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  • 1
    Online Resource
    Online Resource
    How antibiotic resistance is shaped by host-microbiome interactions in influenza
    Springer Science and Business Media LLC ; 2020
    In:  Microbiome Vol. 8, No. 1 ( 2020-12)
    Details
    In: Microbiome, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2020-12)
    Abstract: The abundance and diversity of antibiotic resistance genes (ARGs) in the human respiratory microbiome remain poorly characterized. In the context of influenza virus infection, interactions between the virus, the host, and resident bacteria with pathogenic potential are known to complicate and worsen disease, resulting in coinfection and increased morbidity and mortality of infected individuals. When pathogenic bacteria acquire antibiotic resistance, they are more difficult to treat and of global health concern. Characterization of ARG expression in the upper respiratory tract could help better understand the role antibiotic resistance plays in the pathogenesis of influenza-associated bacterial secondary infection. Results Thirty-seven individuals participating in the Household Influenza Transmission Study (HITS) in Managua, Nicaragua, were selected for this study. We performed metatranscriptomics and 16S rRNA gene sequencing analyses on nasal and throat swab samples, and host transcriptome profiling on blood samples. Individuals clustered into two groups based on their microbial gene expression profiles, with several microbial pathways enriched with genes differentially expressed between groups. We also analyzed antibiotic resistance gene expression and determined that approximately 25% of the sequence reads that corresponded to antibiotic resistance genes mapped to Streptococcus pneumoniae and Staphylococcus aureus . Following construction of an integrated network of ARG expression with host gene co-expression, we identified several host key regulators involved in the host response to influenza virus and bacterial infections, and host gene pathways associated with specific antibiotic resistance genes. Conclusions This study indicates the host response to influenza infection could indirectly affect antibiotic resistance gene expression in the respiratory tract by impacting the microbial community structure and overall microbial gene expression. Interactions between the host systemic responses to influenza infection and antibiotic resistance gene expression highlight the importance of viral-bacterial co-infection in acute respiratory infections like influenza.
    Type of Medium: Online Resource
    ISSN: 2049-2618
    URL: Article
    URL: Article
    DOI: 10.1186/s40168-020-00803-2
    DOI: 10.21203/rs.3.rs-27126/v1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2697425-3
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  • 2
    Online Resource
    Online Resource
    Functional lower airways genomic profiling of the microbiome to capture active microbial metabolism
    European Respiratory Society (ERS) ; 2021
    In:  European Respiratory Journal Vol. 58, No. 1 ( 2021-07), p. 2003434-
    Details
    In: European Respiratory Journal, European Respiratory Society (ERS), Vol. 58, No. 1 ( 2021-07), p. 2003434-
    Abstract: Microbiome studies of the lower airways based on bacterial 16S rRNA gene sequencing assess microbial community structure but can only infer functional characteristics. Microbial products, such as short-chain fatty acids (SCFAs), in the lower airways have significant impact on the host's immune tone. Thus, functional approaches to the analyses of the microbiome are necessary. Methods Here we used upper and lower airway samples from a research bronchoscopy smoker cohort. In addition, we validated our results in an experimental mouse model. We extended our microbiota characterisation beyond 16S rRNA gene sequencing with the use of whole-genome shotgun (WGS) and RNA metatranscriptome sequencing. SCFAs were also measured in lower airway samples and correlated with each of the sequencing datasets. In the mouse model, 16S rRNA gene and RNA metatranscriptome sequencing were performed. Results Functional evaluations of the lower airway microbiota using inferred metagenome, WGS and metatranscriptome data were dissimilar. Comparison with measured levels of SCFAs shows that the inferred metagenome from the 16S rRNA gene sequencing data was poorly correlated, while better correlations were noted when SCFA levels were compared with WGS and metatranscriptome data. Modelling lower airway aspiration with oral commensals in a mouse model showed that the metatranscriptome most efficiently captures transient active microbial metabolism, which was overestimated by 16S rRNA gene sequencing. Conclusions Functional characterisation of the lower airway microbiota through metatranscriptome data identifies metabolically active organisms capable of producing metabolites with immunomodulatory capacity, such as SCFAs.
    Type of Medium: Online Resource
    ISSN: 0903-1936 , 1399-3003
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.1183/13993003.03434-2020
    DOI: 10.1183/13993003.03434-2020.Supp1
    DOI: 10.1183/13993003.03434-2020.Shareable1
    Language: English
    Publisher: European Respiratory Society (ERS)
    Publication Date: 2021
    detail.hit.zdb_id: 2834928-3
    detail.hit.zdb_id: 1499101-9
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  • 3
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    Online Resource
    Microbial Composition of the Human Nasopharynx Varies According to Influenza Virus Type and Vaccination Status
    American Society for Microbiology ; 2019
    In:  mBio Vol. 10, No. 4 ( 2019-08-27)
    Details
    In: mBio, American Society for Microbiology, Vol. 10, No. 4 ( 2019-08-27)
    Abstract: Factors that contribute to enhanced susceptibility to severe bacterial disease after influenza virus infection are not well defined but likely include the microbiome of the respiratory tract. Vaccination against influenza, while having variable effectiveness, could also play a role in microbial community stability. We collected nasopharyngeal samples from 215 individuals infected with influenza A/H3N2 or influenza B virus and profiled the microbiota by target sequencing of the 16S rRNA gene. We identified signature taxonomic groups by performing linear discriminant analysis and effective size comparisons (LEfSe) and defined bacterial community types using Dirichlet multinomial mixture (DMM) models. Influenza infection was shown to be significantly associated with microbial composition of the nasopharynx according to the virus type and the vaccination status of the patient. We identified four microbial community types across the combined cohort of influenza patients and healthy individuals with one community type most representative of the influenza virus-infected group. We also identified microbial taxa for which relative abundance was significantly higher in the unvaccinated elderly group; these taxa include species known to be associated with pneumonia. IMPORTANCE Our results suggest that there is a significant association between the composition of the microbiota in the nasopharynx and the influenza virus type causing the infection. We observe that vaccination status, especially in more senior individuals, also has an association with the microbial community profile. This indicates that vaccination against influenza, even when ineffective to prevent disease, could play a role in controlling secondary bacterial complications.
    Type of Medium: Online Resource
    ISSN: 2161-2129 , 2150-7511
    URL: Article
    DOI: 10.1128/mBio.01296-19
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2019
    detail.hit.zdb_id: 2557172-2
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  • 4
    Online Resource
    Online Resource
    CRISPR arrays as high-resolution markers to track microbial transmission during influenza infection
    Springer Science and Business Media LLC ; 2023
    In:  Microbiome Vol. 11, No. 1 ( 2023-06-17)
    Details
    In: Microbiome, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2023-06-17)
    Abstract: Disruption of the microbial community in the respiratory tract due to infections, like influenza, could impact transmission of bacterial pathogens. Using samples from a household study, we determined whether metagenomic-type analyses of the microbiome provide the resolution necessary to track transmission of airway bacteria. Microbiome studies have shown that the microbial community across various body sites tends to be more similar between individuals who cohabit in the same household than between individuals from different households. We tested whether there was increased sharing of bacteria from the airways within households with influenza infections as compared to control households with no influenza. Results We obtained 221 respiratory samples that were collected from 54 individuals at 4 to 5 time points across 10 households, with and without influenza infection, in Managua, Nicaragua. From these samples, we generated metagenomic (whole genome shotgun sequencing) datasets to profile microbial taxonomy. Overall, specific bacteria and phages were differentially abundant between influenza positive households and control (no influenza infection) households, with bacteria like Rothia , and phages like Staphylococcus P68virus that were significantly enriched in the influenza-positive households. We identified CRISPR spacers detected in the metagenomic sequence reads and used these to track bacteria transmission within and across households. We observed a clear sharing of bacterial commensals and pathobionts, such as Rothia , Neisseria , and Prevotella , within and between households. However, due to the relatively small number of households in our study, we could not determine if there was a correlation between increased bacterial transmission and influenza infection. Conclusion We observed that airway microbial composition differences across households were associated with what appeared to be different susceptibility to influenza infection. We also demonstrate that CRISPR spacers from the whole microbial community can be used as markers to study bacterial transmission between individuals. Although additional evidence is needed to study transmission of specific bacterial strains, we observed sharing of respiratory commensals and pathobionts within and across households.
    Type of Medium: Online Resource
    ISSN: 2049-2618
    URL: Article
    DOI: 10.1186/s40168-023-01568-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2697425-3
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