Browsing by Subject "Actinobacteria"

Now showing 1 - 5 of 5
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    Acute Administration of the Nonpathogenic, Saprophytic Bacterium, Mycobacterium vaccae, Induces Activation of Serotonergic Neurons in the Dorsal Raphe Nucleus and Antidepressant-Like Behavior in Association with Mild Hypothermia
    (Springer, 2018) Siebler, Philip H.; Heinze, Jared D.; Kienzle, Drake M.; Hale, Matthew W.; Lukkes, Jodi L.; Donner, Nina C.; Kopelman, Jared M.; Rodriguez, Orlando A.; Lowry, Christopher A.; Psychiatry, School of Medicine
    Peripheral immune activation can have profound physiologic and behavioral effects. One mechanism through which immune activation may affect physiology and behavior is through actions on brainstem neuromodulatory systems, such as serotonergic systems. To test this hypothesis, in Experiment 1, adult male BALB/c mice were implanted with telemetric recording devices and then immunized with Mycobacterium vaccae NCTC 11659 (0.1 mg, s.c.; Days - 28, - 14; N = 36). On Day 1, mice received an acute challenge with M. vaccae (0.1 mg, s.c.) or borate-buffered saline vehicle. Core body temperature and locomotor activity recordings were conducted during a 36 h period beginning 24 h prior to challenge; 12 h following acute challenge, mice were either tested in a 6-min forced swim test, or served as home cage controls (n = 9 per group). In Experiment 2, the protocol was repeated, but with the aim of assessing c-Fos expression in brainstem serotonergic neurons, assessed 90 min following exposure to forced swim (N = 32; n = 8 per group). In Experiment 1, acute M. vaccae challenge in M. vaccae-immunized mice, relative to vehicle-challenged controls, decreased locomotor activity and core body temperature measured 3 h following challenge, as measured by continuous telemetric recordings, and decreased immobility in the forced swim test measured 12 h following challenge. In Experiment 2, acute M. vaccae challenge in M. vaccae-immunized mice decreased home cage locomotion, in alignment with findings in Experiment 1, as measured by video-based behavioral analysis, and, among mice exposed to the forced swim test, increased c-Fos expression in subsets of serotonergic neurons within the dorsal raphe nucleus (DR) measured 13.5 h following challenge. Together, these data are consistent with the hypothesis that acute peripheral immune activation with a heat-killed preparation of M. vaccae transiently induces mild hypothermia in association with suppression of locomotor activity, activates subsets of serotonergic neurons in the DR, and induces antidepressant-like behavioral responses.
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    Disulfide bonds are required for cell division, cell envelope biogenesis and antibiotic resistance proteins in mycobacteria
    (bioRxiv, 2025-01-28) Mejia-Santana, Adrian; Collins, Rebecca; Doud, Emma H.; Landeta, Cristina; Biochemistry and Molecular Biology, School of Medicine
    Mycobacteria, including Mycobacterium tuberculosis-the etiological agent of tuberculosis-have a unique cell envelope critical for their survival and resistance. The cell envelope's assembly and maintenance influence permeability, making it a key target against multidrug-resistant strains. Disulfide bond (DSB) formation is crucial for the folding of cell envelope proteins. The DSB pathway in mycobacteria includes two enzymes, DsbA and VKOR, required for survival. Using bioinformatics and cysteine profiling proteomics, we identified cell envelope proteins dependent on DSBs. We validated via in vivo alkylation that key proteins like LamA (MmpS3), PstP, LpqW, and EmbB rely on DSBs for stability. Furthermore, chemical inhibition of VKOR results in phenotypes similar to those of Δvkor. Thus, targeting DsbA-VKOR systems could compromise both cell division and mycomembrane integrity. These findings emphasize the potential of DSB inhibition as a novel strategy to combat mycobacterial infections.
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    Montmorency Tart Cherry Supplementation Has Modest Effects on the Gut Microbiome and Markers of Gut Integrity and Insulin Resistance in Mice Fed Western Diet
    (Elsevier, 2021) Kaur, Amritpal; Ojo, Babajide; Wong, Siau Yen; Alake, Sanmi; Davila-El Rassi, Guadalupe; Pastor, Madison; Lin, Dingbo; Smith, Brenda; Lucas, Edralin; Obstetrics and Gynecology, School of Medicine
    Objectives: This study investigated the dose-dependent effects of freeze-dried Montmorency tart cherry (TC) supplementation on gut health and metabolic parameters in mice fed a western diet (WD). Methods: Six-week-old male C57BL/6 mice were randomly assigned to dietary treatment groups in a 2 × 3 factorial design with diet (control [AIN-93M] or WD, 45% fat kcal and 26% sucrose kcal) and TC (0, 5, 10% wt/wt) as factors for 12 wks. At the end of dietary treatment, body composition was assessed by dual energy xray absorptiometry, and tissues were collected to evaluate metabolic parameters and markers of gut health. Cecal content was used for bacterial and short chain fatty acid analyses (SCFAs). Results: TC at the 10% dose significantly increased the abundance of the beneficial bacterial phylum, Actinobacteria, relative to the unsupplemented groups (P = 0.018 and 0.010 vs control and WD, respectively). Relative cecal weight (P = 0.007) and SCFAs were significantly increased (P < 0.05) with TC supplementation (∼20% and 2-fold for relative cecal weight and SCFAs, respectively). Histological evaluation revealed reduced ileal villi height (P = 0.0348), width (P = 0.0042) and area (P = 0.0132) with WD, and TC did not alter this response. Overall, the expression of genes related to gut health (i.e barrier integrity marker, mucus layer formation, and inflammatory marker), were unaffected by both WD and TC supplementation. Body weight (P = 0.0012), fat mass (P = 0.007), fasting blood glucose (P = 0.001), serum total cholesterol (P < 0.0001), triglyceride (P = 0.002), leptin (P = 0.0011), plasminogen activator inhibitor 1 (P = 0.0344), and resistin (P = 0.0012) were increased with WD, and TC had no effect on these parameters. Despite modest effects on metabolic parameters, the homeostatic model assessment of insulin resistance, HOMA-IR, a commonly used tool for assessing insulin resistance, was improved by 50% with the 5% TC (P = 0.0003). Conclusions: TC supplementation restored some beneficial bacteria and increased SCFAs altered by WD. However, these changes in the gut did not translate to improvement in metabolic outcomes except for HOMA-IR. The mechanism by which TC improves HOMA-IR needs to be investigated in future studies.
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    Origin and Fate of Odorous Metabolites, 2-Methylisoborneol and Geosmin, in a Eutrophic Reservoir
    (2019-06) Clercin, Nicolas André; Druschel, Gregory K.; Jacinthe, Pierre-André; Filippelli, Gabriel; Moreno-Madriñán, Max Jacobo; Janga, Sarath Chandra
    Taste-and-Odor (T&O) occurrences are a worldwide problem and can locally have extensive socio-economic impacts in contaminated waterbodies. Tracing odorous compounds in surface waters or controlling the growth of producing organisms is particularly challenging. These approaches require the understanding of complex interactions between broad climate heterogeneity, large-scale physical processes such basin hydrology, lake/reservoir circulation, responses of aquatic ecosystems and communities. Eagle Creek Reservoir (ECR), a eutrophic water body, located in central Indiana experiences annual odorous outbreaks of variable durations and intensities that can impair its water quality. Two major compounds, 2-methylisoborneol and geosmin, have been identified as the main culprits occurring seasonally when the reservoir receives high discharges and nutrient loads from its main tributaries. Under these conditions, the growth of T&O-producing bacteria tends to take over other phytoplanktic organisms. Discrete samples collected within the water column during severe outbreaks in 2013 revealed that some bacterioplankton members belonging to Actinobacteria (Streptomyces) and Cyanobacteria (Planktothrix) were involved in the generation of T&O compounds. Most of this production occurred in the upper layers of the water column where higher abundances of key enzymes from MIB and geosmin metabolic pathways were detected. Application of a copper-based algaecide to curb the biosynthesis of bacterial metabolites led to geosmin production (linked to Cyanobacteria) being quickly terminated, whereas MIB levels (linked to Actinobacteria) lingered for several weeks after the algaecide treatment. Significant chemical differences in the association of these metabolites were measured in ECR. Geosmin was dominantly found cell-bound and settling after cellular death increases susceptibility to biodegradation in bottom sediments. MIB was mostly found dissolved making it less susceptible to biodegradation in bottom sediments. Genetic data identified Novosphingobium hassiacum and Sphingomonas oligophenolica (α- Proteobacteria) as potential degraders of geosmin and, four Flavobacterium species (Bacteroidetes) as potential MIB degraders. The role of Eagle Creek natural sediments in the removal of bacterial metabolites via chemical adsorption was also tested but was not proven efficient. Bacterial breakdown activity was demonstrated to be the major loss mechanism of MIB and geosmin.
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    Taste and Odor Event Dynamics of a Midwestern Freshwater Reservoir
    (2020-11) Howard, Chase Steven; Druschel, Gregory K.; Jacinthe, Pierre-André; Picard, Christine J.
    Eagle Creek Reservoir (ECR), located in the Midwestern U.S., is a freshwater limnic system plagued by seasonal Harmful Algal Blooms (HABs) which generate water-fouling Geosmin (GSM) and 2-Methylisoborneol (MIB) Taste and Odor (T&O) compounds. Past investigations of T&O event dynamics have identified Actinomycetes as responsible for MIB production and several genera of cyanobacteria for GSM production. During 2018, a temporally and spatially expansive sampling regimen of the reservoir was carried out and a battery of biological, chemical, physical, and hyperspectral experiments performed. The resulting data was analyzed using time series, cross-correlation, lag time, and multivariate analyses as well as machine learning algorithms to pick apart and interrogate any relationships between HABs, T&O events, and environmental parameters. The results show that local weather and watershed conditions exert significant control over the state of the reservoir and the behavior of the algal community. GSM and MIB peaked during early May under well-mixed, cold, and nutrient-rich water column conditions, then declined under summer thermal stratification before making a small resurgence during late season mixing. Bloom die-off and decay was effectively ruled out as a mechanism controlling T&O concentrations, and no links were found between T&O concentrations and algal biomass. Strong evidence was found that GSM/MIB concentrations were a response by bloom microbes to changing nutrient conditions within the reservoir, and it was determined that nutrient fluxes from the watershed 30-40 days prior to peak T&O concentrations are likely instrumental in the development of the slow- ix growing microbes characteristic of the reservoir. Attempts were made to assess spatial and temporal variability but no significant spatial differences were identified; differences between sampling sites were far smaller than differences between different sampling dates. The findings here add to the growing body of literature showing T&O and HAB dynamics are more closely linked to the relative abundance and speciation of nutrients than other parameters. Additionally, these findings carry important implications for the management of ECR and other similar freshwater reservoirs while highlighting the importance of reducing watershed eutrophication.