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PubMed2003

Antimicrobial peptides: current status and therapeutic potential.

Antimicrobial peptides (AMPs) are effector molecules of the innate immune system. A variety of AMPs have been isolated from species of all kingdoms and are classified based on their structure and amino acid motifs. AMPs have a broad antimicrobial spectrum and lyse microbial cells by interaction with biomembranes. Besides their direct antimicrobial function, they have multiple roles as mediators of inflammation with impact on epithelial and inflammatory cells influencing diverse processes such as cell proliferation, immune induction, wound healing, cytokine release, chemotaxis and protease-antiprotease balance. AMPs qualify as prototypes of innovative drugs that may be used as antimicrobials, anti-lipopolysaccharide drugs or modifiers of inflammation. Several strategies have been followed to identify lead candidates for drug development, to modify the peptides' structures, and to produce sufficient amounts for pre-clinical and clinical studies. This review summarises the current knowledge about the basic and applied biology of AMPs.

Animals↗
PubMed2005

Probiotic research in Australia, New Zealand and the Asia-Pacific region.

Although the epicentres of probiotic research in the past decade have been Japan and Europe, researchers in the Asia-Pacific region have actively contributed to the growing understanding of the intestinal microbial ecosystem, and interactions between gut bacteria, diet and health of the human host. A number of new probiotic strains have been developed in the region that have been demonstrated to have beneficial impacts on health in animal and human trials, including improved protection against intestinal pathogens and modulation of the immune system. Probiotics targeted to animals, including aquaculture, feature heavily in many Asian countries. Developments in probiotic technologies have included microencapsulation techniques, antimicrobial production in fermented meats, and synbiotic combinations. In particular, the impact of resistant starch on the intestinal environment and fermentation by intestinal bacteria has been intensively studied and new probiotic strains selected specifically for synbiotic combinations with resistant starch. This paper provides an overview of probiotic research within Australia, New Zealand and a number of Asian countries, and lists scientists in the Asia-Pacific region involved in various aspects of probiotic research and development.

Academies and Institutes↗
PubMed2005

Functions of antimicrobial peptides in host defense and immunity.

Antimicrobial peptides (AMPs) are effector molecules of the innate immune system. AMPs have a broad antimicrobial spectrum and lyse microbial cells by interaction with biomembranes. Besides their direct antimicrobial function, they have multiple roles as mediators of inflammation with impact on epithelial and inflammatory cells influencing diverse processes such as cytokine release, cell proliferation, angiogenesis, wound healing, chemotaxis, immune induction, and protease-antiprotease balance. Furthermore, AMPs qualify as prototypes of innovative drugs that may be used as antibiotics, anti-lipopolysaccharide drugs, or modifiers of inflammation. This review summarizes the current knowledge about the basic and applied biology of antimicrobial peptides and discusses features of AMPs in host defense and inflammation.

Amino Acid Sequence↗
PubMed1994

Concentrations of folates in ruminal content of steers: responses to a dietary supplement of folic acid in relation with the nature of the diet.

In an attempt to evaluate the ruminal effects of dietary supplements of folic acid, eight steers (352 +/- 27 kg BW) fitted with a ruminal cannula were randomly assigned to a replicated 4 x 4 Latin square design. The treatments were 70% rolled barley + 30% timothy hay (HC), HC + 2 mg of folic acid per kilogram of BW (HC + FA), 30% rolled barley + 70% timothy hay (HF), and HF + 2 mg of folic acid per kilogram of BW (HF + FA). After 5 wk of adaptation to the dietary treatments, ruminal contents were sampled over three consecutive days, at 1, 2, 4, 8, 12, and 23 h after feed distribution. Concentrations of folates in solid and liquid ruminal fractions were increased by the dietary supplement of folic acid (P = .0001) and by the ingestion of concentrate compared with hay-based diets (P < .05). Preprandial concentrations of serum folates were not affected by the nature of the diet when steers received no folic acid but the increase of serum folates induced by the dietary supplement of folic acid was more important in steers fed concentrates than in those fed hay-based diets (diet x supplement of folic acid interaction P = .002). Microbial protein (P = .004) and microbial mass (P = .002) in ruminal fluid were increased with concentrate-based diets compared with hay-based diets; folic acid did not have any effect on these variables (P > .05). In conclusion, concentrations of folates in ruminal contents were affected by dietary supplements of folic acid and by the nature of the diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMed1986

Evaluation of alfalfa-corn cob associative action. III. The effect of mechanically separated alfalfa fractions on intake, digestibility and ruminal characteristics of ammonia-treated corn cob diets fed to sheep.

The influence of mechanically separated alfalfa fractions on intake, digestibility and rate of ruminal passage was investigated using 48 lambs (32 kg) in a digestion trial. Whole plant pre-bloom alfalfa (25% crude protein) or fractions (presscake, dehydrated presscake, protein coagulum, dehydrated protein coagulum, whole juice or deproteinized juice) were added to a 3% ammonia (NH3)-treated corn cob negative control diet at levels equal to 20% wholeplant alfalfa dry matter (DM); eight treatments, six lambs/treatment. Ad libitum intake was greater (P less than .05) for alfalfa fiber (presscake) or juice supplemented diets compared with 20% direct cut alfalfa. Dry matter intake, digestibility of DM and cell walls, and rate of passage were highly correlated when diets were fed ad libitum. At equal DM intakes, dehydrated vs wet presscake increased (P less than .05) DM and cell wall digestibility. Heating of the protein may have reduced degradation rate and consequently a slower release of nutrients for microorganisms in the rumen. Whole vs deproteinized juice increased digestibility of cob DM (P = .11) and cell walls (P = .13), suggesting a response to level of degradable alpha-amino N. Whole and deproteinized juice increased cell wall digestibility compared with the negative control by 23.0 and 18.5 percentage units, respectively, suggesting that degradable alpha amino-N and cell solubles or other nutrients interacted to maximize microbial fiber digestion. Total and branch-chain volatile fatty acids measured at 6, 12 and 18 h post-feeding were highly correlated with nutrient digestibility. Ruminal NH3-N measured at 18 h was negatively correlated with dry matter (r = -.74) and cell wall (r = -.72) digestibility, showing that alfalfa supplies nutrients required by ruminal microorganisms for NH3 assimilation and fiber digestion. The mode of alfalfa associative action in high fiber diets is in supplying ruminal microorganisms with degradable protein and (or) other nutrients, rather than altering ruminal retention time.

Ammonia↗
PubMed1985

Current concepts in periodontal diseases.

Periodontal diseases are common oral diseases that afflict all humans to some degree. The major aetiological agent is dental plaque--the complex microflora which forms on teeth in the absence of effective oral hygiene. The interaction of the microbial flora and the periodontal tissues produces an inflammatory response and tissue breakdown. Recent information has categorized periodontal diseases on the basis of increased knowledge about the particular microorganisms associated with the different clinical conditions. In addition, the important role of host defences, in particular the phagocytic cellular elements, has allowed for a better understanding of the pathological processes. This knowledge is contributing towards the development of rational and effective therapy for all forms of periodontal diseases. Because of the widespread occurrence of periodontal diseases and their potential relationships to systemic conditions, it is important that medical practitioners should be able to recognize, and be conversant with methods of treatment of, these diseases.

Acute Disease↗
PubMed1999

Cutting edge: bacterial DNA and LPS act in synergy in inducing nitric oxide production in RAW 264.7 macrophages.

LPS is well recognized for its potent capacity to activate mouse macrophages to produce NO, an important inflammatory mediator in innate host defense. We demonstrate here that, although inducing little NO alone, DNA from both Gram-negative and Gram-positive bacteria synergizes with subthreshold concentrations of LPS (0.3 ng/ml) to induce NO in cultures of RAW 264.7 macrophages. The effects of the DNA are mimicked by synthetic CpG-containing oligodeoxynucleotides but not by non-CpG-containing oligodeoxynucleotides. This synergistic activity is not inhibited by neutralizing Abs against IFN. Preincubation of macrophages with DNA for 8-24 h suppresses subsequent synergistic macrophage responses to DNA/LPS, whereas prolonged pretreatment with LPS enhances synergy. RT-PCR analysis indicates that the mRNA levels of the inducible NO synthase gene are also coordinately suppressed or induced. These findings indicate that temporally controlled, synergistic interactions exist between microbial DNA and LPS in the induction of macrophage NO via enhanced inducible NO synthase gene expression.

Animals↗
PubMed2000

Large-scale synthesis and functional elements for the antimicrobial activity of defensins.

Human neutrophil defensins, and their analogues incorporating anionic, hydrophobic or cationic residues at the N- and C-termini, were synthesized by solid-phase procedures. The synthetic defensins were examined for their microbicidal activity against Candida albicans, two Gram-negative bacteria (Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis) and two Gram-positive bacteria (Streptococcus gordonii and Streptococcus mutans). The human neutrophil peptide 1 (HNP1) and HNP2 were found to be potent candidacidal agents. HNP3, which differs by one amino acid at the N-terminus of its sequence, was totally inactive. The Gram-negative bacteria A. actinomycetemcomitans and P. gingivalis and the Gram-positive bacteria S. gordonii and S. mutans were insensitive to human defensins. However, the insertion of two basic residues, such as arginine, at both the N-terminus and the C-terminus of HNP2 significantly enhanced antifungal and antibacterial activity. The addition of anionic residues, such as aspartic acid, at the N- and C-termini rendered the molecule totally inactive. The presence of two hydrophobic amino acids, such as valine, at the N-terminus of HNP2 and of two basic arginine residues at its C-terminus resulted in molecules that were optimally active against these oral pathogens. The results suggest that the N- and C-terminal residues in defensin peptides are the crucial functional elements that determine their microbicidal potency. The three-dimensional structure of all defensins constitutes the same amphiphilic beta-sheet structure, with the polar face formed by the N- and C-terminal residues playing an important role in defining microbicidal potency and the antimicrobial spectrum. The enhanced microbicidal activity observed for defensin peptides with two basic residues at both the N- and C-termini could be due to optimization of the amphiphilicity of the structure, which could facilitate specific interactions with the microbial membranes.

Aggregatibacter actinomycetemcomitans↗
PubMed2006

[Three cases of tuberculosis children who demonstrated paradoxical worsening during different stage of treatment].

We report three tuberculosis children aged seven-month-old to 11-year-old who had paradoxical worsening of tuberculosis of lung and lymph nodes, lymph nodes, and intracranial tuberculoma at different treatment stages. In these children, paradoxical worsening occurred at about 14 days after start of anti-tuberculosis treatment, about six months after the start, and about three months after the completion of treatment. No alteration was done in the method of anti-tuberculosis treatment against expanding lesions, and predonisolone was prescribed in two subjects. Expanded lesions then improved one- to five-months later. The mechanisms of paradoxical worsening is unclear. However, these cases suggest that paradoxical worsening may occur at any time after starting anti-tuberculosis treatment based on interaction between the microbial factors and host immunological factors in lung, lymph nodes, intracranial tuberculosis lesions.

Child↗
PubMed1983

Definitions of infectious and infectious-like conditions in the lower genital tract of the female.

A large number of factors regulate the composition and dynamics of the microbial ecosystems in the lower female genito-urinary tract. Metabolic activities of certain species of e.g. the vaginal microbial community might give rise to symptomatic infectious-like conditions without activation of the host's defense mechanisms. On the other hand, "true" infections might pass without any obvious symptoms. Similar to other mucosal surfaces, the microbial ecosystems on the periurethral, introital, vaginal and urethral mucosa is dominated by anaerobic bacteria. Some of the infectious-like conditions in the lower female genito-urinary tract involve predominantly anaerobic bacteria of the endogenous flora. A "dynamic" thinking including considerations of microbial and host/parasite interactions is currently replacing the concept of "one microorganism-one disease". The traditionally used clinical terminology has not kept pace with the modern ecological views. We have emphasize the need for unequivocal and strictly defined criteria for the clinical definitions of infectious and infectious-like conditions in the lower female genito-urinary tract.

Adolescent↗
PubMed2026

In silico analysis and comparison of the metabolic capabilities of different organisms by reducing metabolic complexity.

BACKGROUND: Understanding how metabolic capabilities diverge across microbial species is essential for deciphering community function, ecological interactions, and the design of synthetic microbiomes. Despite shared core pathways, microbial phenotypes can differ markedly due to evolutionary adaptations and metabolic specialization. Genome-scale metabolic models (GEMs) provide a systems-level framework to explore these differences; however, their complexity hinders direct comparison. RESULTS: We introduce NIS (Neidhardt-Ingraham-Schaechter), a computational workflow that integrates the redGEM, lumpGEM, and redGEMX algorithms to systematically reduce genome-scale models into biologically interpretable modules. This approach enables direct, quantitative comparison of fueling pathways, biomass biosynthetic routes, and environmental exchange processes while retaining essential metabolic information. We first demonstrate the utility of NIS by analyzing Escherichia coli and Saccharomyces cerevisiae, which revealed both conserved and divergent strategies in central metabolism, biosynthetic cost, and substrate utilization. We then applied NIS to the core honeybee gut microbiome, uncovering distinct metabolic traits, functional redundancy, and complementarity that help explain auxotrophy, cross-feeding interactions, and microbial coexistence. CONCLUSIONS: NIS provides an automated, scalable, and reproducible framework for dissecting microbial metabolic networks beyond gene content or taxonomy. By linking metabolism to ecological function, NIS offers new opportunities to interpret microbial community dynamics and to support the rational design of microbiomes in health, agriculture, and environmental applications. Video Abstract.

Metabolic Networks and Pathways↗
PubMed2000

Relative contributions of bacteria, protozoa, and fungi to in vitro degradation of orchard grass cell walls and their interactions.

To assess the relative contributions of microbial groups (bacteria, protozoa, and fungi) in rumen fluids to the overall process of plant cell wall digestion in the rumen, representatives of these groups were selected by physical and chemical treatments of whole rumen fluid and used to construct an artificial rumen ecosystem. Physical treatments involved homogenization, centrifugation, filtration, and heat sterilization. Chemical treatments involved the addition of antibiotics and various chemicals to rumen fluid. To evaluate the potential activity and relative contribution to degradation of cell walls by specific microbial groups, the following fractions were prepared: a positive system (whole ruminal fluid), a bacterial (B) system, a protozoal (P) system, a fungal (F) system, and a negative system (cell-free rumen fluid). To assess the interactions between specific microbial fractions, mixed cultures (B+P, B+F, and P+F systems) were also assigned. Patterns of degradation due to the various treatments resulted in three distinct groups of data based on the degradation rate of cell wall material and on cell wall-degrading enzyme activities. The order of degradation was as follows: positive and F systems > B system > negative and P systems. Therefore, fungal activity was responsible for most of the cell wall degradation. Cell wall degradation by the anaerobic bacterial fraction was significantly less than by the fungal fraction, and the protozoal fraction failed to grow under the conditions used. In general, in the mixed culture systems the coculture systems demonstrated a decrease in cellulolysis compared with that of the monoculture systems. When one microbial fraction was associated with another microbial fraction, two types of results were obtained. The protozoal fraction inhibited cellulolysis of cell wall material by both the bacterial and the fungal fractions, while in the coculture between the bacterial fraction and the fungal fraction a synergistic interaction was detected.

Animals↗
PubMed2000

Nucleic acid-based fluorescent probes in microbial ecology: application of flow cytometry.

Microorganisms in natural environments have often been treated as 'black box' systems. Researchers have measured the inputs and outputs of the box, and have made bulk measurements on cell behaviour. However, unravelling the details of the diversity and interactions that exist within these microbial populations has proven exceptionally difficult. The information gained from the black box approach has been invaluable, and has allowed models of global foodwebs to be generated and tested. However, there is still little information about the interactions of individual microbial cells within natural populations. Such studies are essential to fully understand the integrated functioning of ecosystems. To achieve this goal, researchers need to be able to identify individual cells within a population, enumerate them, estimate both viability and activity, and monitor changes in response to relevant parameters. Due to the diversity, heterogeneity and numbers of cells that make up these populations, these measurements require automation and speed. At present, the use of flow cytometry in conjunction with nucleic acid probes provides an excellent method with which to pursue such studies.

Bacteria↗
PubMed2026

Cross-domain cooperation drives nutrient acquisition and metabolism in the bark beetle holobiont.

Microbial symbiosis underpins host adaptation, yet mechanisms of metabolic integration in holobionts remain unclear. Using metatranscriptomics, genomics, and metabolic assays, we investigated gut microbiome interactions in the European spruce bark beetle (Ips typographus). We observed metabolic complementarity among symbionts and host, forming cross-domain networks that support nutrient acquisition. Nitrogen recycling revealed strong interdependence: no single partner possessed a complete uric acid degradation pathway, but combined evidence supports a distributed pathway spanning beetle, Bacteria, and fungi. Additionally, bacterial nitrate reduction to ammonia indicates a potential nitrogen influx, making otherwise inaccessible inorganic nitrogen available to the host. Shaped by microbial interactions, symbionts also likely supply specific amino acids, while vitamin metabolism showed cross-domain co-metabolism, with Bacteria as main producers of B vitamins, while host and fungi modulated interconversion. Carbohydrate degradation was highly partitioned; bacteria target xylan and pectin, while fungi contribute to glucan breakdown. Crucially, our data provide indirect evidence that the beetle may contribute to complete cellulose degradation, highlighting an underappreciated host role in lignocellulose processing. In terms of enzymatic functional diversity, the bacteriome emerged as the most important microbiome component-an observation that contrasts with the traditional focus on fungi and underscores the need to consider bacterial contributions in insect symbioses. Despite life-stage variation, core metabolic functions remained stable. Overall, metabolic interdependence, rather than microbial composition alone, structures holobiont function. These results highlight functional redundancy and ecological resilience, emphasizing the importance of microbial cooperation and host-microbe metabolic evolution.

Bark beetle↗
PubMed1991

Anti-infective therapy in intensive care units.

In intensive care units, treatment is primarily directed at the suspected pathogen. However, the risk of interaction with other concomitantly administered drugs, the possible accumulation when renal and, in particular, hepatic function are impaired, and the possible development of resistance play major roles when selecting a therapeutic regimen. Studies of interactions between the different antimicrobial substances and, in particular, interactions between the antibiotics and other drugs are urgently called for in the future.

Anti-Infective Agents↗
PubMed2002

Microbial diversity and function in soil: from genes to ecosystems.

Soils sustain an immense diversity of microbes, which, to a large extent, remains unexplored. A range of novel methods, most of which are based on rRNA and rDNA analyses, have uncovered part of the soil microbial diversity. The next step in the era of microbial ecology is to extract genomic, evolutionary and functional information from bacterial artificial chromosome libraries of the soil community genomes (the metagenome). Sophisticated analyses that apply molecular phylogenetics, DNA microarrays, functional genomics and in situ activity measurements will provide huge amounts of new data, potentially increasing our understanding of the structure and function of soil microbial ecosystems, and the interactions that occur within them. This review summarizes the recent progress in studies of soil microbial communities with focus on novel methods and approaches that provide new insight into the relationship between phylogenetic and functional diversity.

Bacteria↗