A5015372087- Antifungal resistance and susceptibility
- Asthma and respiratory diseases
- Allergic Rhinitis and Sensitization
- Fungal Infections and Studies
- RNA Research and Splicing
- Fungal and yeast genetics research
- Plant Pathogens and Fungal Diseases
- RNA modifications and cancer
- Mycotoxins in Agriculture and Food
- Cancer-related molecular mechanisms research
- RNA and protein synthesis mechanisms
- Food Allergy and Anaphylaxis Research
- Pneumonia and Respiratory Infections
- Pneumocystis jirovecii pneumonia detection and treatment
- Fungal Biology and Applications
- HIV/AIDS drug development and treatment
- CRISPR and Genetic Engineering
- Plant and Fungal Interactions Research
- Complement system in diseases
- Infectious Diseases and Mycology
- Peptidase Inhibition and Analysis
- Pharmacogenetics and Drug Metabolism
- Genomics and Chromatin Dynamics
- Molecular Biology Techniques and Applications
- Tuberculosis Research and Epidemiology
University of Manchester
2013-2022
Genomics (United Kingdom)
2022
Pavia nel Cuore
2019
Manchester Academic Health Science Centre
2010-2017
Manchester University NHS Foundation Trust
2017
Manchester University
2015
Allergy Therapeutics (United Kingdom)
2014
Wythenshawe Hospital
2006
Oral triazole therapy is well established for the treatment of invasive (IPA), allergic (ABPA), and chronic pulmonary (CPA) aspergillosis, often long-term. Triazole resistance rates are rising internationally. Microbiological diagnosis aspergillosis limited by poor culture yield, leading to uncertainty about frequency resistance.
ObjectivesRecent increases in triazole resistance Aspergillus fumigatus have been attributed primarily to target site (cyp51A) mutations. A recent survey of resistant isolates Manchester showed that >50% had no mutation cyp51A or its promoter. We investigated the mechanisms clinical azole-resistant without
Abstract The frequency of antifungal resistance, particularly to the azole class ergosterol biosynthetic inhibitors, is a growing global health problem. Survival rates for those infected with resistant isolates are exceptionally low. Beyond modification drug target, our understanding molecular basis resistance in fungal pathogen Aspergillus fumigatus limited. We reasoned that clinically relevant could derive from transcriptional rewiring, promoting without concomitant reductions...
Summary Diagnosis of aspergillosis is often difficult. We compared fungal yields from respiratory specimens using the Health Protection Agency standard culture method ( BSOP 57), a higher volume undiluted Mycology Reference Centre Manchester MRCM ) and Aspergillus quantitative real time polymerase chain reaction (q PCR ). Sputum, bronchial aspirate bronchoalveolar lavage BAL samples (total 23) were collected patients. One fraction all was cultured method, one 57 used for q . The recovery...
In susceptible individuals, exposure to Aspergillus fumigatus can lead the development of atopic lung diseases such as allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS). Protease allergens including Asp f 5 13 from are thought be important for initiation progression asthma.To assess importance secreted protease (matrix metalloprotease) (serine protease) in fumigatus-induced inflammation, airway hyperactivity, atopy wall remodelling a murine...
Aspergillus fumigatus is a human pathogen and the principal etiologic agent of invasive chronic aspergillosis leading to several hundreds thousands deaths every year. Very few antifungals are available treat infections caused by A. fumigatus, resistance developing those we have. Our understanding molecular mechanisms that drive pathogenicity drug have been hampered lack large mutant collections, which limits our ability perform functional genomics analysis. Here present high-throughput gene...
Allergy is a common debilitating and occasionally life threatening condition. The fungal kingdom contains number of species that produce wide range well defined protein allergens although the vast majority have unknown allergenic potential. recent genome sequencing variety fungi provides opportunity to assess occurrence allergen orthologues across kingdom. Here we use comparative genomics survey in fungi. A database 82 sequences was compiled used search 22 genomes. Additionally were able...
Recent estimates of the global burden fungal disease suggest that their incidence has been drastically underestimated and mortality may rival malaria or tuberculosis. Azoles are principal class antifungal drug only available oral treatment for disease. occurrence increase in azole resistance is a major concern worldwide. Known mechanisms include over-expression efflux pumps mutation gene encoding target protein cyp51a, however, one most important pathogens humans, Aspergillus fumigatus, much...
Noncoding RNAs (ncRNAs) are emerging as key regulators of cellular function. We have exploited the recently developed barcoded ncRNA gene deletion strain collections in yeast Saccharomyces cerevisiae to investigate numerous ncRNAs with no known The collection contains deletions tRNAs, snoRNAs, snRNAs, stable unannotated transcripts (SUTs), cryptic unstable (CUTs) and other annotated encompassing 532 different individual deletions. profiled fitness diploid heterozygous six conditions using...
Inhibition of fungal growth by Congo red (CR) has been putatively associated with specific binding to β-1,3-glucans, which blocks cell wall polysaccharide synthesis. In this study, we searched for transcription factors (TFs) that regulate the response CR and interrogated their regulon. During investigation susceptibility TF mutant library, several CR-resistant -hypersensitive mutants were discovered further studied. Abnormal distorted swollen conidia called Quasimodo cells seen in presence...
Abstract Aspergillus fumigatus is an opportunistic human pathogenic mold. DNA extraction from this fungus usually performed by mechanical perturbation of cells, as it possesses a rigid and complex cell wall. While not problematic for single isolates, can be time consuming large numbers strains if using traditional procedures. Therefore, in article we describe fast efficient thermal‐shock method to release spores A. other filamentous fungi without the need methods. This especially important...
Non-coding RNAs (ncRNAs), including the more recently identified Stable Unannotated Transcripts (SUTs) and Cryptic Unstable (CUTs), are increasingly being shown to play pivotal roles in transcriptional post-transcriptional regulation of genes eukaryotes. Here, we carried out a large-scale screening ncRNAs Saccharomyces cerevisiae , provide evidence for SUT CUT function. Phenotypic data on 372 ncRNA deletion strains 23 different growth conditions were collected, identifying responsible...
Summary Several studies suggest mannose‐binding lectin (MBL) deficiency is associated with various manifestations of aspergillosis. MBL serum levels and function are genetically determined, but rise during inflammation. We address the relative frequency deficient genotypes, relationship between level genotype both age disease in patients chronic pulmonary (CPA) allergic bronchopulmonary aspergillosis (ABPA) severe asthma fungal sensitization (SAFS). DNA was extracted from blood samples, MBL2...
ABSTRACT Azole resistance is an increasing clinical problem for Aspergillus fumigatus , with the majority of published arising from mutations in azole target gene CYP51A. Previous structural studies this protein have suffered a nonorthologous, low-homology template homology modeling. Here we present new model based on human CYP51A orthologue that provides higher-quality A.
Abstract The pathogenic fungus Aspergillus fumigatus is a major etiological agent of fungal invasive and chronic diseases affecting tens millions individuals worldwide. Draft genome sequences two clinical isolates (Af293 A1163) are commonly used as reference genomes for analyses environmental strains. However, the lack coverage centromeres, an accurate sequence ribosomal repeats, comprehensive annotation chromosomal rearrangements such translocations inversions. Here, we PacBio Single...
The opportunistic fungus Pneumocystis jirovecii causes pneumonia (PcP), which is a life-threatening infection in HIV/AIDS patients. seemingly low prevalence of P. sub-Saharan Africa has been matter great debate because many patients reside this region. lack suitable diagnostic practices resource limited-region added to the uncertainty PcP prevalence. Only few studies have evaluated utility easily obtainable samples such as expectorated sputum for diagnosis PcP. Thus, aim current study was...
Eukaryotic genomes are extensively transcribed, generating many different RNAs with no known function. We have constructed 1502 molecular barcoded ncRNA gene deletion strains encompassing 443 ncRNAs in the yeast Saccharomyces cerevisiae as tools for functional analysis. This resource includes deletions of small nuclear (snRNAs), transfer (tRNAs), nucleolar (snoRNAs), and other annotated well more recently identified stable unannotated transcripts (SUTs) cryptic unstable (CUTs) whose...
A. fumigatus has been associated with a wide spectrum of allergic disorders such as ABPA or SAFS. It is poorly understood what allergens in particular are being expressed during fungal invasion and which responsible for stimulation immune responses. Study the dynamics allergen production by fungi may lead to insights into how presented system.Expression 17 genes was examined response various culture conditions stimuli well presence macrophages order mimic encountered lung.Expression 14/17...
<b>Background:</b> Microbiota may contribute to pathophysiologic processes in airway disease. However, the effect on asthma severity fungal associated is unclear. We studied microbiome severe (SA), with sensitisation (SAFS), ABPA, mild (MA). <b>Methods:</b> analysed BAL of 59 patients SA (n=11), SAFS (n=16), ABPA(n=16), MA(n=6) and NH(n=6) by culture bacterial (16S & 23S) (ITS1-5S 28S) sequencing. <b>Results:</b> Fungi were cultured 17 (28.8%); ABPA 6 (37.5%), 9 (60%), 2 (9%). Sequencing...