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PubMed2002

[The influence of bioceramics on phagocytosis of human leukocytes].

BACKGROUND: After implantation of biomaterials in the regions of head and neck with resident microbial contamination the interaction between the implant and microbes play an important role for the success of the implantation. The host immune defence is important for the outcome after implantation, too. Phagocytosis plays an important role in the human immune response on infections. MATERIAL AND METHODS: The method described by Suess was used to investigate and measure the influence of the bioceramics Bioverit((R)) and Al(2)O(3)-ceramic on phagocytosis of yeast by human leukocytes. RESULTS: The bioceramics showed no statistically significant influence on phagocytosis function by human leukocytes. There was a tendency towards lower phagocytosis rates in all samples with bioceramics. CONCLUSIONS: The bioceramics Bioverit((R)) and Al(2)O(3) ceramic have no influence on phagocytosis of human leukocytes. In conclusion these biomaterials did not cause any inhibition of this important part of the human immune response on microbial infections after alloplastic implantation in head and neck regions.

Adult↗

PubMed2000

Seasonal population dynamics and interactions of competing bacteriophages and their host in the rhizosphere.

We describe two prolonged bacteriophage blooms within sugar beet rhizospheres ensuing from an artificial increase in numbers of an indigenous soil bacterium. Further, we provide evidence of in situ competition between these phages. This is the first in situ demonstration of such microbial interactions in soil. To achieve this, sugar beet seeds were inoculated with Serratia liquefaciens CP6RS or its lysogen, CP6RS-ly-phi 1. These were sown, along with uninoculated seeds, in 36 field plots arranged in a randomized Latin square. The plots were then sampled regularly over 194 days, and the plants were assayed for the released bacteria and any infectious phages. Both the lysogen and nonlysogen forms of CP6RS survived equally well in situ, contradicting earlier work suggesting lysogens have a competitive disadvantage in nature. A Podoviridae phage, identified as phi CP6-4, flourished on the nonlysogen-inoculated plants in contrast to those plants inoculated with the lysogen. Conversely, the Siphoviridae phage phi CP6-1 (used to construct the released lysogen) was isolated abundantly from the lysogen-treated plants but almost never on the nonlysogen-inoculated plants. The uninoculated plants also harbored some phi CP6-1 phage up to day 137, yet hardly any phi CP6-4 phages were found, and this was consistent with previous years. We show that the different temporal and spatial distributions of these two physiologically distinct phages can be explained by application of optimal foraging theory to phage ecology. This is the first time that such in situ evidence has been provided in support of this theoretical model.

Chenopodiaceae↗

PubMed2005

Bacteria-host-cell interactions at the plasma membrane: stories on actin cytoskeleton subversion.

Exploitation of the host-cell actin cytoskeleton is pivotal for many microbial pathogens to enter cells, to disseminate within and between infected tissues, to prevent their uptake by phagocytic cells, or to promote intimate attachment to the cell surface. To accomplish this, these pathogens have evolved common as well as unique strategies to modulate actin dynamics at the plasma membrane, which will be discussed here, exemplified by a number of well-studied bacterial pathogens.

Actins↗

PubMed2002

Antibiotic production by bacterial biocontrol agents.

Interest in biological control of plant pathogens has been stimulated in recent years by trends in agriculture towards greater sustainability and public concern about the use of hazardous pesticides. There is now unequivocal evidence that antibiotics play a key role in the suppression of various soilborne plant pathogens by antagonistic microorganisms. The significance of antibiotics in biocontrol, and more generally in microbial interactions, often has been questioned because of the indirect nature of the supporting evidence and the perceived constraints to antibiotic production in rhizosphere environments. Reporter gene systems and bio-analytical techniques have clearly demonstrated that antibiotics are produced in the spermosphere and rhizosphere of a variety of host plants. Several abiotic factors such as oxygen, temperature, specific carbon and nitrogen sources, and microelements have been identified to influence antibiotic production by bacteria biocontrol agents. Among the biotic factors that may play a determinative role in antibiotic production are the plant host, the pathogen, the indigenous microflora, and the cell density of the producing strain. This review presents recent advances in our understanding of antibiotic production by bacterial biocontrol agents and their role in microbial interactions.

Anti-Bacterial Agents↗

PubMed1994

Neutrophils, host defense, and inflammation: a double-edged sword.

Neutrophils play important roles in host defense against all classes of infectious agents but, paradoxically, they are also involved in the pathology of various inflammatory conditions. Their microbicidal armory consists of oxidative and nonoxidative processes that are activated simultaneously upon phagocytosis. Although destruction of infectious agents occurs intracellularly, release of cytotoxic molecules into the extracellular milieu can damage body tissues. Neutrophils are heterogeneous. Subpopulations exist in various stages from dormant to primed to fully activated. The activities of neutrophils are regulated locally in microenvironments and systemically by a plethora of mediators including cytokines, "classical" neuroendocrine hormones, and bioactive lipids. The net response depends on a complex balance of stimulatory and inhibitory pathways that are regulated by these mediators. Although some effector and regulatory pathways are vital, considerable redundancy is also evident. Identification of the essential mediators and the unraveling of any interactions may be the keys to understanding the neutrophil paradox and developing therapeutic strategies that optimize microbial killing and minimize host tissue damage. Finally, reports that neutrophils can act as drug delivery vectors and that their function is influenced by stress and other lifestyle factors suggest that new homeostatic functions for these cells, outside their traditional roles in host defense and inflammation, remain to be identified: some are speculated on here.

Humans↗

PubMed2022

Ecological dynamics of plasmid transfer and persistence in microbial communities.

Plasmids are a major driver of horizontal gene transfer in prokaryotes, allowing the sharing of ecologically important accessory traits between distantly related bacterial taxa. Within microbial communities, interspecies transfer of conjugative plasmids can rapidly drive the generation genomic innovation and diversification. Recent studies are starting to shed light on how the microbial community context, that is, the bacterial diversity together with interspecies interactions that occur within a community, can alter the dynamics of conjugative plasmid transfer and persistence. Here, I summarise the latest research exploring how community ecology can both facilitate and impose barriers to the spread of conjugative plasmids within complex microbial communities. Ultimately, the fate of plasmids within communities is unlikely to be determined by any one individual host, rather it will depend on the interacting factors imposed by the community in which it is embedded.

Bacteria↗

PubMed2004

[Emerging rickettsioses].

Ticks are known to carry and transmit a number of microbial agents that cause diseases in humans and animals. Among these are members of the order Rickettsiales (alpha-proteobacteria), which include the genera Rickettsia and Ehrlichia. The most common and well-known Rickettsial human disease in Europe is Mediterranean Spotted Fever (MSF), caused by Rickettsia conorii. In recent years, a number of new Rickettsia species have been discovered in Europe, some of which have been shown to be pathogenic to humans. These discoveries have been facilitated by use of sequence-based molecular identification techniques. In Italy, it is generally believed that R. conorii is the only Rickettsia species present, and clinical tests for MSF rely on antigens raised against this bacterium. We are currently undertaking a molecular screening study of Rickettsiales-bacteria in ticks from various regions of Italy, to check for the potential presence of species from this order recently discovered in other parts of Europe. So far, we have identified a number of additional species in ticks collected from northern, central and southern regions. These include the known pathogens R. helvetica and R. slovaca as well as two species which may or may not be of medical relevance: R. monacensis and R. sp. IRS4. As a part of this survey, we have identified a novel alphaproteobacterium from the medically important tick Ixodes ricinus. This bacterium, tentatively named IricES1, has the unusual property of existing within the mitochondria, as well as the cytoplasm, of ovarian cells. To our knowledge, this is the only known example of a bacterium that is able to enter the mitochondria of animals. Our recently published electron microscopic data indicates that the bacterium enters mitochondria between the inner and outer membranes, and then proceeds to consume the inner mitochondrial matrix. We will present further data on this bacterium, including: 1) its phylogenetic position based on various molecular sequences, 2) its localization within the tick based on in situ hybridization; 3) its distribution among tick populations in Europe; 4) preliminary data on attempts at culturing this bacterium in a variety of cell types. Possible interactions between the bacterium and its host will be discussed. Ticks are known to carry and transmit a number of microbial agents that cause diseases in humans and animals. Among these are members of the order Rickettsiales (alpha-proteobacteria), which include the genera Rickettsia and Ehrlichia. The most common and well-known Rickettsial human disease in Europe is Mediterranean Spotted Fever (MSF), caused by Rickettsia conorii. In recent years, a number of new Rickettsia species have been discovered in Europe, some of which have been shown to be pathogenic to humans. These discoveries have been facilitated by use of sequence-based molecular identification techniques. In Italy, it is generally believed that R. conorii is the only Rickettsia species present, and clinical tests for MSF rely on antigens raised against this bacterium. We are currently undertaking a molecular screening study of Rickettsiales-bacteria in ticks from various regions of Italy, to check for the potential presence of species from this order recently discovered in other parts of Europe. So far, we have identified a number of additional species in ticks collected from northern, central and southern regions. These include the known pathogens R. helvetica and R. slovaca as well as two species which may or may not be of medical relevance: R. monacensis and R. sp. IRS4. As a part of this survey, we have identified a novel alphaproteobacterium from the medically important tick Ixodes ricinus. This bacterium, tentatively named IricES1, has the unusual property of existing within the mitochondria, as well as the cytoplasm, of ovarian cells. To our knowledge, this is the only known example of a bacterium that is able to enter the mitochondria of animals. Our recently published electron microscopic data indicates that the bacterium enters mitochondria between the inner and outer membranes, and then proceeds to consume the inner mitochondrial matrix. We will present further data on this bacterium, including: 1) its phylogenetic position based on various molecular sequences, 2) its localization within the tick based on in situ hybridization; 3) its distribution among tick populations in Europe; 4) preliminary data on attempts at culturing this bacterium in a variety of cell types. Possible interactions between the bacterium and its host will be discussed.

Animals↗

PubMed2004

Pharmacokinetic and pharmacodynamic issues in the treatment of bacterial infectious diseases.

This review outlines some of the many factors a clinician must consider when selecting an antimicrobial dosing regimen for the treatment of infection. Integration of the principles of antimicrobial pharmacology and the pharmacokinetic parameters of an individual patient provides the most comprehensive assessment of the interactions between pathogen, host, and antibiotic. For each class of agent, appreciation of the different approaches to maximize microbial killing will allow for optimal clinical efficacy and reduction in risk of development of resistance while avoiding excessive exposure and minimizing risk of toxicity. Disease states with special considerations for antimicrobial use are reviewed, as are situations in which pathophysiologic changes may alter the pharmacokinetic handling of antimicrobial agents.

Anti-Bacterial Agents↗

PubMed2004

Antigenic glycans in parasitic infections: implications for vaccines and diagnostics.

Infections by parasitic protozoans and helminths are a major world-wide health concern, but no vaccines exist to the major human parasitic diseases, such as malaria, African trypanosomiasis, amebiasis, leishmaniasis, schistosomiasis, and lymphatic filariasis. Recent studies on a number of parasites indicate that immune responses to parasites in infected animals and humans are directed to glycan determinants within cell surface and secreted glycoconjugates and that glycoconjugates are important in host-parasite interactions. Because of the tremendous success achieved recently in generating carbohydrate-protein conjugate vaccines toward microbial infections, such as Haemophilus influenzae type b, there is renewed interest in defining parasite-derived glycans in the prospect of developing conjugate vaccines and new diagnostics for parasitic infections. Parasite-derived glycans are compelling vaccine targets because they have structural features that distinguish them from mammalian glycans. There have been exciting new developments in techniques for glycan analysis and the methods for synthesizing oligosaccharides by chemical or combined chemo-enzymatic approaches that now make it feasible to generate parasite glycans to test as vaccine candidates. Here, we highlight recent progress made in elucidating the immunogenicity of glycans from some of the major human and animal parasites, the potential for developing conjugate vaccines for parasitic infections, and the possible utilization of these novel glycans in diagnostics.

Animals↗

PubMed2006

Infection and musculoskeletal conditions: Infectious arthritis.

In contrast to the outstanding achievements made in therapy for autoimmune arthritides, not least rheumatoid arthritis, the pace of progress in therapy for infectious arthritis remains slow. This has primarily to do with the complex task of, on the one hand, killing the invading microorganisms and, on the other, to down-regulate the exaggerated immune response which participates in the microbial clearance but at the same time contributes to the tissue destruction. The use of experimental models of microbial arthritides has clarified several bacterial virulence factors as well as many haematopoietic cell types and their products that are involved in the pathogenesis of joint infection. Recent studies have documented that T-cell-mediated responses are not only prominent but also decisive with respect to disease sequelae. This chapter also reviews the primarily protective non-antigen-specific immune responsiveness to microbial agents, including the impact of neutrophils, complement system, and nitric oxide. The knowledge gained regarding microbial virulence factors and the host immune responses has prompted researchers to develop new strategies on how to interact in vivo with the infectious process. Some of these approaches are commented upon in this review: e.g. vaccination procedures to prevent septic arthritis and sepsis, as well as therapeutic procedures to minimize joint damage during an ongoing infection.

Animals↗

PubMed2001

Pleiotropic roles of formyl peptide receptors.

FPR and FPRL1 belong to the seven-transmembrane, G protein-coupled chemoattractant receptor superfamily. Because of their capacity to interact with bacterial chemotactic formylated peptides, these receptors are thought to play a role in host defense against microbial infection. Recently, a variety of novel agonists have been identified for these receptors, including several host-derived endogenous molecules that are involved in proinflammatory responses. Most notably is the use of FPRL1 by at least three amyloidogenic protein and peptide ligands, the serum amyloid A (SAA), the 42 amino acid form of beta amyloid (Abeta(42)), and the prion peptide PrP106-126, to chemoattract and activate human phagocytic leukocytes. These new findings have greatly expanded the functional scope of the formyl peptide receptors and call for more in-depth investigation of the role of these receptors in pathophysiological conditions.

Amyloidosis↗

PubMed2002

Toward an understanding of microbial communities through analysis of communication networks.

Bacteria receive signals from diverse members of their biotic environment. They sense their own species through the process of quorum sensing, which detects the density of bacterial cells and regulates functions such as bioluminescence, virulence, and competence. Bacteria also respond to the presence of other microorganisms and eukaryotic hosts. Most studies of microbial communication focus on signaling between the microbe and one other organism for empirical simplicity and because few experimental systems offer the opportunity to study communication among various types of organisms. But in the real biological world, microorganisms must carry on multiple molecular conversations simultaneously between diverse organisms, thereby constructing communication networks. We propose that biocontrol of plant disease, the process of suppressing disease through application of a microorganism, offers a model for the study of communication among multiple organisms. Successful biocontrol requires the sending and receiving of signals between the biocontrol agent and the pathogen, plant host, and microbial community surrounding the host. We are using Bacillus cereus, a biocontrol agent, and the organisms it must interact with, to dissect a communication network. This system offers an excellent starting point for study because its members are defined and well studied. An understanding of signaling in the B. cereus biocontrol system may provide a model for network communication among organisms that share a habitat and provide a new angle of analysis for understanding the interconnections that define communities.

Bacillus cereus↗

PubMed2005

Peptide mapping of bacterial fimbrial epitopes interacting with pattern recognition receptors.

The fimbriae of the oral pathogen Porphyromonas gingivalis induce Toll-like receptor 2 (TLR2)-dependent macrophage activation upon their recognition by CD14 and the beta(2) integrin CD11b/CD18. To map functional epitopes of fimbriae that interact with these pattern recognition receptors (PRRs), we examined 20 synthetic peptides covering the entire length of the 41-kDa fimbrillin subunit. Using direct or competitive inhibition assays for receptor binding or cell activation, the CD14 binding activity of fimbriae was localized to residues 69-90 and was essential for TLR2-dependent cytokine induction. The CD11b/CD18 binding activity of fimbriae was localized to two neighboring epitopes defined by residues 166-185 and 206-225. Unlike epitope 69-90 that constitutively bound CD14, the CD11b/CD18 binding activity of epitopes 166-185 and 206-225 was inducible by integrin activators. The CD11b/CD18 binding activity played a contributory role to TLR2-dependent induction of tumor necrosis factor-alpha by fimbriae but was involved in specific down-regulation of interleukin-12. Cell activation by a combination of fimbrillin peptides corresponding to the CD14 and CD11b/CD18 binding activities resulted in higher tumor necrosis factor-alpha responses than would be expected from a simply additive effect, attributable to CD14-dependent inside-out signaling leading to enhanced binding interactions with CD11b/CD18. These data suggest that P. gingivalis fimbriae display a modular structure that interacts through discrete epitopes and in a regulated mode with distinct PRRs, which in turn differentially modulate the state of cell activation. Elucidation of pathogen interactions with PRRs at the molecular level may glean insight into host defense mechanisms as well as into microbial strategies that subvert innate immunity.

Amino Acid Sequence↗

PubMed1998

Topics in dose-response modeling.

Great uncertainty exists in conducting dose-response assessment for microbial pathogens. The data to support quantitative modeling of dose-response relationships are meager. Our philosophy in developing methodology to conduct microbial risk assessments has been to rely on data analysis and formal inferencing from the available data in constructing dose-response and exposure models. The probability of illness is a complex function of factors associated with the disease triangle: the host, the pathogen, and the environment including the food vehicle and indigenous microbial competitors. The epidemiological triangle and interactions between the components of the triangle are used to illustrate key issues in dose-response modeling that impact the estimation of risk and attendant uncertainty. Distinguishing between uncertainty (what is unknown) and variability (heterogeneity) is crucial in risk assessment. Uncertainty includes components that are associated with (i) parameter estimation for a given assumed model, and (ii) the unknown "true" model form among many plausible alternatives such as the exponential, Beta-Poisson, probit, logistic, and Gompertz. Uncertainty may be grossly understated if plausible alternative models are not tested in the analysis. Examples are presented of the impact of variability and uncertainty on species, strain, or serotype of microbial pathogens; variability in human response to administered doses of pathogens; and effects of threshold and nonthreshold models. Some discussion of the usefulness and limitations of epidemiological data is presented. Criteria for development of surrogate dose-response models are proposed for pathogens for which human data are lacking. Alternative dose-response models which consider biological plausibility are presented for predicting the probability of illness.

Adult↗

PubMed1995

Isolation and characterization of fibronectin-binding sites of Borrelia garinii N34.

Adherence of bacteria to host cell membranes is one of the initial steps of microbial pathogenicity. Numerous studies have suggested that fibronectin promotes this interaction in some bacterial species. In this study, we have examined the ability of Borrelia garinii to bind fibronectin. The binding of fibronectin to the spirochete was specific and saturable. Scatchard plot analysis of the binding data revealed two types of ligands on the spirochetal surface, one with high affinity and one with low affinity for fibronectin. The fibronectin-binding sites were solubilized from the surface of B. garinii N34 by lysozyme treatment. Fast protein liquid chromatography (FPLC) purification of the solubilized binding sites resulted in one band with a high fibronectin-binding activity and a molecular weight of ca. 147,000. FPLC-purified binding sites, fibronectin, and antibodies to fibronectin inhibited the adherence of the spirochete to epithelial cells competitively. These data provide strong support for the hypothesis that fibronectin-binding sites on the surface of B. garinii are involved in the adherence of the spirochete to their respective host cells.

Bacterial Adhesion↗

PubMed1997

Role of oxidants in microbial pathophysiology.

Reactive oxidant species (superoxide, hydrogen peroxide, hydroxyl radical, hypohalous acid, and nitric oxide) are involved in many of the complex interactions between the invading microorganism and its host. Regardless of the source of these compounds or whether they are produced under normal conditions or those of oxidative stress, these oxidants exhibit a broad range of toxic effects to biomolecules that are essential for cell survival. Production of these oxidants by microorganisms enables them to have a survival advantage in their environment. Host oxidant production, especially by phagocytes, is a counteractive mechanism aimed at microbial killing. However, this mechanism may be contribute to a deleterious consequence of oxidant exposure, i.e., inflammatory tissue injury. Both the host and the microorganism have evolved complex adaptive mechanisms to deflect oxidant-mediated damage, including enzymatic and nonenzymatic oxidant-scavenging systems. This review discusses the formation of reactive oxidant species in vivo and how they mediate many of the processes involved in the complex interplay between microbial invasion and host defense.

Animals↗

PubMed1996

Effects of ozone upon macrophage-interferon interactions.

Lung cell populations may be directly exposed to environmental airbone toxicants such as ozone (O3). Since pulmonary macrophages (M phi) play a pivotal role in host pulmonary immunocompetence, their function in this regard may be compromised by pollutant exposure thereby giving rise to an increased incidence of pulmonary disease. The current in vitro study was designed to provide some insight into possible mechanisms by which O3 induces decreased host pulmonary resistance against microbial pathogens. Specifically, this study investigated the impact of an acute O3 exposure upon the ability of a cultured mouse M phi cell line (WEHI-3) to interact with, and respond to, the major M phi-activating cytokine, interferon-gamma (IFN gamma). The results of this study indicate that WEHI-3 exposure to 1 ppm O3 for 4 h reduced both the binding of, and responsivity to, IFN gamma. Among the functional parameters affected by this inability to properly bind/respond to IFN gamma were: reactive oxygen intermediate production, phagocytic activity, and cellular calcium ion elevation; IFN gamma-enhanced expression of surface histocompatibility antigens was unaffected by O3 exposure. The reduced activity of any one of these critical M phi functions could provide a basis for previously-documented increases in microbial pathogen survival in the lungs, and overall compromise of host health following O3 exposure.

Animals↗

PubMed2025

In silico encounters: harnessing metabolic modelling to understand plant-microbe interactions.

Understanding plant-microbe interactions is vital for developing sustainable agricultural practices and mitigating the consequences of climate change on food security. Plant-microbe interactions can improve nutrient acquisition, reduce dependency on chemical fertilizers, affect plant health, growth, and yield, and impact plants' resistance to biotic and abiotic stresses. These interactions are largely driven by metabolic exchanges and can thus be understood through metabolic network modelling. Recent developments in genomics, metagenomics, phenotyping, and synthetic biology now enable researchers to harness the potential of metabolic modelling at the genome scale. Here, we review studies that utilize genome-scale metabolic modelling to study plant-microbe interactions in symbiotic, pathogenic, and microbial community systems. This review catalogues how metabolic modelling has advanced our understanding of the plant host and its associated microorganisms as a holobiont. We showcase how these models can contextualize heterogeneous datasets and serve as valuable tools to dissect and quantify underlying mechanisms. Finally, we consider studies that employ metabolic models as a testbed for in silico design of synthetic microbial communities with predefined traits. We conclude by discussing broader implications of the presented studies, future perspectives, and outstanding challenges.

Plants↗