genetics and Biology - Category: Biology Authors: Tags: Fungal Genet Biol Source Type: research

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Conclusion: Higher MHR indicates an enhanced inflammation and oxidative stress which was not found to be associated with the presence of DPN. PMID: 31321988 [PubMed - as supplied by publisher]
Source: Future Medicine: Biomarkers in Medicine - Category: Internal Medicine Tags: Biomark Med Source Type: research
Publication date: Available online 19 July 2019Source: Biocatalysis and Agricultural BiotechnologyAuthor(s): Hafsa Sattar, Zainab Bibi, Aysha Kamran, Afsheen Aman, Shah Ali Ul QaderAbstractSerine metalloproteases have substantial scientific interest due to their unique physicochemical properties and capability to degrade complex casein polymer. In this contemporary study, the production of protease was enhanced by optimizing various physicochemical parameters and one-variable at a time approach used under submerged fermentation conditions. Among four different previously isolated Aspergillus species, Aspergillus niger KIBG...
Source: Biocatalysis and Agricultural Biotechnology - Category: Biotechnology Source Type: research
Publication date: Available online 19 July 2019Source: Protein Expression and PurificationAuthor(s): Elisabeth Graeber, Volodymyr M. KorkhovAbstractThe translocator protein TSPO is in an important diagnostic and therapeutic target in a range of pathologies, including neuroinflammation and cancer. Despite the availability of several structures of TSPO homologues, our understanding of the molecular determinants that govern high-affinity interactions of TSPO with its ligands is incomplete. Here, in order to decipher the key structural elements of TSPO responsible for interactions with its ligands, we designed a panel of chime...
Source: Protein Expression and Purification - Category: Biochemistry Source Type: research
ConclusionThese cases are reported because of their rare location and presentation since few cases of bilateral cholesterol granuloma have been reported in the literature.
Source: International Journal of Surgery Case Reports - Category: Surgery Source Type: research
Publication date: August 2019Source: Nutrition, Metabolism and Cardiovascular Diseases, Volume 29, Issue 8Author(s): Marialaura Bonaccio, Augusto Di Castelnuovo, Simona Costanzo, Mariarosaria Persichillo, Amalia De Curtis, Chiara Cerletti, Maria Benedetta Donati, Giovanni De Gaetano, Licia Iacoviello
Source: Nutrition, Metabolism and Cardiovascular Diseases - Category: Nutrition Source Type: research
Publication date: Available online 19 July 2019Source: Microbial PathogenesisAuthor(s): Tina Nasrin, Mousumi Patra, Mauricio Escudey, Tapan Kumar DasAbstractAimsE. coli is a widely known model organism for life science research, especially in modern bio-engineering and industrial microbiology. The goal of our current study is to understand the growth inhibitory mechanism of biosynthesized CdS nanoparticles on E. coli bacteria.Main methodsCharacterization of Aspergillus foetidus mediated CdS nanoparticles has been confirmed by Zeta potential, AFM and HRTEM analyses. Furthermore, we investigated the contribution of reactive ...
Source: Microbial Pathogenesis - Category: Infectious Diseases Source Type: research
Publication date: Available online 19 July 2019Source: Pharmacological ResearchAuthor(s): Chiara Pavanello, Andrea Baragetti, Adriana Branchi, Liliana Grigore, Samuela Castelnuovo, Eleonora Giorgio, Alberico L. Catapano, Laura Calabresi, Monica GomaraschiAbstractLysosomal acid lipase (LAL) is responsible for the hydrolysis of cholesteryl esters (CE) and triglycerides (TG) within the lysosomes; generated cholesterol and free fatty acids (FFA) are released in the cytosol where they can regulate their own synthesis and metabolism. When LAL is not active, as in case of genetic mutations, CE and TG accumulate in the lysosomal c...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
Authors: Pavić E, Hadžiabdić MO, Mucalo I, Martinis I, Romić Ž, Božikov V, Rahelić D Abstract This work aimed to evaluate and compare the benefits of the energy restricted Mediterranean diet (MD) and Standard hypolipemic diet (SHD) accompanied by exercise on metabolic syndrome parameters. A 12-month, randomized, single-blinded, diet-controlled study was conducted on 124 obese participants in the University Hospital Dubrava. Participants were assigned to the MD (n = 63) or the SHD (n = 61) and received the same amount of nutritional education and guidance on physical activity. The complet...
Source: International Journal for Vitamin and Nutrition Research - Category: Nutrition Tags: Int J Vitam Nutr Res Source Type: research
In conclusion, chronic restraint stress may induce esophageal fibrosis by accumulating ROS and increasing fibrotic gene expression in a murine model. PMID: 31316626 [PubMed]
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
Authors: Luo Y, Zheng M, Zhang Y, He S, Zhang L, Sun H, Liu X, Tan T, Zhu H, He J Abstract Patients with familial hypercholesterolemia usually present with high levels of serum low-density lipoprotein, xanthomas and early coronary artery disease. A 13 years old female patient was admitted to Children's Hospital of Chongqing Medical University presenting symptoms of heart failure. Laboratory tests showed that her cholesterol and low-density lipid levels were extremely high. Electrocardiogram test revealed that she had sinus tachycardia, QT lengthening and ST-T change. Multiple cardiac function abnormalities were dia...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
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