Project description:Antibiotic resistance genes expressed in the upper respiratory tract of patients infected with influenza viruses were associated with the microbial community and microbial activities. Interactions between the host systemic responses to influenza infection and ARG expression highlight the importance of antibiotic resistance in viral-bacterial co-infection.
Project description:Antibiotic resistance genes expressed in the upper respiratory tract of patients infected with influenza viruses were associated with the microbial community and microbial activities. Interactions between the host systemic responses to influenza infection and ARG expression highlight the importance of antibiotic resistance in viral-bacterial co-infection.
Project description:Antibiotic resistance genes expressed in the upper respiratory tract of patients infected with influenza viruses were associated with the microbial community and microbial activities. Interactions between the host systemic responses to influenza infection and ARG expression highlight the importance of antibiotic resistance in viral-bacterial co-infection.
Project description:The upper respiratory tract (nasopharynx or NP) is the first site of influenza replication, allowing the virus to disseminate to the lower respiratory tract or promoting community transmission. The host response in the NP regulates an intricate balance between viral control and tissue pathology. The hyper-inflammatory responses promote epithelial injury, allowing for increased viral dissemination and susceptibility to secondary bacterial infections. However, the pathologic contributors to influenza upper respiratory tissue pathology are incompletely understood. In this study, we investigated the role of IL-17RA as a modulator of influenza host response and inflammation in the upper respiratory tract. We used a combined experimental approach involving IL-17RA-/- mice and an air-liquid interface (ALI) epithelial culture model to investigate the role of IL-17 response in epithelial inflammation, barrier function, and tissue pathology. Our data show that IL-17RA-/- mice exhibited significantly reduced neutrophilia, epithelial injury, and viral load. The reduced NP inflammation and epithelial injury in IL-17RA-/- mice correlated with increased resistance against co-infection by Streptococcus pneumoniae (Spn). IL-17A treatment, while potentiating the apoptosis of IAV-infected epithelial cells, caused bystander cell death and disrupted the barrier function in ALI epithelial model, supporting the in vivo findings.
Project description:Respiratory-tract infections are a predominant cause for clinical treatment, although, clinical assessments and standard clinical laboratory protocols are time-consuming and often inadequate for reliable diagnoses. Novel methods, preferably applied directly to clinical samples, excluding cultivation steps, are needed to improve diagnostics, provide adequate treatment and reduce the use of antibiotics and associated development of antibiotic resistance. This study applied nano-liquid chromatography coupled with tandem MS, with a bioinformatics pipeline and an in-house database of curated high-quality reference genome sequences to identify species-unique peptides as potential biomarkers for bacterial pathogens commonly found in respiratory tract infections: Staphylococcus aureus; Moraxella catarrhalis; Haemophilus influenzae and Streptococcus pneumoniae. The species-unique peptides were initially identified in pure-culture bacterial reference strains, reflecting the genomic variation in the four species and, furthermore in clinical respiratory tract samples, without prior cultivation, elucidating proteins expressed in clinical conditions of infection. Peptide biomarker candidates for each species is presented. As a proof-of-principle, the most promising species-unique peptides were applied in targeted tandem MS-analyses of clinical samples and their relevance for identifications of the pathogens, i.e. proteotyping, was validated, demonstrating their potential as effective peptide biomarker candidates for diagnostics of infectious diseases.
