Browsing by Subject "microbiology"

Now showing 1 - 9 of 9
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    A phylogenetic transform enhances analysis of compositional microbiota data.
    (Elife, 2017-02-15) Silverman, Justin D; Washburne, Alex D; Mukherjee, Sayan; David, Lawrence A
    Surveys of microbial communities (microbiota), typically measured as relative abundance of species, have illustrated the importance of these communities in human health and disease. Yet, statistical artifacts commonly plague the analysis of relative abundance data. Here, we introduce the PhILR transform, which incorporates microbial evolutionary models with the isometric log-ratio transform to allow off-the-shelf statistical tools to be safely applied to microbiota surveys. We demonstrate that analyses of community-level structure can be applied to PhILR transformed data with performance on benchmarks rivaling or surpassing standard tools. Additionally, by decomposing distance in the PhILR transformed space, we identified neighboring clades that may have adapted to distinct human body sites. Decomposing variance revealed that covariation of bacterial clades within human body sites increases with phylogenetic relatedness. Together, these findings illustrate how the PhILR transform combines statistical and phylogenetic models to overcome compositional data challenges and enable evolutionary insights relevant to microbial communities.
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    Antibiotic-induced changes in the microbiota disrupt redox dynamics in the gut.
    (eLife, 2018-06-19) Reese, Aspen T; Cho, Eugenia H; Klitzman, Bruce; Nichols, Scott P; Wisniewski, Natalie A; Villa, Max M; Durand, Heather K; Jiang, Sharon; Midani, Firas S; Nimmagadda, Sai N; O'Connell, Thomas M; Wright, Justin P; Deshusses, Marc A; David, Lawrence A
    How host and microbial factors combine to structure gut microbial communities remains incompletely understood. Redox potential is an important environmental feature affected by both host and microbial actions. We assessed how antibiotics, which can impact host and microbial function, change redox state and how this contributes to post-antibiotic succession. We showed gut redox potential increased within hours of an antibiotic dose in mice. Host and microbial functioning changed under treatment, but shifts in redox potentials could be attributed specifically to bacterial suppression in a host-free ex vivo human gut microbiota model. Redox dynamics were linked to blooms of the bacterial family Enterobacteriaceae. Ecological succession to pre-treatment composition was associated with recovery of gut redox, but also required dispersal from unaffected gut communities. As bacterial competition for electron acceptors can be a key ecological factor structuring gut communities, these results support the potential for manipulating gut microbiota through managing bacterial respiration.
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    Epstein-Barr virus ensures B cell survival by uniquely modulating apoptosis at early and late times after infection.
    (Elife, 2017-04-20) Price, Alexander M; Dai, Joanne; Bazot, Quentin; Patel, Luv; Nikitin, Pavel A; Djavadian, Reza; Winter, Peter S; Salinas, Cristina A; Barry, Ashley Perkins; Wood, Kris C; Johannsen, Eric C; Letai, Anthony; Allday, Martin J; Luftig, Micah A
    Latent Epstein-Barr virus (EBV) infection is causally linked to several human cancers. EBV expresses viral oncogenes that promote cell growth and inhibit the apoptotic response to uncontrolled proliferation. The EBV oncoprotein LMP1 constitutively activates NFκB and is critical for survival of EBV-immortalized B cells. However, during early infection EBV induces rapid B cell proliferation with low levels of LMP1 and little apoptosis. Therefore, we sought to define the mechanism of survival in the absence of LMP1/NFκB early after infection. We used BH3 profiling to query mitochondrial regulation of apoptosis and defined a transition from uninfected B cells (BCL-2) to early-infected (MCL-1/BCL-2) and immortalized cells (BFL-1). This dynamic change in B cell survival mechanisms is unique to virus-infected cells and relies on regulation of MCL-1 mitochondrial localization and BFL-1 transcription by the viral EBNA3A protein. This study defines a new role for EBNA3A in the suppression of apoptosis with implications for EBV lymphomagenesis.
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    Frequency of Occult High-Grade Squamous Intraepithelial Neoplasia and Invasive Cancer within Anal Condylomata in Men Who Have Sex with Men
    (2010) Schlecht, Hans P; Fugelso, Dana K; Murphy, Ryan K; Wagner, Katiri T; Doweiko, John P; Proper, JoAnn; Dezube, Bruce J; Panther, Lori A
    Human papillomavirus causes anal condylomata, high-grade anal intraepithelial neoplasia, and anal squamous cell cancer. We found high-grade intraepithelial neoplasia or squamous cell cancer in 75 (47%) of 159 HIV-seropositive men who have sex with men (MSM) and in 42 (26%) of 160 HIV-seronegative MSM with anal condylomata meriting surgery (P < .001, determined by use of the X-2 test). Anal condylomata in MSM often harbor high-grade intraepithelial neoplasia and squamous cell cancer.
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    Global Trends in Typhoid and Paratyphoid Fever
    (2010) Crump, John A; Mintz, Eric D
    Typhoid and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and Southeast Asia, where enteric fever is associated with poor sanitation and unsafe food and water. High-quality incidence data from Asia are underpinning efforts to expand access to typhoid vaccines. Efforts are underway to develop vaccines that are immunogenic in infants after a single dose and that can be produced locally in countries of endemicity. The growing importance of Salmonella enterica serotype Paratyphi A in Asia is concerning. Antimicrobial resistance has sequentially emerged to traditional first-line drugs, fluoroquinolones, and third-generation cephalosporins, posing patient treatment challenges. Azithromycin has proven to be an effective alternative for treatment of uncomplicated typhoid fever. The availability of full genome sequences for S. enterica serotype Typhi and S. enterica serotype Paratyphi A confirms their place as monomorphic, human-adapted pathogens vulnerable to control measures if international efforts can be redoubled.
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    Lessons Learned from the Anaerobe Survey: Historical Perspective and Review of the Most Recent Data (2005-2007)
    (2010) Snydman, David R; Jacobus, Nilda V; McDermott, Laura A; Golan, Yoav; Hecht, David W; Goldstein, Ellie JC; Harrell, Lizzie; Jenkins, Stephen; Newton, Duane; Pierson, Carl; Rihs, John D; Yu, Victor L; Venezia, Richard; Finegold, Sydney M; Rosenblatt, Jon E; Gorbach, Sherwood L
    Background. The rationale and lessons learned through the evolution of the National Survey for the Susceptibility of Bacteroides fragilis Group from its initiation in 1981 through 2007 are reviewed here. The survey was conceived in 1980 to track emerging antimicrobial resistance in Bacteroides species. Methods. Data from the last 11 years of the survey (1997-2007), including 6574 isolates from 13 medical centers, were analyzed for in vitro antimicrobial resistance to both frequently used and newly developed anti-anaerobic agents. The minimum inhibitory concentrations of the antibiotics were determined using agar dilution in accordance with Clinical and Laboratory Standards Institute recommendations. Results. The analyses revealed that the carbapenems (imipenem, meropenem, ertapenem, and doripenem) and piperacillin-tazobactam were the most active agents against these pathogens, with resistance rates of 0.9%-2.3%. In the most recent 3 years of the survey (2005-2007), resistance to some agents was shown to depend on the species, such as ampicillin-sulbactam against Bacteroides distasonis (20.6%) and tigecycline against Bacteroides uniformis and Bacteroides eggerthii (similar to 7%). Very high resistance rates (>50%) were noted for moxifloxacin and trovafloxacin, particularly against Bacteroides vulgatus. During that period of study, non-B. fragilis Bacteroides species had >40% resistance to clindamycin. Metronidazole-resistant Bacteroides strains were also first reported during that period. Conclusions. In summary, resistance to antibiotics was greater among non-B. fragilis Bacteroides species than among B. fragilis and was especially greater among species with a low frequency of isolation, such as Bacteroides caccae and B. uniformis. The emergence of resistance among the non-B. fragilis Bacteroides species underscores the need for speciation of B. fragilis group isolates and for clinicians to be aware of associations between species and drug resistance.
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    Perforin and IL-2 Upregulation Define Qualitative Differences among Highly Functional Virus-Specific Human CD8(+) T Cells
    (2010) Ferrari, Guido
    The prevailing paradigm of T lymphocyte control of viral replication is that the protective capacity of virus-specific CD8(+) T cells is directly proportional to the number of functions they can perform, with IL-2 production capacity considered critical. Having recently defined rapid perforin upregulation as a novel effector function of antigen-specific CD8(+) T cells, here we sought to determine whether new perforin production is a component of polyfunctional CD8(+) T cell responses that contributes to the control of several human viral infections: cytomegalovirus (CMV), Epstein-Barr virus (EBV), influenza (flu), and adenovirus (Ad). We stimulated normal human donor PBMC with synthetic peptides whose amino acid sequences correspond to defined CTL epitopes in the aforementioned viruses, and then used polychromatic flow cytometry to measure the functional capacity and the phenotype of the responding CD8(+) T cells. While EBV and flu-specific CD8(+) T cells rarely upregulate perforin, CMV-specific cells often do and Ad stimulates an exceptionally strong perforin response. The differential propensity of CD8(+) T cells to produce either IL-2 or perforin is in part related to levels of CD28 and the transcription factor T-bet, as CD8(+) T cells that rapidly upregulate perforin harbor high levels of T-bet and those producing IL-2 express high amounts of CD28. Thus, "polyfunctional'' profiling of antigen-specific CD8(+) T cells must not be limited to simply the number of functions the cell can perform, or one particular memory phenotype, but should actually define which combinations of memory markers and functions are relevant in each pathogenic context.
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    Synergistic Pandemics: Confronting the Global HIV and Tuberculosis Epidemics
    (2010) Mayer, Kenneth H; Dukes Hamilton, Carol
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    The tricarboxylic acid cycle in Shewanella oneidensis is independent of Fur and RyhB control
    (2010) Yang, Yunfeng; McCue, Lee Ann; Parsons, Andrea B; Feng, Sheng; Zhou, Jizhong
    Background: It is well established in E. coli and Vibrio cholerae that strains harboring mutations in the ferric uptake regulator gene (fur) are unable to utilize tricarboxylic acid (TCA) compounds, due to the down-regulation of key TCA cycle enzymes, such as AcnA and SdhABCD. This down-regulation is mediated by a Fur-regulated small regulatory RNA named RyhB. It is unclear in the gamma proteobacterium S. oneidensis whether TCA is also regulated by Fur and RyhB. Results: In the present study, we showed that a fur deletion mutant of S. oneidensis could utilize TCA compounds. Consistently, expression of the TCA cycle genes acnA and sdhA was not down-regulated in the mutant. To explore this observation further, we identified a ryhB gene in Shewanella species and experimentally demonstrated the gene expression. Further experiments suggested that RyhB was up-regulated in fur mutant, but that AcnA and SdhA were not controlled by RyhB. Conclusions: These cumulative results delineate an important difference of the Fur-RyhB regulatory cycle between S. oneidensis and other gamma-proteobacteria. This work represents a step forward for understanding the unique regulation in S. oneidensis.