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Results for “Host Microbial Interactions”

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PubMed2006

Host defense peptides and lipopeptides: modes of action and potential candidates for the treatment of bacterial and fungal infections.

Endogenous peptide antibiotics (termed also host-defense or antimicrobial peptides) are known as evolutionarily old components of innate immunity. They were found initially in invertebrates, but later on also in vertebrates, including humans. This secondary, chemical immune system provides organisms with a repertoire of small peptides that act against invasion (for both offensive and defensive purposes) by occasional and obligate pathogens. Each antimicrobial peptide has a broad but not identical spectrum of antimicrobial activity, predominantly against bacteria, providing the host maximum coverage against a rather broad spectrum of microbial organisms. Many of these peptides interact with the target cell membranes and increase their permeability, which results in cell lysis. A second important family includes lipopeptides. They are produced in bacteria and fungi during cultivation on various carbon sources, and possess a strong antifungal activity. Unfortunately, native lipopeptides are non-cell selective and therefore extremely toxic to mammalian cells. Whereas extensive studies have emerged on the requirements for a peptide to be antibacterial, very little is known concerning the parameters that contribute to antifungal activity. This review summarizes recent studies aimed to understand how antimicrobial peptides and lipopeptides select their target cell. This includes a new group of lipopeptides highly potent against pathogenic fungi and yeast. They are composed of inert cationic peptides conjugated to aliphatic acids with different lengths. Deep understanding of the molecular mechanisms underlying the differential cells specificity of these families of host defense molecule is required to meet the challenges imposed by the life-threatening infections.

Bacterial Infections↗

PubMed1998

Selected animal models: vaginal candidosis, Pneumocystis pneumonia, dermatophytosis and trichosporosis.

A clear understanding of the pathogenesis of fungal disease remains elusive. While technological advances in molecular biology and microbial genetics have provided scientists with major new insights into both microbial virulence factors as well as host susceptibility to infection, there is currently no substitute for animal models in elucidating microbe-host interactions. Animal models are also essential for the evaluation of new antimicrobial agents, including studies of efficacy, adverse reactions and pharmacokinetics. The single most important advance in animal models in the last decade, has been the availability of genetically unique strains of animals as alternative to animals treated with immunosuppressive drugs for use in studies on microbial virulence and host defence mechanisms. These unique strains of test animals also enhance our understanding of the modes of action of antifungal drugs and their metabolism. Some of these advances will be discussed in this symposium.

Animals↗

PubMed2004

Microbial dynamics and interactions in the spermosphere.

The spermosphere represents a short-lived, rapidly changing, and microbiologically dynamic zone of soil surrounding a germinating seed. It is analogous to the rhizosphere, being established largely by the carbon compounds released into the soil once the seed begins to hydrate. These seed exudations drive the microbial activities that take place in the spermosphere, many of which can have long-lasting impacts on plant growth and development as well as on plant health. In this review, I discuss the nature of the spermosphere habitat and the factors that give rise to its character, with emphasis on the types of microbial activities in the spermosphere that have important implications for disease development and biological disease control. This review, which represents the first comprehensive synthesis of the literature on spermosphere biology, is meant to illustrate the unique nature of the spermosphere and how studies of interactions in this habitat may serve as useful experimental models for testing hypotheses about plant-microbe associations and microbial ecology.

Animals↗

PubMed2026

Parallel single-cell host immune profiling and pathogen genomic characterization in Klebsiella-associated sepsis: a pilot study.

OBJECTIVES: Sepsis is a life-threatening syndrome characterized by profound immune dysregulation and substantial biological heterogeneity. Here, we conducted a pilot study to explore host immune remodeling in Klebsiella-associated sepsis by combining single-cell RNA sequencing of peripheral blood mononuclear cells with whole-genome sequencing of the corresponding bloodstream isolates. METHODS: In this prospective observational pilot study, we analyzed peripheral blood mononuclear cells (PBMCs) from two patients with Klebsiella-associated sepsis and two healthy controls (HC) using single-cell RNA sequencing. PBMC composition, differential transcriptional responses, and pathway analysis were assessed across immune subsets. The corresponding bloodstream isolates were characterized by phenotypic antimicrobial susceptibility testing and whole-genome sequencing. RESULTS: Compared to HC, septic patients showed expansion of the myeloid compartment and contraction of the NK/T compartment. High-resolution analysis suggested shifts within lymphoid populations. At the transcriptional level, sepsis was associated with compartment-specific enrichment of interferon-related and host-defence pathways, as well as oxidative phosphorylation, ATP synthesis, and mitochondrial electron transport signatures across multiple PBMC subsets. Classical monocytes exhibited a coordinated decrease in MHC class II-related transcripts. The sepsis-associated isolates were identified as Klebsiella pneumoniae and Klebsiella variicola and were notable for overall antimicrobial susceptibility, limited resistomes, and absence of canonical hypervirulence determinants. CONCLUSION: Our data provide a preliminary description of immune remodeling during Klebsiella-associated sepsis and suggest that severe clinical disease may be associated with isolates lacking classical multidrug-resistance or hypervirulence features. These findings should be interpreted as preliminary and hypothesis-generating and require validation in larger cohorts with detailed clinical severity assessment.

Female↗

PubMed1974

Host-Pathogen Interactions: VII. Plant Pathogens Secrete Proteins which Inhibit Enzymes of the Host Capable of Attacking the Pathogen.

The results presented demonstrate that microbial pathogens of plants have the ability to secrete proteins which effectively inhibit an enzyme synthesized by the host; an enzyme whose substrate is a constituent of the cell wall of the pathogen. The system in which this was discovered is the anthracnose-causing fungal pathogen (Colletotrichum lindemuthianum) and its host, the French bean (Phaseolus vulgaris). An endo-beta-1, 3-glucanase present in the bean leaves is specifically inhibited by a protein secreted by C. lindemuthianum. The cell walls of C. lindemuthianum are shown to be composed largely of a 1, 3-glucan.

Journal Article↗

PubMed1994

[Factors on antimicrobials].

Infections which are difficult to cure are mainly caused by resistant organisms or opportunistic pathogens. For the treatment of such infections, we should maximize drug's therapeutic potentials, and minimize its toxicity. Characteristics of pharmacodynamics and pharmacokinetics in antimicrobials should be taken into account to maximize the efficacy and to minimize the toxicity. Bactericidal activity and post-antibiotic effect of antimicrobials are the major factors to determine the optimal dosing. Infections caused by intra-phagocytic pathogens should be treated with drugs which penetrate cell well. Early treatment with antimicrobials is the corner-stone for the treatment of infections in immunocompromised host. It is very important to determine which of the two drugs should be given first to maximize the efficacy on combination therapy.

Anti-Bacterial Agents↗

PubMed1980

Modulation of human polymorphonuclear leukocyte chemotaxis by leukocyte extracts, bacterial products, inflammatory exudates, and polyelectrolytes.

Human polymorphonuclear leukocytes (PMN) chemotaxis was tested during exposure to leukocyte and platelet extracts, a variety of polyelectrolytes, inflammatory exudates, and bacterial products. The chemoattractants employed were either zymosan-activated serum or supernatant from autolyzed Staphylococcus aureus. Chemotaxis to both chemoattractants was markedly inhibited by leukocyte and platelet extracts; inflammatory exudates; anionic polyelectrolytes, DNA, hyaluronic acid, liquoid; and by cationic polyelectrolytes, histone, protamine base, protamine sulfate, and myeloperoxidase. Inhibition was also found with elastase, collagenase, pepstatin, and epsilon-amino-caproic acid. Bacterial products, such as lipoteichoic acid and lipopolysaccharides, and extracts of human dental plaque inhibited chemotaxis. No inhibition of chemotaxis was observed with heparin (< 10 micrograms/ml), chondroitin sulfate, phosphatidylethanolamine and phospatidylserine. Indeed, chondroitin sulfate markedly enhanced chemotaxis and antagonized the inhibitory effect of leukocyte or platelet extract. None of the agents employed was toxic to PMN as judged by trypan blue exclusion. These observations suggest that cationic polyelectrolytes and inflammatory exudates influence PMN surfaces, modifying interaction with chemoattractants. Assessment of the role of PMN chemotaxis in host defense against microbial invaders requires evaluation of the response in the presence of agents likely to be present in inflamed tissues.

Chemotaxis, Leukocyte↗

PubMed2004

[Pathogenesis of ankylosing spondylitis-mechanisms of disease manifestation and chronicity].

Despite intensive research during the last three decades, it is still not clear which precise mechanisms determine the interactions between host factors (HLA-B27 and other genes, cytokines, T lymphocytes) and microbial factors leading to the manifestation and chronicity of ankylosing spondylitis (AS). Rheumatologists and histopathologists have focused their interest on decoding the immune-mediated inflammatory processes and on studying new bone formation and ankylosis. Concerning the genetic basis of AS, there is considerable effort in large genome-wide and candidate gene analyses to discover new genes that are associated with AS. Moreover, such genetic studies could identify genomic regions that determine clinical manifestations and the course of disease.

Autoimmune Diseases↗

PubMed2001

Anaphylatoxins and infectious and non-infectious inflammatory diseases.

In recent years a plethora of data has accumulated directing toward an important role of polypeptides C3a and C5a and its degradation product C5adesArg, summarized as anaphylatoxins (ATs), in microbial host defense and immune regulation. The ATs exert their various biologic functions by interacting with specific C3a- and C5a-receptors present on cells of myeloid origin, epithelial cells, smooth muscle cells as well as on activated B- and T-cells. Activation of AT receptors mediates signal transduction pathways triggering a variety of proinflammatory events. However, by interacting with the cytokine- and chemokine network C3a and C5a exhibit also anti-inflammatory properties. In this review the focus is on the pathogenetic role of the ATs in sepsis, immune complex disease, delayed type hypersensitivity and asthma. Discussed are data from animal models in which the ATs are blocked by specific C3a or C5a inhibitors or from mice with genetic deletions of the specific receptors of either C3a or C5a/C5adesArg.

Anaphylatoxins↗

PubMed1992

Propionibacterium acnes-metabolites inhibit experimental lung metastasis of murine sarcoma L-1 in BALB/c-mice.

Adhesive interactions between tumor cells and host tissue occur at several stages of metastasis. Such interactions might be inhibited by microbial metabolites resembling the binding regions of matrix molecules. Certain metabolite sequences including Gly, Asp, Arg, and Ser (GAAS) proved to be critical for cell interactions, e.g. with fibronectin. In vitro, the rosette formation of murine pulmonary cells and sarcoma L-1 cells decreased significantly in the presence of Propionibacterium acnes-metabolites rich in GAAS. In vivo, coinjection of Propionibacterium acnes-metabolites and sarcoma L-1 cells significantly inhibited the formation of lung colonies in BALB/c mice. The inhibition of lung colonization by these metabolites appeared to be noncytotoxic and obviously did not result from impairment of cellular tumorigenicity.

Amino Acid Sequence↗

PubMed1989

Immunomodulatory effects of Bacteroides products on in vitro human lymphocyte functions.

Bacteroides spp. have been implicated in the pathogenesis of several diseases, including periodontal diseases. In this study sonic extracts of 6 Bacteroides spp. were examined for their abilities to alter human lymphocyte function. We found that soluble extracts from Bacteroides intermedius, Bacteroides endodontalis, Bacteroides asaccharolyticus, Bacteroides melaninogenicus, and to a lesser degree Bacteroides loescheii, caused dose-dependent inhibition of human lymphocyte responsiveness to both mitogens and antigens. Suppression involved altered DNA, RNA and protein synthesis as well as immunoglobulin production. In contrast, Bacteroides gingivalis did not suppress these responses; instead, it stimulated lymphocyte proliferation and enhanced immunoglobulin production. It has been proposed that impaired host defense may play a pivotal role in the pathogenesis of many infections. The data presented in this paper suggest that microbial mediated immunosuppression may conceivably alter the nature and consequences of host-parasite interactions in periodontal disease.

Bacteroides↗

PubMed1994

Saliva-bacterium interactions in oral microbial ecology.

Saliva is thought to have a significant impact on the colonization of microorganisms in the oral cavity. Salivary components may participate in this process by one of four general mechanisms: binding to microorganisms to facilitate their clearance from the oral cavity, serving as receptors in oral pellicles for microbial adhesion to host surfaces, inhibiting microbial growth or mediating microbial killing, and serving as microbial nutritional substrates. This article reviews information pertinent to the molecular interaction of salivary components with bacteria (primarily the oral streptococci and Actinomyces) and explores the implications of these interactions for oral bacterial colonization and dental plaque formation. Knowledge of the molecular mechanisms controlling bacterial colonization of the oral cavity may suggest methods to prevent not only dental plaque formation but also serious medical infections that may follow microbial colonization of the oral cavity.

Actinomyces↗

PubMed2006

Robustness trade-offs and host-microbial symbiosis in the immune system.

The immune system provides organisms with robustness against pathogen threats, yet it also often adversely affects the organism as in autoimmune diseases. Recently, the molecular interactions involved in the immune system have been uncovered. At the same time, the role of the bacterial flora and its interactions with the host immune system have been identified. In this article, we try to reconcile these findings to draw a consistent picture of the host defense system. Specifically, we first argue that the network of molecular interactions involved in immune functions has a bow-tie architecture that entails inherent trade-offs among robustness, fragility, resource limitation, and performance. Second, we discuss the possibility that commensal bacteria and the host immune system constitute an integrated defense system. This symbiotic association has evolved to optimize its robustness against pathogen attacks and nutrient perturbations by harboring a broad range of microorganisms. Owing to the inherent propensity of a host immune system toward hyperactivity, maintenance of bacterial flora homeostasis might be particularly important in the development of preventive strategies against immune disorders such as autoimmune diseases.

Bacteria↗

PubMedDate not supplied

Strategic targets of essential host-pathogen interactions.

This review summarizes the present concepts regarding the biological processes that mediate intrinsic and innate host defense against microbial invasion of the lung. Innate immunity is the first line of defense of the higher organisms towards invading pathogens. It accomplishes a wide variety of activities including recognition and effector functions. The innate responses use phagocytic cells (macrophages, monocytes, and neutrophils), cells that release inflammatory mediators (basophils, mast cells, and eosinophils), and natural killer cells. The molecular component of innate responses includes complement, acute-phase proteins, and cytokines. Recognition of pathogen-associated molecular patterns is mediated by the pathogen receptors of the innate immune system, among these molecules toll-like receptors have emerged as fundamental components in the innate immune responses to infection, and a link between innate and adaptive immunity. Additional protection comes from polypeptide mediators of the innate host defense, such as the defensins and other antibiotic peptides. In view of the considerable burden in terms of mortality and morbidity that severe infections still pose worldwide, a better understanding of the biological basis of host-pathogen interactions opens stimulating future treatment perspectives.

Animals↗

PubMed2001

Microarrays for studying the host transcriptional response to microbial infection and for the identification of host drug targets.

It is essential to understand the molecular basis of a host's response to microbial infection so that disease and tissue damage can be prevented. Modulation of host RNA expression is a critical set of molecular changes that occur upon infection. Global analysis of gene expression should provide an understanding of host RNA transcriptional changes that occur upon host-pathogen interaction. This series of articles focuses on the use of microarrays for analyzing the transcriptional response of a host to microbial infection and for drug target identification.

Animals↗

PubMed2026

Ecological and methodological insights from genetic and coprological profiling of gastrointestinal communities in wild howler monkeys.

The gastrointestinal tract hosts a complex community of microorganisms and helminth parasites that collectively contribute to host health and fitness. Analysis of these communities provides insight into diverse aspects of host dietary ecology, immunity, nutrition, and host-parasite interactions. However, research methodologies, such as sample preservation and sequencing approach, can influence how we understand and characterize these features. Here, we profiled the gastrointestinal microbial and helminth communities in different groups of wild Costa Rican mantled howler monkeys (Alouatta palliata palliata). We compared samples stored in ethanol versus directly flash frozen, and contrasted conclusions drawn from 16S versus shotgun sequencing approaches. Bacterial, archaeal, and eukaryotic taxa associated with the digestion of plant material dominated the GI communities. Storage and sequencing methods influenced microbial profiles: ethanol-stored samples exhibited higher diversity than frozen samples, and 16S sequencing detected lower diversity than shotgun. Helminths were detected via coprological microscopy in 71% of individuals, whereas metagenomic detection was inconsistent. This study provides new data on the microorganisms and their putative digestive functions in the gut of a folivorous primate, and highlights the pros and cons of different methodological choices when profiling host-microbiome and host-parasite interactions.

Animals↗

PubMed2004

Cellular and molecular effects of macrolides on leukocyte function.

Macrolide antimicrobials have stimulated worldwide interest owing to their therapeutic effects in various inflammatory, apparently non infectious, diseases. Abundant data are now available on their interactions with host cell (specially phagocyte) functions. Modulation of oxidant production by neutrophils and of pro-inflammatory cytokine synthesis and release by leukocytes are the two main effects observed in vitro. However, despite an extensive literature, many questions remain, such as the cellular/microbial target(s) of macrolide action, the critical chemical structure(s), and the usefulness of combining antimicrobial and anti-inflammatory properties, which during long-term treatment, could lead to increased microbial resistance. Also, because of the multiplicity of macrolide effects on different cell subsets, a unifying hypothesis for macrolide interactions with host cells is lacking. Novel analytical methods will certainly lead to new macrolide-based therapeutic strategies in cancer and inflammation.

Animals↗

PubMed2003

Reactive oxygen intermediates in plant-microbe interactions: who is who in powdery mildew resistance?

Reactive oxygen intermediates (ROIs) such as hydrogen peroxide (H(2)O(2)) and the superoxide anion radical (O*(2)(-)) accumulate in many plants during attack by microbial pathogens. Despite a huge number of studies, the complete picture of the role of ROIs in the host-pathogen interaction is not yet fully understood. This situation is reflected by the controversially discussed question as to whether ROIs are key factors in the establishment and maintenance of either host cell inaccessibility or accessibility for fungal pathogens. On the one hand, ROIs have been implicated in signal transduction as well as in the execution of defence reactions such as cell wall strengthening and a rapid host cell death (hypersensitive reaction). On the other hand, ROIs accumulate in compatible interactions, and there are reports suggesting a function of ROIs in restricting the spread of leaf lesions and thus in suppressing cell death. Moreover, in situ analyses have demonstrated that different ROIs may trigger opposite effects in plants depending on their spatiotemporal distribution and subcellular concentrations. This demonstrates the need to determine the particular role of individual ROIs in distinct stages of pathogen development. The well-studied interaction of cereals with fungi from the genus Blumeria is an excellent model system in which signal transduction and defence reactions can be further elucidated in planta. This review article gives a synopsis of the role of ROI accumulation, with particular emphasis on the pathosystem Hordeum vulgare L.- Blumeria graminis.

Disease Susceptibility↗