Project description:Sub-Saharan Africa represents 69% of the total number of individuals living with HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a common and frequently fatal complication, though little is known regarding the lower airway microbiome composition of this population. Our objectives were to characterize the lower airway microbiome of Ugandan HIV-infected patients with pneumonia, to determine relationships with demographic, clinical, immunological, and microbiological variables and to compare the composition and predicted metagenome of these communities to a comparable cohort of patients in the US (San Francisco). Bronchoalveolar lavage samples from a cohort of 60 Ugandan HIV-infected patients with acute pneumonia were collected. Amplified 16S ribosomal RNA was profiled and aforementioned relationships examined. Ugandan airway microbiome composition and predicted metagenomic function were compared to US HIV-infected pneumonia patients. Among the most common bacterial pulmonary pathogens, Pseudomonas aeruginosa was most prevalent in the Ugandan cohort. Patients with a richer and more diverse airway microbiome exhibited lower bacterial burden, enrichment of members of the Lachnospiraceae and sulfur-reducing bacteria and reduced expression of TNF-alpha and matrix metalloproteinase-9. Compared to San Franciscan patients, Ugandan airway microbiome were significantly richer, and compositionally distinct with predicted metagenomes that encoded a multitude of distinct pathogenic pathways e.g secretion systems. Ugandan pneumonia-associated airway microbiome is compositionally and functionally distinct from those detected in comparable patients in developed countries, a feature which may contribute to adverse outcomes in this population. Please note that the data from the comparable cohort of patients in the USUS data was published as supplemental material of PMID: 22760045 but not submitted to GEO The 'patient_info.txt' contains 12 clinical, 7 immunological and 3 microbiological variables for each patient. The G2 PhyloChip microarray platform (commercially available from Second Genome, Inc.) was used to profile bacteria in lower airway samples from 60 subjects
Project description:Sub-Saharan Africa represents 69% of the total number of individuals living with HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a common and frequently fatal complication, though little is known regarding the lower airway microbiome composition of this population. Our objectives were to characterize the lower airway microbiome of Ugandan HIV-infected patients with pneumonia, to determine relationships with demographic, clinical, immunological, and microbiological variables and to compare the composition and predicted metagenome of these communities to a comparable cohort of patients in the US (San Francisco). Bronchoalveolar lavage samples from a cohort of 60 Ugandan HIV-infected patients with acute pneumonia were collected. Amplified 16S ribosomal RNA was profiled and aforementioned relationships examined. Ugandan airway microbiome composition and predicted metagenomic function were compared to US HIV-infected pneumonia patients. Among the most common bacterial pulmonary pathogens, Pseudomonas aeruginosa was most prevalent in the Ugandan cohort. Patients with a richer and more diverse airway microbiome exhibited lower bacterial burden, enrichment of members of the Lachnospiraceae and sulfur-reducing bacteria and reduced expression of TNF-alpha and matrix metalloproteinase-9. Compared to San Franciscan patients, Ugandan airway microbiome were significantly richer, and compositionally distinct with predicted metagenomes that encoded a multitude of distinct pathogenic pathways e.g secretion systems. Ugandan pneumonia-associated airway microbiome is compositionally and functionally distinct from those detected in comparable patients in developed countries, a feature which may contribute to adverse outcomes in this population. Please note that the data from the comparable cohort of patients in the USUS data was published as supplemental material of PMID: 22760045 but not submitted to GEO The 'patient_info.txt' contains 12 clinical, 7 immunological and 3 microbiological variables for each patient.
Project description:We sought to determine how gene expression changes during the first two years of HIV-1 infection among participants from HIV-1 serodiscordant couple cohorts from sub-Saharan Africa. This study included whole blood samples from 26 participants who did not have HIV-1 at study enrollment, had a steady sexual relationship with a partner with HIV-1 and acquired HIV-1 during follow-up. Most participants had samples from before and after infection.
Project description:Chronic Obstructive Pulmonary Disease (COPD) is increasingly prevalent among people infected with human immunodeficiency virus (HIV) in sub-Saharan Africa, yet the ecological and immunological mechanisms linking airway microbes to mucosal inflammation remain unclear. We performed multi-omics profiling in adults from rural Uganda stratified by their HIV and COPD status, integrating sputum microbiome sequencing, outer membrane vesicle quantification, cytokine profiling, cytometry by time-of flight immunophenotyping, and bulk and single-cell transcriptomics with bronchoalveolar lavage-guided deconvolution. Temporal ecological dynamics predominantly shaped airway microbial structure, although disease-modified instability patterns, particularly Haemophilus enrichment and altered trajectories of Staphylococcus, Gemella, and Moraxella, were detectable in HIV+/COPD+ individuals. In contrast, host immune phenotypes showed disease-linked remodeling: HIV and COPD were associated with activation of NF-κB, IL-17, chemokine, TLR, NOD, and antiviral pathways and with compartment-specific transcriptional shifts across sputum, bronchoalveolar lavage, and blood. Integrative modeling revealed discrete, non-linear microbe-immune interaction modules rather than broad dysbiosis, indicating that specific taxa engage defined inflammatory circuits. Together, these findings suggest that HIV-associated COPD reflects immune-skewed mucosal remodeling in which the airway microbiome functions as a selective, temporally dynamic modulator of inflammatory states rather than a globally disrupted community.
Project description:Chronic Obstructive Pulmonary Disease (COPD) is increasingly prevalent among people infected with human immunodeficiency virus (HIV) in sub-Saharan Africa, yet the ecological and immunological mechanisms linking airway microbes to mucosal inflammation remain unclear. We performed multi-omics profiling in adults from rural Uganda stratified by their HIV and COPD status, integrating sputum microbiome sequencing, outer membrane vesicle quantification, cytokine profiling, cytometry by time-of flight immunophenotyping, and bulk and single-cell transcriptomics with bronchoalveolar lavage-guided deconvolution. Temporal ecological dynamics predominantly shaped airway microbial structure, although disease-modified instability patterns, particularly Haemophilus enrichment and altered trajectories of Staphylococcus, Gemella, and Moraxella, were detectable in HIV+/COPD+ individuals. In contrast, host immune phenotypes showed disease-linked remodeling: HIV and COPD were associated with activation of NF-κB, IL-17, chemokine, TLR, NOD, and antiviral pathways and with compartment-specific transcriptional shifts across sputum, bronchoalveolar lavage, and blood. Integrative modeling revealed discrete, non-linear microbe-immune interaction modules rather than broad dysbiosis, indicating that specific taxa engage defined inflammatory circuits. Together, these findings suggest that HIV-associated COPD reflects immune-skewed mucosal remodeling in which the airway microbiome functions as a selective, temporally dynamic modulator of inflammatory states rather than a globally disrupted community.
Project description:Non-typhoidal Salmonella serotypes (NTS) cause a self-limited gastroenteritis while pediatric patients with severe Plasmodium falciparum malaria can develop a life threatening bacteremia that is a major source of child mortality in sub-Saharan Africa. We used microarrays to detail genome-scale gene expression profiles underlying gastrointestinal immune responses to bacterial infection in mice
Project description:Sorghum bicolor is one of the most important cereal crops in the world, predominantly grown in sub‑Saharan Africa by smallholder farmers. Despite its outstanding resilience to abiotic stresses, approximately 20% of sorghum yield is annually lost on the African continent due to infestation with the parasitic weed Striga hermonthica. Existing Striga management strategies to decrease Striga infestation often show low efficiency and are not easily integrated into current agricultural practices. Microbial-based solutions may prove an effective, low-cost mode for reducing Striga parasitism in sub-Saharan Africa. Here, we demonstrate that the microbiome component of a field soil suppresses Striga infection of sorghum. Potential mechanisms underlying the soil microbiome’s influence on the host plant include root endodermal suberization and aerenchyma formation. Moreover, we observed a depletion of haustorium inducing factors, compounds essential for Striga to establish the host-parasite association, in root exudates collected from sorghum grown in the presence of the soil microbiome as compared to sterile conditions. We further identified individual microbial taxa associated with reduced Striga infection via changes in root cellular anatomy and differentiation as well as in exudate composition. Our study identifies a suite of traits that can be harnessed by individual microbial isolates or their consortia to induce Striga resistance. Combining microbes that elicit Striga resistance directly (affecting the parasite) via repression of haustorium formation with those that act indirectly (affecting the host), by reducing of Striga penetration through root tissue, can broaden the effectiveness of microbe-induced protection from Striga.