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At least 451 records · Page 25Linked to original sources
PubMed2003

Dendritic cells: interfaces with immunobiology and medicine. A report from the Keystone Symposia Meeting held in Keystone, 3-8 March 2003.

Dendritic cells (DCs) are the most potent antigen-presenting cells in vitro and in vivo. They play a key role in the initiation of the immune response and are considered promising targets for immunotherapy. The recent DC Keystone Symposia, organized by Ralph M Steinman, Anne O'Garra and Jacques Banchereau, was held on 3-8 March 2003 in Keystone (CO, USA). This multidisciplinary meeting developed various areas related to the DC biology including: (i) DC and the control of immunity vs tolerance; (ii) DC maturation and manipulation for immunotherapy in vivo; and (iii) antigen capture by DC in situ and interactions with microbial pathogens. The aim of this report is to present some of the highlights developed during the meeting and debated among the DC community.

Animals↗
PubMed1999

The microbiology of infected and noninfected leg ulcers.

BACKGROUND: A clinical study was undertaken to investigate and compare specifically the aerobic and anaerobic microbiology of infected and noninfected leg ulcers. METHODS: Leg ulcers, defined as being infected on the basis of clinical signs, were swab sampled and investigated for aerobic and anaerobic microorganisms using stringent isolation and identification techniques. RESULTS: Two hundred and twenty isolates were cultured from 44 infected leg ulcers, in comparison with 110 isolates from 30 noninfected leg ulcers. Statistical analysis indicated a significantly greater mean number of anaerobic bacteria per infected ulcer (particularly Peptostreptococcus spp. and Prevotella spp.) in comparison with the noninfected ulcer group (2.5 vs. 1.3, respectively) (P < 0.05). Also, anaerobes represented 49% of the total microbial composition in infected leg ulcers compared with 36% in noninfected leg ulcers. The mean numbers of aerobes per wound in the two ulcer groups were not statistically different (P > 0.05). The study failed to demonstrate a clear correlation between commonly implicated facultative pathogens and wound infection. The isolation rate of Pseudomonas aeruginosa was generally low and, although Staphylococcus aureus was a frequent isolate in both wound types, it was more prevalent in noninfected leg ulcers. CONCLUSIONS: This study has demonstrated the complex aerobic-anaerobic microflora which exists in leg ulcers, the prevalence of anaerobes in infected wounds, and a poor correlation between the presence of specific aerobic pathogens and wound infection. In view of these findings, the role of microbial synergistic interactions in the pathogenesis of chronic wound infection may be of greater clinical importance than the isolated involvement of any specific potential pathogen.

Anti-Bacterial Agents↗
PubMed2003

Breaking the species barrier: use of SCID mouse-human chimeras for the study of human infectious diseases.

Mouse-human chimeras have become a novel way to model the interactions between microbial pathogens and human cells, tissues or organs. Diseases studied with human xenografts in severe combined immunodeficient (SCID) mice include Pseudomonas aeruginosa infection in cystic fibrosis, group A streptococci and impetigo, bacillary and amoebic dysentery, and AIDS. In many cases, disease in the human xenograft appears to accurately reproduce the disease in humans, providing a powerful model for identifying virulence factors, host responses to infection and the effects of specific interventions on disease. In this review, we summarize recent studies that have used mouse-human chimeras to understand the pathophysiology of specific bacterial and protozoan infections.

Animals↗
PubMed1982

Dietary fiber and cholesterol and bile acid metabolisms in axenic (germfree) and holoxenic (conventional) rats. II. Effect of pectin.

Axenic and holoxenic rats were fed with a semi-synthetic diet containing 5 p. 100 pectin as the only fiber. Although the microbial flora of the digestive tract converted most of the bile acids in holoxenic rats, it hardly changed the other characteristics of cholesterol and bile acid metabolisms, except intestinal bile salt pools which were much larger in the axenic rats. When the pectin-containing and pectin-free diets were compared, it appeared that the former diet increased cecal weight, especially in axenic rats, but slightly modified cholesterol and bile acid metabolisms. However, the values of some characteristics of those metabolisms varied individually in the holoxenic rat fed with the pectin-containing diet, while they were very homogeneous in the other groups. This heterogeneity might result from pectin-digestive tract microbial flora interactions which would vary among individuals.

Aging↗
PubMed2001

Helicobacter pylori infection in children.

A number of scientific breakthroughs since H pylori first became recognized as a human pathogen have increased our understanding of the pathogenesis of gastroduodenal disease. In particular, advances in molecular bacteriology and the complete sequencing of the H pylori genome in 1999, and soon thereafter the human genome, provide tools allowing better delineation of the pathogenesis of disease. These molecular tools for both bacteria and host should now be applied to multicenter pediatric studies that evaluate disease outcome. More recent developments indicate that a better understanding of the microbial-host interaction is critical to furthering knowledge with respect to H pylori-induced diseases. Studies are needed to evaluate either DNA-based or more traditional protein-based vaccines, to evaluate more specific antimicrobials that confer minimal resistance, and to evaluate probiotics for the management of H pylori infection. Multicenter multinational studies of H pylori infection in the pediatric population, which include specific, randomized controlled eradication trials, are essential to extend current knowledge and develop better predictors of disease outcome.

Abdominal Pain↗
PubMed2002

Chemical warfare between microbes promotes biodiversity.

Evolutionary processes generating biodiversity and ecological mechanisms maintaining biodiversity seem to be diverse themselves. Conventional explanations of biodiversity such as niche differentiation, density-dependent predation pressure, or habitat heterogeneity seem satisfactory to explain diversity in communities of macrobial organisms such as higher plants and animals. For a long time the often high diversity among microscopic organisms in seemingly uniform environments, the famous "paradox of the plankton," has been difficult to understand. The biodiversity in bacterial communities has been shown to be sometimes orders of magnitudes higher than the diversity of known macrobial systems. Based on a spatially explicit game theoretical model with multiply cyclic dominance structures, we suggest that antibiotic interactions within microbial communities may be very effective in maintaining diversity.

Anti-Bacterial Agents↗
PubMed1994

Use of genetic recombination as a reporter of gene expression.

An understanding of the patterns of gene expression in response to specific environmental signals can yield insight into a variety of complex biological systems such as microbial-host interactions, developmental cycles, cellular differentiation, ontogeny, etc. To extend the utility of the reporter gene fusion approach to such studies, we have constructed a gene expression reporter cassette that permits the generation of transcriptional fusions to tnpR encoding resolvase, a site-specific recombinase of the transposable element gamma delta. Induction of the transcriptional fusions results in production of resolvase, which in turn, catalyzes excision of a linked tetracycline-resistance reporter gene flanked by direct repeats of res, the DNA sequences at which resolvase functions. The loss of tetracycline resistance in descendant bacteria serves as a permanent and heritable marker of prior gene expression. This gene fusion approach will allow us to assay the induction of gene expression in as few as one cell. Additionally, gene expression can be assayed at a later time and/or different place from the inducing environment facilitating the study of gene expression in complex environments such as animal tissues.

Alkaline Phosphatase↗
PubMed2003

Calpain regulates enterocyte brush border actin assembly and pathogenic Escherichia coli-mediated effacement.

This study identifies calpain as being instrumental for brush border (BB) microvillus assembly during differentiation and effacement during bacterial pathogenesis. Calpain activity is decreased by 25-80% in Caco 2 lines stably overexpressing calpastatin, the physiological inhibitor of calpain, and the effect is proportional to the calpastatin/calpain ratio. These lines exhibit a 2.5-fold reduction in the rate of microvillus extension. Apical microvillus assembly is reduced by up to 50%, as measured by quantitative fluorometric microscopy (QFM) of ezrin, indicating that calpain recruits ezrin to BB microvilli. Calpain inhibitors ZLLYCHN2, MDL 28170, and PD 150606 block BB assembly and ezrin recruitment to the BB. The HIV protease inhibitor ritonavir, which inhibits calpain at clinically relevant concentrations, also blocks BB assembly, whereas cathepsin and proteasome inhibitors do not. Microvillus effacement is inhibited after exposure of calpastatin-overexpressing cells to enteropathogenic Escherichia coli. These results suggest that calpain regulates BB assembly as well as pathological effacement, and indicate that it is an important regulator involved in HIV protease inhibitor toxicity and host-microbial pathogen interactions.

Actins↗
PubMed2001

Dendritic cells as vectors for vaccination against infectious diseases.

Antigen presentation by dendritic cells (DCs) is critical for the induction of a specific immune response. The immunotherapeutic potential of antigen-pulsed DCs for the treatment of cancer has been confirmed in a number of experimental tumor models and in several preclinical trials. Recent advances in our understanding of the interaction of microbial pathogens with DCs have provided the basis to explore DCs as vaccine carriers for the induction of protective immune responses to infections. Support for this strategy comes from animal studies demonstrating that DCs, after ex vivo loading with microbial antigens, confer protection against microbial challenges in vivo. This may have important implications for the development of novel strategies for prophylactic or therapeutic immunizations against various microbial pathogens.

Animals↗
PubMed1986

Improved method for estimation of azole antifungal inhibitory concentrations against Candida species, based on azole/antibiotic interactions.

Low, reproducible minimal inhibitory concentrations against Candida species, with sharp, precise end points in complex media were achieved for imidazoles (clotrimazole, econazole, miconazole, tioconazole and ketoconazole) and triazoles (fluconazole, itraconazole, vibunazole, ICI 153066) by including in the test medium antibacterial antibiotics that bind to the 80S eukaryotic ribosome and inhibit protein synthesis, i.e. blasticidin, cycloheximide, doxycycline, neomycin and gentamicin. The presence of these antibiotics reduced MICs, on average, by 50- to 250-fold. Other protein synthesis inhibitors (rifampicin, erythromycin, lincomycin, clindamycin, chloramphenicol and fusidic acid) were not effective, and the antibiotics did not affect MICs for Aspergillus species. The low azole MICs were in close agreement with MICs obtained in a defined, tissue culture-based medium lacking added antibiotics.

Anti-Bacterial Agents↗
PubMed1990

In vitro comparison of the activity of cefotaxime and desacetylated cefotaxime and of their combination.

The activity of cefotaxime (CTX), desacetylcefotaxime (dCTX) and their combinations (CTX and dCTX in a 1:1 ratio) was tested against a variety of aerobic and anaerobic bacteria collected from clinical specimens. The in-vitro tests demonstrated that CTX is still active against a wide range of clinically interesting microorganisms. The interaction of CTX and dCTX was shown to be additive at subinhibitory and inhibitory concentrations for Enterobacteriaceae. The most significant increase in the antibacterial activity was seen against Bacteroides strains: 29% of 62 strains were sensitive to CTX and 38% to CTX plus dCTX.

Bacteria↗
PubMed2005

Bacterial peptidoglycan-associated lipoprotein: a naturally occurring toll-like receptor 2 agonist that is shed into serum and has synergy with lipopolysaccharide.

Sepsis is initiated by interactions between microbial products and host inflammatory cells. Toll-like receptors (TLRs) are central innate immune mediators of sepsis that recognize different components of microorganisms. Peptidoglycan-associated lipoprotein (PAL) is a ubiquitous gram-negative bacterial outer-membrane protein that is shed by bacteria into the circulation of septic animals. We explored the inflammatory effects of purified PAL and of a naturally occurring form of PAL that is shed into serum. PAL is released into human serum by Escherichia coli bacteria in a form that induces cytokine production by macrophages and is tightly associated with lipopolysaccharide (LPS). PAL activates inflammation through TLR2. PAL and LPS synergistically activate macrophages. These data suggest that PAL may play an important role in the pathogenesis of sepsis and imply that physiologically relevant PAL and LPS are shed into serum and act in concert to initiate inflammation in sepsis.

Animals↗
PubMed2002

Genomes to Life "Center for Molecular and Cellular Systems": a research program for identification and characterization of protein complexes.

Goal 1 of Department of Energy's Genomes to Life (GTL) program seeks to identify and characterize the complete set of protein complexes within a cell. Goal 1 forms the foundation necessary to accomplish the other objectives of the GTL program, which focus on gene regulatory networks and molecular level characterization of interactions in microbial communities. Together this information would allow cells and their components to be understood in sufficient detail to predict, test and understand the responses of a biological system to its environment. The Center for Molecular and Cellular Systems has been established to identify and characterize protein complexes using high through-put analytical technologies.A dynamic research program is being developed that supports the goals of the Center by focusing on the development new capabilities for sample preparation and complex separations, molecular level identification of the protein complexes by mass spectrometry, characterization of the complexes in living cells by imaging techniques, and bioinformatics and computational tools for the collection and interpretation of data and formation of databases and tools to allow the data to be shared by the biological community.

Animals↗
PubMed2026

Computational tool choice impacts CRISPR spacer-protospacer detection.

MOTIVATION: CRISPR spacer-protospacer matching is widely used to infer host-virus interactions in microbial and viromics studies, but the choice of sequence search or alignment tool and its reporting behavior is often under-evaluated for this specific task. RESULTS: Using synthetic, semi-synthetic, and real datasets, we benchmarked commonly used tools and observed substantial differences in recall, runtime, and resource usage across distance metrics and thresholds. Our analyses support practical defaults for large-scale spacer-target matching and clarify trade-offs between exhaustive and heuristic approaches. AVAILABILITY: Source code and benchmark workflows are available at https://github.com/UriNeri/spacer_matching_bench. Data and run artifacts are archived on Zenodo (https://doi.org/10.5281/zenodo.15171878).

Software↗
PubMed1986

In-vitro activity of cefoperazone-sulbactam against Bacteroides species.

The in-vitro activity of two combinations of sulbactam and cefoperazone against 187 strains of Bacteroides fragilis were evaluated; their activity was compared with that of the drugs alone, and correlated with the production of beta-lactamase by the bacterial strains. The results indicated that both combinations had a synergistic effect: the addition of 8 mg/l of sulbactam to the MIC of cefoperazone reduced the percentage of resistant strains from 58% to 0.5%; while the combination of two parts of cefoperazone to one pact of sulbactam lowered the resistance rate to 1%. Synergy was observed most frequently with beta-lactamase positive strains, but it also occurred among beta-lactamase negative strains.

Bacteria, Anaerobic↗
PubMed1987

Interaction between ciprofloxacin and vancomycin against staphylococci.

The interaction between ciprofloxacin and vancomycin against nine isolates of Staphylococcus epidermidis from cases of infective endocarditis and three strains of S. aureus was studied. Killing curves indicated the presence of antagonism in the early stages, the clinical significance of which is uncertain. No synergy was found and the combination therefore does not appear to offer any advantages over vancomycin alone for the treatment of staphylococcal infections.

Ciprofloxacin↗