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PubMed2006

Pulmonary surfactant proteins A and D: innate immune functions and biomarkers for lung diseases.

Pulmonary surfactant, a complex of lipids and proteins, functions to keep alveoli from collapsing at expiration. Surfactant proteins A (SP-A) and D (SP-D) belong to the collectin family and play pivotal roles in the innate immunity of the lung. Pulmonary collectins directly bind with broad specificities to a variety of microorganism and possess anti-microbial effects. These proteins also exhibit both inflammatory and anti-inflammatory functions, which occur through interactions with pattern recognition receptors including Toll-like receptor and CD14, signal inhibitory regulatory protein alpha and a receptor complex of calreticulin and CD91. The collectins enhance phagocytosis of microbes by macrophages through opsonic and/or non-opsonic activities. The proteins stimulate cell surface expression of phagocytic receptors including scavenger receptor A and mannose receptor. Since the expression of SP-A and SP-D is abundant and restricted within the lung, the proteins are now clinically used as biomarkers for lung diseases. The levels of SP-A and SP-D in bronchoalveolar lavage fluids, amniotic fluids, tracheal aspirates and pleural effusions reflect alterations in alveolar compartments and epithelium, and lung maturity. The determination of SP-A and SP-D in sera is a non-invasive and useful tool for understanding some pathological changes of the lung in the diseases, including pulmonary fibrosis, collagen vascular diseases complicated with interstitial lung disease, pulmonary alveolar proteinosis, acute respiratory distress syndrome and radiation pneumonitis.

Animals↗
PubMed2026

Discovering hidden candidate plastic-degrading enzymes: Combined multi-omics and machine learning strategy.

Plastic pollution poses a major threat to the stability of natural ecosystems as well as human health. Microbial enzymes have long been considered a potential resource for targeted biodegradation but, except for a few successful cases, the discovery of efficient enzymes has proved challenging. Aiming to accelerate the process, we propose an approach combining metagenomics, metatranscriptomics and semi-supervised learning that selects promising plastic-degrading candidate enzymes from the proteome of relevant microorganisms. Tested on a dataset of over 10,000 microbial proteins, ranking models consistently prioritize known plastic-degrading enzymes, achieving an area under the cumulative distribution function curve above 0.96, with leave-one-family-out cross-validation indicating that performance is largely retained across protein families. As a case study, this work focuses on mixed microbial cultures exposed for extended periods to polyethylene, polyethylene terephthalate, and polyurethane substrates. The prevalent species after selective enrichment were functionally characterized, finding Rhodococcus aetherivorans as the most relevant species in two of the five cultures under investigation. Among the top-ranked proteins, several have high structural similarity with known enzymes despite not being identified by sequence similarity search. Moreover, according to metatranscriptomics results, several of these enzymes were found to be expressed at the same level or above that of annotated enzymes, suggesting that they may have functional relevance. Overall, this work highlights the potential of integrating multi-omics with data-driven methods for enzyme discovery and for accelerating the development of biotechnological solutions to plastic pollution.

Biodegradation, Environmental↗
PubMed2005

Host epithelial interactions with Helicobacter pylori: a role for disrupted gastric barrier function in the clinical outcome of infection?

Infection of the human stomach with Helicobacter pylori may develop into gastritis, ulceration, adenocarcinoma and mucosal lymphomas. The pathogenic mechanisms that determine the clinical outcome from this microbial-epithelial interaction remain poorly understood. An increasing number of reports suggests that disruptions of epithelial barrier function may contribute to pathology and postinfectious complications in a variety of gastrointestinal infections. The aim of this review is to critically discuss the implications of H pylori persistence on gastric disease, with emphasis on the role of myosin light chain kinase, claudins and matrix metalloproteinases in gastric permeability defects, and their contribution to the development of cancer. These mechanisms and the associated signalling events may represent novel therapeutic targets to control disease processes induced by H pylori, a microbial pathogen that colonizes the stomach of over 50% of the human population.

Cell Membrane Permeability↗
PubMed2002

Probiotics: on-going research on atopic individuals.

The challenge for the modern health care system is to fight against the increasing prevalence of atopic disease. The introduction of scientifically composed probiotic functional foods for prophylactic or therapeutic purposes could be one solution. Probiotics are live microbial food supplements or components of bacteria which have beneficial effects on human health. Specific strains have been demonstrated to exert powerful anti-pathogenic, anti-inflammatory and anti-allergic effects. The hygiene hypothesis suggests that atopic disease may arise from a lack of counterbalancing microbial exposure at an early age. The initial compositional development of the gut microflora is considered a key determinant of the development of both the immune responder phenotype and normal gut barrier functions. The regulatory role of probiotics in human allergic disease was first emphasised in the demonstration of a suppressive effect on lymphocyte proliferation and interleukin-4 generation in vitro. Subsequently, a significant improvement in the clinical course of atopic eczema was reported in infants given a probiotic-supplemented diet. The potential of probiotics to reduce the risk of atopic disease has recently been demonstrated in a double-blind, placebo-controlled study: probiotics administered pre- and postnatally for 6 months to at-risk subjects reduced the prevalence of atopic eczema to half of that observed in infants receiving placebo. Ongoing research is directed towards the development of novel techniques to characterise the gut microflora. Future research will clarify the mechanisms to control specific physiological processes in the evolution of atopic disease in at-risk populations or in the management of allergic diseases.

Diet↗
PubMedDate not supplied

Cutaneous photosynthesis of vitamin D: an evolutionary highly-conserved endocrine system that protects against environmental hazards including UV-radiation and microbial infections.

Phytoplankton and zooplankton have been producing vitamin D for more than 500 million years. While the function of vitamin D in the physiology of lower non-vertebrate organisms is not well understood, it is known that most vertebrates need vitamin D to develop and maintain a healthy mineralized skeleton. However, recent findings have demonstrated that 1,25(OH)2D, the biologically-active vitamin D metabolite, exerts a multitude of important physiological effects independently of the regulation of calcium and bone metabolism. These new functions of vitamin D include protection against cancer and other diseases in various tissues. In this review, current knowledge of an additional new function of the cutaneous photosynthesis of vitamin D, that has recently emerged, is summarized: the role of vitamin D as an evolutionary highly-conserved endocrine system that protects the skin and other tissues against environmental hazards, including ionizing and UV-radiation, microbial infections and oxidative stress, is discussed.

Endocrine System↗
PubMed2004

Platelets: signaling cells in the immune continuum.

Platelets have intricate signaling mechanisms and participate in a breadth of cellular interactions. This diversity is frequently unrecognized. In addition to being the chief cellular effectors of haemostasis, platelets are innate inflammatory cells that have previously unrecognized molecular pathways and synthetic capacities, which can link innate and adaptive responses in the immune continuum. Characterization of these features and parallel in vivo observations identify new sentinel, surveillance and information-transfer functions. Recent observations indicate that platelets have key roles in adaptive responses to microbial and antigen challenge, in addition to their well known acute defensive activities in tissue injury, and suggest that these mechanisms can be dysregulated in disease. Ongoing characterization of the platelet transcriptome, secretome and proteome also suggest that additional functions of platelets relevant to innate and adaptive immunity remain to be discovered. This Review is the third in a series on interactions between haemostasis and inflammation.

Animals↗
PubMed2005

The importance of Toll-like receptor 2 polymorphisms in severe infections.

Toll-like receptor 2 (TLR2) is a member of the TLR family, which plays a central role in the innate immune response to a wide variety of microorganisms. Animal studies have shown that TLR2-knockout mice are more susceptible to septicemia due to Staphylococcus aureus and Listeria monocytogenes, meningitis due to Streptococcus pneumoniae, and infection with Mycobacterium tuberculosis, suggesting that functional TLR2 polymorphisms may impair host response to a certain spectrum of microbial pathogens. In humans, 2 polymorphisms in the exon part of TLR2, which attenuate receptor signaling, enhance the risk of acute severe infections, tuberculosis, and leprosy. Because gram-positive bacteria have became the first cause of severe infections, including septic shock, knowledge of the role that alteration or lack of TLR2 function plays in the pathogenesis of infectious diseases could contribute to the design of new therapeutic strategies, including prevention, pharmacological intervention, and vaccine development.

Adaptor Proteins, Signal Transducing↗
PubMedDate not supplied

The synthesis and in vivo assembly of functional antibodies in yeast.

The yeast Saccharomyces cerevisiae can synthesize, process and secrete higher eukaryotic proteins. We have investigated the expression of immunoglobulin chains in yeast and demonstrate here the synthesis, processing and secretion of light and heavy chains, the glycosylation of heavy chain, the intracellular localization of these foreign proteins by immunofluorescence, and the detection of functional antibodies in cells co-expressing both chains. This may provide the basis of a microbial fermentation process for the production of monoclonal antibodies. The co-expression of light and heavy chains in Escherichia coli has been reported but functional antibodies were not assembled in vivo. Furthermore, only low-level assembly of these chains was found in vitro.

Antibodies, Fungal↗
PubMed2004

Bacterial diversity and function of aerobic granules engineered in a sequencing batch reactor for phenol degradation.

Aerobic granules are self-immobilized aggregates of microorganisms and represent a relatively new form of cell immobilization developed for biological wastewater treatment. In this study, both culture-based and culture-independent techniques were used to investigate the bacterial diversity and function in aerobic phenol- degrading granules cultivated in a sequencing batch reactor. Denaturing gradient gel electrophoresis (DGGE) analysis of PCR-amplified 16S rRNA genes demonstrated a major shift in the microbial community as the seed sludge developed into granules. Culture isolation and DGGE assays confirmed the dominance of beta-Proteobacteria and high-G+C gram-positive bacteria in the phenol-degrading aerobic granules. Of the 10 phenol-degrading bacterial strains isolated from the granules, strains PG-01, PG-02, and PG-08 possessed 16S rRNA gene sequences that matched the partial sequences of dominant bands in the DGGE fingerprint belonging to the aerobic granules. The numerical dominance of strain PG-01 was confirmed by isolation, DGGE, and in situ hybridization with a strain-specific probe, and key physiological traits possessed by PG-01 that allowed it to outcompete and dominate other microorganisms within the granules were then identified. This strain could be regarded as a functionally dominant strain and may have contributed significantly to phenol degradation in the granules. On the other hand, strain PG-08 had low specific growth rate and low phenol degradation ability but showed a high propensity to autoaggregate. By analyzing the roles played by these two isolates within the aerobic granules, a functional model of the microbial community within the aerobic granules was proposed. This model has important implications for rationalizing the engineering of ecological systems.

Aerobiosis↗
PubMed1995

The microbial flora associated with stable endosseous implants.

Eleven patients with 36 stable endosseous implants in function for at least six months were selected for culturing in this study. Each patient had been restored with a mandibular implant-borne bar overdenture. The bacterial samples were taken from the superior aspect of the implants after bar and abutment removal. The plaque specimens contained predominantly Gram-positive microflora, although Gram-negative species were present in low numbers. This study serves to corroborate previously published reports regarding the characterization of the microflora associated with stable endosseous implants.

Actinomyces↗
PubMed1999

The fermentable fiber content of the diet alters the function and composition of canine gut associated lymphoid tissue.

The ingestion of plant fibers and their susceptibility to microbial fermentation in the large bowel modulate intestinal morphology but little is known about effects on the gut associated lymphoid tissue (GALT). The aim of the present study was to determine the effect of consuming diets containing different levels of fermentability fiber on immune function. Sixteen adult mongrel dogs (23 +/- 2 kg) were fed (14 days) in a randomized cross over design two isoenergetic isonitrogenous diets containing 8.3 g/kg non-fermentable or 8.7 g/kg fermentable fibers. Lymphocytes were isolated from blood prior to starting the study and at the end of each diet period. At study completion, lymphocytes were isolated from the gut associated lymphoid tissue (GALT) of the small intestine for characterization by immunofluorescence and to determine their ability to respond to mitogenic stimulation. Feeding high fermentable fibers increased (P < 0.05) the CD4/CD8 ratio and decreased (P < 0.05) the proportion of B cells in peripheral blood without changing natural killer cell activity or the response to mitogens. Mesenteric lymph node cells from dogs fed the low then high fermentable fiber diet contained a higher (P < 0.05) proportion of CD4+ cells and a higher (P < 0.05) response to mitogens. Intraepithelial, Peyer's patches and lamina propria cells contained a greater (P < 0.05) proportion of CD8+ cells when dogs were fed a low fermentable fiber diet followed by a high fermentable fiber diet. T cell mitogen responses in vitro were higher for intraepithelial but lower for Peyer's patches and lamina propria cells from dogs who were fed the low fermentable fiber diet followed by the high fermentable fiber diet (P < 0.05). In conclusion, the fermentable fiber content of the diet had very little effect on the type and function of immune cells in peripheral blood. However, feeding dogs a high fermentable fiber diet for 2 weeks (after 2 weeks of consuming a low fermentable fiber diet) altered the T-cell composition of GALT and produced a higher mitogen response in the predominantly T cell tissues and a lower response in areas involved in B cell functions. In conclusion, the level of fermentable fiber in the diet appears to alter GALT properties. Further studies are required to determine the direct contribution of a high or low fiber diet to these changes and the physiological implications to the health of the animal.

Animals↗
PubMed2000

Shipment impairs lymphocyte proliferative responses to microbial antigens.

Lymphocyte proliferation assays (LPAs) are widely used to assess T-lymphocyte function of patients with human immunodeficiency virus infection and other primary and secondary immunodeficiency disorders. Since these assays require expertise not readily available at all clinical sites, specimens may be shipped to central labs for testing. We conducted a large multicenter study to evaluate the effects of shipping on assay performance and found significant loss of LPA activity. This may lead to erroneous results for individual subjects and introduce bias into multicenter trials.

Candida↗
PubMed2026

Integrated Optimization, Genomic Characterization, and Functional Evaluation of Biogenic Selenium Nanoparticles from Bacillus licheniformis BLN313: Antibacterial and Anticancer Potential.

Microbial synthesis of selenium nanoparticles (SeNPs) offers a sustainable alternative to chemical routes, but the genetic basis of selenium handling in Bacillus remains poorly defined, which limits rational strain selection. Here, SeNP production, physicochemical characterization, and closed-genome sequencing are combined for Bacillus licheniformis BLN313. Selenite reduction peaked at 500 &#xb5;g/mL Na2SeO3 (88.8% conversion; 444 &#xb1; 27 &#xb5;g/mL Se0); at higher concentrations, conversion efficiency and viability diverged, indicating that tolerance and reductive capacity are distinct traits. Purified SeNPs were spherical and partially crystalline trigonal Se0 (TEM 190 &#xb1; 52 nm; DLS 166 nm, PDI 0.03; zeta potential -20.8 mV), carrying a proteinaceous capping layer confirmed by XPS, EDS, and FTIR and shown by LC-MS to be enriched in cell wall-derived metabolites. The particles were bactericidal against Micrococcus luteus (MIC 62.5 &#xb5;g/mL) and Klebsiella pneumoniae (MIC 250 &#xb5;g/mL) and reduced MCF-7 viability (IC50 2.7 &#xb5;g/mL) while sparing MCF-10A cells. The 4.11 Mb genome (46.3% GC; ANI 99.7%, dDDH 97.8%) encodes SulP and Pit transporters, multiple trxB copies, and sulfur-metabolism and oxidative-stress genes, defining a candidate gene set for selenium uptake, reduction and detoxification. BLN313 thus provides a genetically defined platform for SeNP production in biomedical and environmental applications.

Selenium↗
PubMed2002

Relationship of prebiotics and food to intestinal microflora.

Dietary carbohydrates that escape digestion in the small intestine, undergo bacterial fermentation in the colon. This process affects the microbial ecology of the gastrointestinal tract and influences gut metabolism and function. Prebiotics are non-digestible but fermentable oligosaccharides that are specifically designed to change the composition and activity of the intestinal microbiota with the prospect to promote the health of the host. Dietary fiber and non-digestible oligosaccharides are the main growth substrates of gut microorganisms. Their fermentation results in the acidification of the colonic contents and the formation of short chain fatty acids which serve as fuels in different tissues and may play a role in the regulation of cellular processes. Prebiotics specifically stimulate the growth of endogenous microbial population groups such as bifidobacteria and lactobacilli which are perceived as being beneficial to human health. In spite of the interesting nutritional properties of prebiotics it is questionable whether a wholesome diet rich in fruit and vegetables needs to be supplemented with prebiotics for optimal health effects.

Bacteria↗
PubMed2002

Anaerobic infections in the surgical patient: microbial etiology and therapy.

Anaerobic infections occur in surgical patients in part because of structural or functional defects in the host that (1) cause a breech in the normal mucosal barriers, (2) create localized vascular insufficiencies, or (3) produce an obstruction. Any or all of these events may compromise the oxidation-reduction potential within the tissues, encouraging rapid anaerobic growth. Although diverse anaerobic populations are spread throughout the gastrointestinal tract, a relatively limited number of organisms are responsible for clinical infection in the surgical patient. Many of these offending organisms express overt virulence factors that enhance microbial adherence, tissue destruction, and, in the case of Bacteroides fragilis, facilitate abscess formation. The selection of an appropriate perioperative or therapeutic agent requires a fundamental knowledge of the microbial ecology of this microbial population. The failure to consider the anaerobic flora as a component in the etiology of mixed surgical infections is associated with a high rate of perioperative and therapeutic failures.

Bacteria, Anaerobic↗
PubMed2006

Lipids as renewable resources: current state of chemical and biotechnological conversion and diversification.

Oils and fats are the most important renewable raw materials of the chemical industry. They make available fatty acids in such purity that they may be used for chemical conversions and for the synthesis of chemically pure compounds. Oleic acid (1) from "new sunflower," linoleic acid (2) from soybean, linolenic acid (3) from linseed, erucic acid (4) from rape seed, and ricinoleic acid (5) from castor oil are most important for chemical transformations offering in addition to the carboxy group one or more C-C-double bonds. New plant oils containing fatty acids with new and interesting functionalities such as petroselinic acid (6) from Coriandrum sativum, calendic acid (7) from Calendula officinalis, alpha-eleostearic acid (8) from tung oil, santalbic acid (9) from Santalum album (Linn.), and vernolic acid (10) from Vernonia galamensis are becoming industrially available. The basic oleochemicals are free fatty acids, methyl esters, fatty alcohols, and fatty amines as well as glycerol as a by-product. Their interesting new industrial applications are the usage as environmentally friendly industrial fluids and lubricants, insulating fluid for electric utilities such as transformers and additive to asphalt. Modern methods of synthetic organic chemistry including enzymatic and microbial transformations were applied extensively to fatty compounds for the selective functionalization of the alkyl chain. Syntheses of long-chain diacids, omega-hydroxy fatty acids, and omega-unsaturated fatty acids as base chemicals derived from vegetable oils were developed. Interesting applications were opened by the epoxidation of C-C-double bonds giving the possibility of photochemically initiated cationic curing and access to polyetherpolyols. Enantiomerically pure fatty acids as part of the chiral pool of nature can be used for the synthesis of nonracemic building blocks.

Biotechnology↗