Browsing by Author "Paulson, Joseph N."
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Item Longitudinal analysis of the lung microbiota of cynomolgous macaques during long-term SHIV infection(Springer Nature, 2016-07-08) Morris, Alison; Paulson, Joseph N.; Talukder, Hisham; Tipton, Laura; Kling, Heather; Cui, Lijia; Fitch, Adam; Pop, Mihai; Norris, Karen A.; Ghedin, ElodieLongitudinal studies of the lung microbiome are challenging due to the invasive nature of sample collection. In addition, studies of the lung microbiome in human disease are usually performed after disease onset, limiting the ability to determine early events in the lung. We used a non-human primate model to assess lung microbiome alterations over time in response to an HIV-like immunosuppression and determined impact of the lung microbiome on development of obstructive lung disease. Cynomolgous macaques were infected with the SIV-HIV chimeric virus SHIV89.6P. Bronchoalveolar lavage fluid samples were collected pre-infection and every 4 weeks for 53 weeks post-infection. The microbiota was characterized at each time point by 16S ribosomal RNA (rRNA) sequencing. We observed individual variation in the composition of the lung microbiota with a proportion of the macaques having Tropheryma whipplei as the dominant organism in their lungs. Bacterial communities varied over time both within and between animals, but there did not appear to be a systematic alteration due to SHIV infection. Development of obstructive lung disease in the SHIV-infected animals was characterized by a relative increase in abundance of oral anaerobes. Network analysis further identified a difference in community composition that accompanied the development of obstructive disease with negative correlations between members of the obstructed and non-obstructed groups. This emphasizes how species shifts can impact multiple other species, potentially resulting in disease. This study is the first to investigate the dynamics of the lung microbiota over time and in response to immunosuppression in a non-human primate model. The persistence of oral bacteria in the lung and their association with obstruction suggest a potential role in pathogenesis. The lung microbiome in the non-human primate is a valuable tool for examining the impact of the lung microbiome in human health and disease.Item Mentholation affects the cigarette microbiota by selecting for bacteria resistant to harsh environmental conditions and selecting against potential bacterial pathogens(Springer Nature, 2017-02-15) Chopyk, Jessica; Chattopadhyay, Suhana; Kulkarni, Prachi; Claye, Emma; Babik, Kelsey R.; Reid, Molly C.; Smyth, Eoghan M.; Hittle, Lauren E.; Paulson, Joseph N.; Cruz-Cano, Raul; Pop, Mihai; Buehler, Stephanie S.; Clark, Pamela I.; Sapkota, Amy R.; Mongodin, Emmanuel F.There is a paucity of data regarding the microbial constituents of tobacco products and their impacts on public health. Moreover, there has been no comparative characterization performed on the bacterial microbiota associated with the addition of menthol, an additive that has been used by tobacco manufacturers for nearly a century. To address this knowledge gap, we conducted bacterial community profiling on tobacco from user- and custom-mentholated/non-mentholated cigarette pairs, as well as a commercially-mentholated product. Total genomic DNA was extracted using a multi-step enzymatic and mechanical lysis protocol followed by PCR amplification of the V3-V4 hypervariable regions of the 16S rRNA gene from five cigarette products (18 cigarettes per product for a total of 90 samples): Camel Crush, user-mentholated Camel Crush, Camel Kings, custom-mentholated Camel Kings, and Newport Menthols. Sequencing was performed on the Illumina MiSeq platform and sequences were processed using the Quantitative Insights Into Microbial Ecology (QIIME) software package. In all products, Pseudomonas was the most abundant genera and included Pseudomonas oryzihabitans and Pseudomonas putida, regardless of mentholation status. However, further comparative analysis of the five products revealed significant differences in the bacterial compositions across products. Bacterial community richness was higher among non-mentholated products compared to those that were mentholated, particularly those that were custom-mentholated. In addition, mentholation appeared to be correlated with a reduction in potential human bacterial pathogens and an increase in bacterial species resistant to harsh environmental conditions. Taken together, these data provide preliminary evidence that the mentholation of commercially available cigarettes can impact the bacterial community of these products.Item Methylome Analysis in Chickens Immunized with Infectious Laryngotracheitis Vaccine(PLOS (Public Library of Science), 2015-06-24) Carrillo, José A.; He, Yanghua; Luo, Juan; Menendez, Kimberly R.; Tablante, Nathaniel L.; Zhao, Keji; Paulson, Joseph N.; Li, Bichun; Song, JiuzhouIn this study we investigated the methylome of chickens immunized with Infectious laryngotracheitis (ILT) vaccine derived from chicken embryos. Methyl-CpG binding domain proteinenriched genome sequencing (MBD-Seq) method was employed in the detection of the 1,155 differentially methylated regions (DMRs) across the entire genome. After validation, we ascertained the genomic DMRs distribution and annotated them regarding genes, transcription start sites (TSS) and CpG islands. We found that global DNA methylation decreased in vaccinated birds, presenting 704 hypomethylated and 451 hypermethylated DMRs, respectively. Additionally, we performed an enrichment analysis detecting gene networks, in which cancer and RNA post-transcriptional modification appeared in the first place, followed by humoral immune response, immunological disease and inflammatory disease. The top four identified canonical pathways were EIF2 signaling, regulation of EIF4 and p70S6K signaling, axonal guidance signaling and mTOR signaling, providing new insight regarding the mechanisms of ILT etiology. Lastly, the association between DNA methylation and differentially expressed genes was examined, and detected negative correlation in seventeen of the eighteen genes.