Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “microbial function”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,297 records · Page 72Linked to original sources
PubMed1981

Biochemical stratagem for obligate parasitism of eukaryotic cells by Coxiella burnetii.

Coxiella burnetti, the etiologic agent of Q fever, is an oligate intracellular parasite of eukaryotes. Unlike the majority of successful bacterial parasites, which escape the bactericidal environment of the phagolysosome by various means, C. burnetii multiplies only in the phagolysosome. In view of the relatively harsh environment inhabited by C. burnetii, we have examined (i) the in vitro metabolism of glucose and glutamate by whole cells of C. burnetii under conditions designed to approximate the pH within the phagolysosome and (ii) the effect of manipulation of the phagolysosomal pH by lysosomotropic amines on the replication of C. burnetii in chicken embryo fibroblasts. The transport, catabolism, and incorporation of both glucose and glutamate were found to be highly stimulated by acidic conditions, whereas at pH 7.0 metabolism of these substrates was minimal. The transport processes were shown to be energy dependent and highly sensitive to inhibition by uncouplers of oxidative phosphorylation. Increasing the phagolysosomal pH of infected chicken embryo fibroblasts by use of the lysosomotropic agents chloroquine, methylamine, or ammonium chloride inhibited the multiplication of C. burnetii, thus demonstrating the in vivo requirement for the acidic conditions of the phagolysosome. This apparent dependence upon phagosome--lysosome fusion to generate pH conditions favorable to C. burnetii replication suggests a unique biochemical mechanism of parasite activation. A pathogenic mechanism based on regulation of microbial metabolism by H+-dependent stimulation of cell function is proposed.

Animals↗
PubMed1993

Dietary fiber, inulin, and oligofructose: a review comparing their physiological effects.

Dietary fiber is a general term. It covers a wide variety of substances that belong to the family of carbohydrates that resist hydrolysis by human alimentary enzymes but are fermented by colonic microflora. The main physiological effects of dietary fiber are primarily on gastric emptying and small intestinal transit time, resulting in an improved glucose tolerance and a decreased digestion of starch: second, on colonic transit time and large bowel functions due to fermentation by ceco-colonic microbial flora or bulking action. The so-called soluble dietary fibers are fermented to a large extent by a wide variety of anaerobic bacteria that result in an increase in bacterial biomass, an increase in fecal mass, a change in intracolonic pH, and production of short chain fatty acids and various gases as metabolic end products. The insoluble fibers are only marginally fermented: they serve almost exclusively as bulking agents that result in shorter transit time and increased fecal mass. The short chain fatty acids resulting from the colonic fermentation of dietary fiber are largely absorbed via the portal blood and reach both the liver and the peripheral tissues. They induce changes in glucose and fat metabolism leading to post-prandial hypoglycemia and long-term hypolipidemia. Inulin and oligofructose are fructans with a degree of polymerization of 2 to 60 and 2 to 20, respectively. Due to the structural conformation of their osidic bridge (beta 2-1), they both resist the hydrolysis by human alimentary enzymes. Moreover, when reaching the colon, both inulin and oligofructose are almost quantitatively fermented almost exclusively by colonic bifidobacteria and bacteroides. Such an extensive fermentation causes an increase in fecal bacterial biomass, a decrease in ceco-colonic pH, and produces a large amount of fermentation products among which the short chain fatty acids that exert systemic effects on lipid metabolism. Thus, both inulin and oligofructose have most of the characteristics of a dietary fiber and the proposal is made to classify them as such. Moreover, they are bifidogenic factors, because, due to still unknown reasons, they are primarily fermented by bifidobacteria. It is concluded from this review that "nondigestible fructo-oligosaccharides," even though they are not included in the carbohydrate fraction that is quantified as dietary fiber by classic analytical methods, have most of the physiological effects of a dietary fiber.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2004

Expression of HLA-G in inflammatory bowel disease provides a potential way to distinguish between ulcerative colitis and Crohn's disease.

In addition to being involved in nutrient uptake, the epithelial mucosa constitute the first line of defense against microbial pathogens. A direct consequence of this physiological function is a very complex network of immunological interactions that lead to a strong control of the mucosal immune balance. The dysfunction of immunological tolerance is likely to be a cause of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD). HLA-G is a non-classical major histocompatibility complex (HLA) class I molecule, which is highly expressed by human cytotrophoblast cells. These cells play a role in immune tolerance by protecting trophoblasts from being killed by uterine NK cells. Because of the deregulation of immune system activity in IBD, as well as the immunoregulatory role of HLA-G, we have analyzed the expression of HLA-G in intestinal biopsies of patients with UC and CD. Our study shows that the differential expression of HLA-G provides a potential way to distinguish between UC and CD. Although the reason for this differential expression is unclear, it might involve a different mechanism of immune regulation. In addition, we demonstrate that in the lamina propria of the colon of patients with UC, IL-10 is strongly expressed. In conclusion, the presence of HLA-G on the surface of intestinal epithelial cell in patients with UC lends support to the notion that this molecule may serve as a regulator of mucosal immune responses to antigens of undefined origin. Thus, this different pattern of HLA-G expression may help to differentiate between the immunopathogenesis of CD and UC.

Biopsy↗
PubMed2026

Boreal and subarctic freshwaters harbour a diversity of jumbophages.

Bacteriophages (phages) are major drivers of microbial evolution and ecology, yet their diversity and functional roles remain poorly characterized in many natural environments, such as in freshwater systems. In boreal and subarctic freshwater habitats, where bacteria are typically slow-growing and nutrient-limited, phages are predicted to have a critical role in host regulation and horizontal gene exchange. However, only a few isolates have been obtained from such environments, leaving the genetic and functional diversity of these phages largely unexplored. Here, we present a collection of 40 bacteriophages isolated from boreal lakes and rivers using a set of diverse freshwater bacterial hosts. Despite using conventional isolation methods, eight of the isolates possess genomes larger than 200 kilobases and are classified as jumbophages. All jumbophages exhibited myovirus morphology and comparatively slow infection dynamics. These jumbophages include the first known representatives infecting members of Janthinobacterium and Herbaspirillum. Comparative genomic and phylogenetic analyses show that nearly all genomes are distinct from previously described phages, indicating substantial novelty. Diverse auxiliary metabolic and anti-defence systems were identified, including putative NAD+ salvage and acyl carrier protein modules, along with predicted Anti-Thoeris and Anti-CBASS elements. The Pseudomonas-infecting jumbophage Ahti encoded homologues of all 21 core genes that define the nucleus-forming family Chimalliviridae. Additionally, Ahti displayed compartmentalization of DNA during infection, establishing it as the first freshwater nucleus-forming phage. These findings expand our understanding of the ecological, genomic, and functional diversity of phages in boreal environments and highlight the role of freshwater ecosystems as significant reservoirs of novel viral lineages.

anti-defence systems↗
PubMed1975

Immunologic reconstitution in man--present status.

Recent advances in immunobiology have shed new light on our understanding of the essential role of immunity as it relates to body economy. Immunity, once thought to be the primary defense mechanism against microbial infection, appears to have a much broader function--recognition and elimination of foreign bodies and preservation of the integrity of the individual. As our understanding of the pathophysiology of the immune system became more clear, immunologic reconstitution emerged as a new, promising mode of treatment for a variety of diseases with immunodeficiency. Bone marrow transplantation, thymus transplanation, transfer factor therapy, infusion of leukocytes, BCG vaccination, and other specific or nonspecific immunostimulants have been tried, with dramatic beneficial results in some instances. Although still in its infant stage, this form of treatment appears to have great potential and wide application in the prevention and treatment, not only of primary immunodeficiency, but also of many other diseases such as cancer, the so-called autoimmune diseases, and even aging.

Animals↗
PubMed2006

Versatility of pneumococcal surface proteins.

Surface-exposed proteins are key players during the infectious process of pathogenic bacteria. The cell surface of the Gram-positive human pathogen Streptococcus pneumoniae is decorated not only by typical Gram-positive surface proteins, but also by a family of proteins that recognizes the phosphorylcholine of the lipoteichoic and teichoic acids, namely the choline-binding proteins, and by non-classical surface proteins that lack a leader peptide and membrane-anchor motif. A comprehensive understanding of how microbial proteins subvert host immunity or host protein functions is a prerequisite for the development of novel therapeutic strategies to combat pneumococcal infections. This article reviews recent progress in the investigation of the versatility and sophistication of the virulence functions of surface-exposed pneumococcal proteins.

Bacterial Outer Membrane Proteins↗
PubMed1988

Utilization of microbial siderophores in iron acquisition by oat.

Iron uptake by oat (Avena sativa cv Victory) was examined under hydroponic chemical conditions that required direct utilization of microbial siderophores for iron transport. Measurements of iron uptake rates by excised roots from the hydroxamate siderophores, ferrichrome, ferrichrome A, coprogen, ferrioxamine B (FOB), and rhodotorulic acid (RA) showed all five of the siderophores supplied iron, but that FOB and RA were preferentially utilized. FOB-mediated iron uptake increased four-fold when roots were preconditioned to iron stress and involved an active, iron-stress induced transport system that was inhibited by 5 millimolar sodium azide or 0.5 millimolar dinitrophenol. Kinetic studies indicated partial saturation with an apparent K(m) of 5 micromolar when FOB was supplied at 0.1 to 50 micromolar concentrations. Whole plant experiments confirmed that 5 micromolar FOB was sufficient for plant growth. Siderophore-mediated iron transport was inhibited by Cr-ferrichrome, an analog of ferrated siderophore. Our results confirm the existence of a microbial siderophore iron transport system in oat which functions within the physiological concentrations produced and used by soil microorganisms.

Journal Article↗
PubMed2007

Microarray-based analysis of changes in diversity of microbial genes involved in organic carbon decomposition following land use/cover changes.

To increase our understanding of the impact of land use/cover changes on soil microbial decomposition genes involved in organic carbon decomposition, we analyzed soil samples in four sites with different land cover/use histories in a subalpine region of western Sichuan. One site was in a primitive Abies faxoniana forest, the second and the third sites were spruce plantations established in 1960's and 1980's, respectively, and the fourth site was in a cropland dating back to 1960's. The genomic DNA from the microbial community was isolated and hybridized against a functional gene microarray containing 1,961 probes. There were 39, 62, 41, and 28 gene probes with statistically significant positive signals and the gene diversity index (H') values were 3.59, 4.04, 3.70 and 3.16 in primitive forest, spruce plantations established in 1960s and 1980s and cropland, respectively. The results suggested that the number of functional genes and the gene diversity index were correlated with increasing amounts of soil organic carbon, except in the primitive Abies faxoniana forest site. cluster analysis demonstrated that primitive forest soil was clustered more closely to soil from the spruce plantation established in 1960s.

Biodiversity↗
PubMed1999

Accumulation of 3-ketosteroids induced by itraconazole in azole-resistant clinical Candida albicans isolates.

The effects of itraconazole on ergosterol biosynthesis were investigated in a series of 16 matched clinical Candida albicans isolates which had been previously analyzed for mechanisms of resistance to azoles (D. Sanglard, K. Kuchler, F. Ischer, J. L. Pagani, M. Monod, and J. Bille, Antimicrob. Agents Chemother., 39:2378-2386, 1995). Under control conditions, all isolates contained ergosterol as the predominant sterol, except two strains (C48 and C56). In isolates C48 and C56, both less susceptible to azoles than their parent, C43, substantial concentrations (20 to 30%) of 14alpha-methyl-ergosta-8,24(28)-diene-3beta,6alpha-dio l (3, 6-diol) were found. Itraconazole treatment of C43 resulted in a dose-dependent inhibition of ergosterol biosynthesis (50% inhibitory concentration, 2 nM) and accumulation of 3,6-diol (up to 60% of the total sterols) together with eburicol, lanosterol, obtusifoliol, 14alpha-methyl-ergosta-5,7,22,24(28)-tetraene-3betaol, and 14alpha-methyl-fecosterol. In strains C48 and C56, no further increase of 3,6-diol was observed after exposure to itraconazole. Ergosterol synthesis was less sensitive to itraconazole inhibition, as was expected for these azole-resistant isolates which overexpress ATP-binding cassette transporter genes CDR1 and CDR2. In addition to 3,6-diol, substantial amounts of obtusifolione were found after exposure to itraconazole. This toxic 3-ketosteroid was demonstrated previously to accumulate after itraconazole treatment in Cryptococcus neoformans and Histoplasma capsulatum but has not been reported in Candida isolates. Accumulation of obtusifolione correlated with nearly complete growth inhibition in these azole-resistant strains compared to that found in the susceptible parent strain, although the onset of growth inhibition only occurred at higher concentrations of itraconazole. ERG25 and ERG26 are the only genes assigned to the 4-demethylation process, of which the 3-ketoreductase is part. To verify whether mutations in these ERG25 genes contributed to obtusifolione accumulation, their nucleotide sequences were determined in all three related isolates. No mutations in ERG25 alleles of isolates C48 and C56 were found, suggesting that this gene is not involved in obtusifolione accumulation. The molecular basis for the accumulation of this sterol in these two strains remains to be established.

Antifungal Agents↗
PubMed1993

Polymerase chain reaction amplification of naphthalene-catabolic and 16S rRNA gene sequences from indigenous sediment bacteria.

We report the amplification of bacterial genes from uninoculated surface and subsurface sediments by the polymerase chain reaction (PCR). PCR amplification of indigenous bacterial 16S ribosomal DNA genes was unsuccessful when subsurface sediment containing approximately 10(7) cells.g-1 was added directly to a PCR mixture. However, when 10 mg of sediment was inoculated with approximately 10(5) cells of Pseudomonas putida G7, the nahAc naphthalene dioxygenase gene characteristic of the P. putida G7 NAH7 plasmid was detected by PCR amplification. Southern blotting of the PCR amplification product improved sensitivity to 10(3) to 10(4) cells from samples inoculated with P. putida G7, but controls with no sediment added showed that the PCR was partially inhibited by the sediments. Lysozyme-sodium dodecyl sulfate-freeze-thaw DNA extraction was combined with gel electrophoretic partial purification in the presence of polyvinylpyrrolidone to render DNA from indigenous bacteria in surface or subsurface sediment samples amplifiable by PCR using eubacterial 16S ribosomal DNA primers. The nahAc gene could also be amplified from indigenous bacteria by using nahAc-specific primers when PCR conditions were modified by increasing Taq and primer concentrations. Restriction digests of the nahAc amplification products from surface and subsurface sediments revealed polymorphism relative to P. putida G7. The procedures for DNA extraction, purification, and PCR amplification described here demonstrate that the PCR is a potentially useful tool in studies of function- and taxon-specific DNA from indigenous microbial communities in sediment and groundwater environments.

Base Sequence↗
PubMed2006

arsRBOCT arsenic resistance system encoded by linear plasmid pHZ227 in Streptomyces sp. strain FR-008.

In the arsenic resistance gene cluster from the large linear plasmid pHZ227, two novel genes, arsO (for a putative flavin-binding monooxygenase) and arsT (for a putative thioredoxin reductase), were coactivated and cotranscribed with arsR1-arsB and arsC, respectively. Deletion of the ars gene cluster on pHZ227 in Streptomyces sp. strain FR-008 resulted in sensitivity to arsenic, and heterologous expression of the ars gene cluster in the arsenic-sensitive Streptomyces strains conferred resistance on the new hosts. The pHZ227 ArsB protein showed homology to the yeast arsenite transporter Acr3p. The pHZ227 ArsC appears to be a bacterial thioredoxin-dependent ArsC-type arsenate reductase with four conserved cysteine thioredoxin-requiring motifs.

Arsenic↗
PubMed1980

Effect of adult thymectomy on the development of 1-chloro-2,4-dinitrobenzene contact sensitivity and other T lymphocyte functions in patients with myasthenia gravis.

1-Chloro-2,4-dinitrobenzene (DNCB) contact sensitivity and other T lymphocyte functions were studied in thymectomized and non-thymectomized patients with myasthenia gravis. The ability to develop contact sensitivity was reduced in patients with myasthenia gravis and was further reduced after thymectomy. Memory lymphocyte function, as measured by skin tests with common microbial antigens, was intact. A positive phytohemagglutinin (PHA) skin test was found mainly in those patients who also developed contact sensitivity to DNCB. The number of rosette-forming T cells in the peripheral blood as well as mitogen stimulation with PHA was found to be normal in thymectomized as well as non-thymectomized patients. In the thymectomized group, mitogen stimulation with concanavalin A and staphylococcal protein A was also within the normal range, while increased stimulation was obtained with pokeweed mitogen (PWM) and purified protein derivative (PPD). No alteration in mixed lymphocyte culture reactivity or immunoglobulin levels was obtained compared with healthy blood donors. On the basis of these results, it is concluded that non-thymectomized as well as thymectomized patients with myasthenia gravis may have a defective subpopulation of T cells possibly residing in the TH1-positive population. Furthermore, the increased lymphocyte stimulation obtained with PPD and PWM may indicate a reduction of suppressor cell activity after thymectomy.

Adolescent↗
PubMed1989

Inhibition of endotoxin-induced bacterial translocation in mice.

The primary functions of the gut are to absorb nutrients and exclude bacteria and their products. However, under certain circumstances the gut may lose its barrier function and serve as a reservoir for systemic microbial infections. These experiments were performed to determine the mechanisms whereby endotoxin causes bacteria to escape (translocate) from the gut. Bacteria translocated from the gut to the mesenteric lymph nodes of mice challenged with nonlethal doses of Escherichia coli 026:B6 or E. coli 0111:B4 endotoxin. Physical disruption of the gut mucosal barrier appears to be the primary mechanism whereby endotoxin promotes bacterial translocation. Mucosal injury and endotoxin-induced bacterial translocation were reduced by inhibition (allopurinol) or inactivation (tung-sten diet) of xanthine oxidase activity (P less than 0.01), but were not affected by the platelet-activation factor antagonists, SRI 63-441 or BN 52021. Because the inhibition or inactivation of xanthine oxidase activity reduced both the extent of mucosal injury and endotoxin-induced bacterial translocation, the effect of endotoxin on the gut appears to be mediated, at least to some degree, by xanthine oxidase-generated, oxygen-free radicals.

Allopurinol↗
PubMed2001

Cost-effective whole-cell assay for laboratory evolution of hydroxylases in Escherichia coli.

Cytochrome P450 BM-3 from Bacillus megaterium catalyzes the subterminal hydroxylation of medium- and longchain fatty acids at the omega-1, omega-2, and omega-3 positions. A continuous spectrophotometric assay for P450 BM-3 based on the conversion of p-nitrophenoxycarboxylic acids (pNCA) to omega-oxycarboxylic acids and the chromophore p-nitrophenolate was reported recently. However, this pNCA assay procedure contained steps that limited its application in high throughput screening, including expression of P450 BM-3 variant F87A in 4-ml cultures, centrifugation, resuspension of the cell pellet, and cell lysis. We have shown that permeabilization of the outer membrane of Escherichia coli DH5alpha with polymyxin B sulfate, EDTA, polyethylenimine, or sodium hexametaphosphate results in rapid conversion of 12-pNCA. A NADPH-generating system consisting of NADP(+), D/L-isocitric acid, and the D/L-isocitrate dehydrogenase of E. coli DH5alpha reduced the cofactor expense more than 10-fold. By avoiding cell lysis, resuspension, and centrifugation, the high throughput protocol allows screening of thousands of samples per day.

Automation↗
PubMed2000

Metabolic flux balance analysis and the in silico analysis of Escherichia coli K-12 gene deletions.

BACKGROUND: Genome sequencing and bioinformatics are producing detailed lists of the molecular components contained in many prokaryotic organisms. From this 'parts catalogue' of a microbial cell, in silico representations of integrated metabolic functions can be constructed and analyzed using flux balance analysis (FBA). FBA is particularly well-suited to study metabolic networks based on genomic, biochemical, and strain specific information. RESULTS: Herein, we have utilized FBA to interpret and analyze the metabolic capabilities of Escherichia coli. We have computationally mapped the metabolic capabilities of E. coli using FBA and examined the optimal utilization of the E. coli metabolic pathways as a function of environmental variables. We have used an in silico analysis to identify seven gene products of central metabolism (glycolysis, pentose phosphate pathway, TCA cycle, electron transport system) essential for aerobic growth of E. coli on glucose minimal media, and 15 gene products essential for anaerobic growth on glucose minimal media. The in silico tpi-, zwf, and pta- mutant strains were examined in more detail by mapping the capabilities of these in silico isogenic strains. CONCLUSIONS: We found that computational models of E. coli metabolism based on physicochemical constraints can be used to interpret mutant behavior. These in silica results lead to a further understanding of the complex genotype-phenotype relation.

Computational Biology↗
PubMed2006

The secretion of HMGB1 is required for the migration of maturing dendritic cells.

Chemokines regulate the migration and the maturation of dendritic cells (DC) licensed by microbial constituents. We have recently found that the function of DC, including their ability to activate naïve, allogeneic CD4+ T cells, requires the autocrine/paracrine release of the nuclear protein high mobility group box 1 (HMGB1). We show here that human myeloid DC, which rapidly secrete upon maturation induction their own HMGB1, remodel their actin-based cytoskeleton, up-regulate the CCR7 and the CXCR4 chemokine receptors, and acquire the ability to migrate in response to chemokine receptor ligands. The events are apparently causally related: DC challenged with LPS in the presence of HMGB1-specific antibodies fail to up-regulate the expression of the CCR7 and CXCR4 receptors and to rearrange actin-rich structures. Moreover, DC matured in the presence of anti-HMGB1 antibodies fail to migrate in response to the CCR7 ligand CCL19 and to the CXCR4 ligand CXCL12. The blockade of receptor for advanced glycation end products (RAGE), the best-characterized membrane receptor for HMGB1, impinges as well on the up-regulation of chemokine receptors and on responsiveness to CCL19 and CXCL12. Our data suggest that the autocrine/paracrine release of HMGB1 and the integrity of the HMGB1/RAGE pathway are required for the migratory function of DC.

Cells, Cultured↗
PubMed2004

Dietary modification of the intestinal microbiota.

Humans harbor a consortium of commensal bacteria in their gut that are thought to be crucial for normal health. However, the extent of microbial diversity in the gut and the physiologic functions of the microflora have not yet been fully characterized. Molecular tools are now available to characterize the associations between diet, microflora composition, and health in greater depth. New molecular studies have confirmed earlier culture-based observations that diet has a role in the regulation of microflora composition. In the near future, new insight into these associations should allow for the design of specific diets aimed at improving health by modulating microflora.

Animals↗