Characterisation of Aspergillus fumigatus Endocytic Trafficking within Airway Epithelial Cells Using High-Resolution Automated Quantitative Confocal Microscopy
AuthorsBen-Ghazzi, Nagwa; email: firstname.lastname@example.org
Moreno-Velásquez, Sergio; email: email@example.com
Seidel, Constanze; email: firstname.lastname@example.org
Thomson, Darren; orcid: 0000-0002-4800-7717; email: email@example.com
Denning, David W.; email: firstname.lastname@example.org
Read, Nick D.; email: email@example.com
Bowyer, Paul; email: firstname.lastname@example.org
Gago, Sara; orcid: 0000-0002-7027-4598; email: email@example.com
MetadataShow full item record
AbstractThe precise characterization of the mechanisms modulating Aspergillus fumigatus survival within airway epithelial cells has been impaired by the lack of live-cell imaging technologies and user-friendly quantification approaches. Here we described the use of an automated image analysis pipeline to estimate the proportion of A. fumigatus spores taken up by airway epithelial cells, those contained within phagolysosomes or acidified phagosomes, along with the fungal factors contributing to these processes. Coupling the use of fluorescent A. fumigatus strains and fluorescent epithelial probes targeting lysosomes, acidified compartments and cell membrane, we found that both the efficacy of lysosome recruitment to phagosomes and phagosome acidification determines the capacity of airway epithelial cells to contain A. fumigatus growth. Overall, the capability of the airway epithelium to prevent A. fumigatus survival was higher in bronchial epithelial than alveolar epithelial cells. Certain A. fumigatus cell wall mutants influenced phagosome maturation in airway epithelial cells. Taken together, this live-cell 4D imaging approach allows observation and measurement of the very early processes of A. fumigatus interaction within live airway epithelial monolayers.
CitationJournal of Fungi, volume 7, issue 6, page e454
DescriptionFrom MDPI via Jisc Publications Router
History: accepted 2021-06-02, pub-electronic 2021-06-07
Publication status: Published
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research; Grant(s): NC/P002390/1
Funder: German Science Fundation; Grant(s): DFG, SE2405/1-1
Funder: Libyan Ministry of Higher Education and Scientific Research; Grant(s): NA
Funder: Consejo Nacional de Ciencia y Tecnología; Grant(s): 359173
Funder: NIHR Manchester Biomedical Research Centre; Grant(s): NA
Funder: FP7 Ideas: European Research Council; Grant(s): PITN-GA-520 2013-607963
Showing items related by title, author, creator and subject.
Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?Park, JooYong; email: firstname.lastname@example.org; Choi, Ji-Yeob; email: email@example.com; Choi, Jaesung; email: firstname.lastname@example.org; Chung, Seokang; email: email@example.com; Song, Nan; orcid: 0000-0002-9182-1060; email: firstname.lastname@example.org; Park, Sue K.; orcid: 0000-0001-5002-9707; email: email@example.com; Han, Wonshik; email: firstname.lastname@example.org; Noh, Dong-Young; email: email@example.com; Ahn, Sei-Hyun; email: firstname.lastname@example.org; Lee, Jong Won; email: email@example.com; et al. (MDPI, 2021-05-14)In this study we aim to examine gene–environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10−3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10−4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.
Strategies to Improve Antimicrobial Utilization with a Special Focus on Developing CountriesGodman, Brian; orcid: 0000-0001-6539-6972; email: firstname.lastname@example.org; Egwuenu, Abiodun; orcid: 0000-0002-9369-4771; email: email@example.com; Haque, Mainul; orcid: 0000-0002-6124-7993; email: firstname.lastname@example.org; Malande, Oliver Ombeva; email: email@example.com; Schellack, Natalie; email: firstname.lastname@example.org; Kumar, Santosh; orcid: 0000-0002-5117-7872; email: email@example.com; Saleem, Zikria; orcid: 0000-0003-3202-6347; email: firstname.lastname@example.org; Sneddon, Jacqueline; email: email@example.com; Hoxha, Iris; email: firstname.lastname@example.org; Islam, Salequl; email: email@example.com; et al. (MDPI, 2021-06-07)Antimicrobial resistance (AMR) is a high priority across countries as it increases morbidity, mortality and costs. Concerns with AMR have resulted in multiple initiatives internationally, nationally and regionally to enhance appropriate antibiotic utilization across sectors to reduce AMR, with the overuse of antibiotics exacerbated by the COVID-19 pandemic. Effectively tackling AMR is crucial for all countries. Principally a narrative review of ongoing activities across sectors was undertaken to improve antimicrobial use and address issues with vaccines including COVID-19. Point prevalence surveys have been successful in hospitals to identify areas for quality improvement programs, principally centering on antimicrobial stewardship programs. These include reducing prolonged antibiotic use to prevent surgical site infections. Multiple activities centering on education have been successful in reducing inappropriate prescribing and dispensing of antimicrobials in ambulatory care for essentially viral infections such as acute respiratory infections. It is imperative to develop new quality indicators for ambulatory care given current concerns, and instigate programs with clear public health messaging to reduce misinformation, essential for pandemics. Regular access to effective treatments is needed to reduce resistance to treatments for HIV, malaria and tuberculosis. Key stakeholder groups can instigate multiple initiatives to reduce AMR. These need to be followed up.
Discovery and Evaluation of Protein Biomarkers as a Signature of Wellness in Late-Stage Cancer Patients in Early Phase Clinical TrialsGeary, Bethany; orcid: 0000-0002-5592-5532; email: firstname.lastname@example.org; Peat, Erin; email: email@example.com; Dransfield, Sarah; email: firstname.lastname@example.org; Cook, Natalie; orcid: 0000-0003-2606-1082; email: email@example.com; Thistlethwaite, Fiona; orcid: 0000-0002-4832-7008; email: firstname.lastname@example.org; Graham, Donna; email: email@example.com; Carter, Louise; email: firstname.lastname@example.org; Hughes, Andrew; email: Andrew.email@example.com; Krebs, Matthew G.; email: firstname.lastname@example.org; Whetton, Anthony D.; orcid: 0000-0002-1098-3878; email: email@example.com (MDPI, 2021-05-18)TARGET (tumour characterisation to guide experimental targeted therapy) is a cancer precision medicine programme focused on molecular characterisation of patients entering early phase clinical trials. Performance status (PS) measures a patient’s ability to perform a variety of activities. However, the quality of present algorithms to assess PS is limited and based on qualitative clinician assessment. Plasma samples from patients enrolled into TARGET were analysed using the mass spectrometry (MS) technique: sequential window acquisition of all theoretical fragment ion spectra (SWATH)-MS. SWATH-MS was used on a discovery cohort of 55 patients to differentiate patients into either a good or poor prognosis by creation of a Wellness Score (WS) that showed stronger prediction of overall survival (p = 0.000551) compared to PS (p = 0.001). WS was then tested against a validation cohort of 77 patients showing significant (p = 0.000451) prediction of overall survival. WS in both sets had receiver operating characteristic curve area under the curve (AUC) values of 0.76 (p = 0.002) and 0.67 (p = 0.011): AUC of PS was 0.70 (p = 0.117) and 0.55 (p = 0.548). These signatures can now be evaluated further in larger patient populations to assess their utility in a clinical setting.