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Bacterial adherence. Adhesin receptor-mediated attachment of pathogenic bacteria to mucosal surfaces.

Pathogenic bacteria adhere to and colonize mucosal surfaces of the susceptible host in a highly selective manner. After the organisms penetrate the nonspecific mechanical and cleansing forces, ligands (or adhesins) on the surface of the bacteria interact in a lock-and-key fashion with complementary receptors on mucosal surfaces of the host. The adhesins are usually composed of proteins in the form of fimbriae or fibrillae and the receptors of glycolipids or glycoproteins. At the epithelial cell surfaces, two classic examples of bacterial adherence are the lipoteichoic acid-mediated attachments of group A streptococcal and the type 1 fimbriae-mediated attachment of Escherichia coli. In group A streptococci, the adhesin, lipoteichoic acid (LTA), is anchored to a protein(s) on the surface of the bacterial cells and interacts through its lipid moiety with fibronectin molecules deposited on and bound to the epithelial cells. In type 1 fimbriated E. coli, a minor 29-kDa protein located at the tip of the fimbriae interacts with D-mannose residues of glycoprotein receptors on host cells. Similar adhesin-receptor interactions have now been described for a number of pathogenic microbial agents, and undoubtedly play a central role in the early steps of the infectious process.

Bacterial Adhesion↗

Molecular mechanisms of NF-kappaB activation induced by bacterial lipopolysaccharide through Toll-like receptors.

Septic shock, caused by exaggerated host responses to various microbial products typified by lipopolysaccharide (LPS), remains the leading cause of death in trauma patients. Gaining insight into the nature of host interactions with LPS will certainly facilitate attempts to develop effective anti-sepsis drugs. Tremendous progress has been made during the past few years in understanding the mechanisms of pathogen-induced host responses. Toll-like receptor (TLR) 4 and 2 have been implicated as major receptors for signaling initiated by LPS and many other microbial products following their binding to CD14. In addition, many signaling intermediates involved in LPS-induced cell activation, particularly activation of the transcription factor NF-kappaB, have been identified and characterized. Further investigations with these molecules will certainly reward us with more effective therapeutic drugs to treat septic shock as well as many other inflammatory and infectious disorders.

Animals↗

Impact of genomics on microbial food safety.

Genome sequences are now available for many of the microbes that cause food-borne diseases. The information contained in pathogen genome sequences, together with the development of themed and whole-genome DNA microarrays and improved proteomics techniques, might provide tools for the rapid detection and identification of such organisms, for assessing their biological diversity and for understanding their ability to respond to stress. The genomic information also provides insight into the metabolic capacity and versatility of microbes; for example, specific metabolic pathways might contribute to the growth and survival of pathogens in a range of niches, such as food-processing environments and the human host. New concepts are emerging about how pathogens function, both within foods and in interactions with the host. The future should bring the first practical benefits of genome sequencing to the field of microbial food safety, including strategies and tools for the identification and control of emerging pathogens.

Biofilms↗

Current concepts of bacterial infections of the central nervous system. Bacterial meningitis and bacterial brain abscess.

Investigative work continues to provide guidance toward more rational management of bacterial meningitis and bacterial brain abscess. An increased understanding of the host's response in cases of bacterial meningitis has established that diffusibility of an antibiotic into the cerebrospinal fluid (CSF) is necessary, but is not sufficient for microbial cure. The antibiotic must also have a bactericidal effect on the pathogen. Meningitis after neurosurgery may be caused by Gram-negative aerobic bacilli. In some of these cases the newer cephalosporin antibiotics may be a useful advance. Meningitis complicating ventricular CSF shunts presents a paradigm for the problem of eradicating foreign body-related infections. Studies of the interaction of the host, the organism, and the shunt material offer some explanation for the limited efficacy of antibiotics observed in this setting. There have been advances in microbial definition of bacterial brain abscess. The identification of Bacteroides fragilis as a pathogen in certain brain abscesses has established a role for a newly available antibiotic, metronidazole. The study of the pathological distinction between cerebritis and frank abscess is clarifying two clinical characteristics of brain abscess: the limited success of antibiotic treatment and the increase in intracranial pressure. Computerized tomography has offered a valuable clinical "look" at brain abscesses; however, there are still problems in correlating the scan images with the evolving pathological process.

Adrenal Cortex Hormones↗

Bacterial adhesins: function and structure.

Specific adhesion to host tissue cells is an essential virulence factor of most bacterial pathogens. The fundamental processes that determine bacterial attachment to host tissue surfaces are mediated by microbial adhesins. Host specificity and tissue tropism are characteristics exhibited by different bacteria and are determined (at least in part) by the interaction between adhesins and their complementary receptors on host cell surfaces. A detailed picture of how bacteria are able to target to various receptors is emerging. A large number of bacterial adhesins with individual receptor specificities have been identified. Furthermore, recent research has shown that individual adhesins are prone to rapid microevolution that results in changes in the receptor specificity of individual adhesins. Microbial adhesins are often assembled into complex polymeric organelle structures, however non-organelle adhesins linked to the cell surface as monomers or simple oligomers also exist. This review gives an overview of bacterial adhesins and focuses on some general aspects of their biogenesis and role in bacterial colonization of host cell surfaces and as virulence factors.

Adhesins, Bacterial↗

Oral microbial communities in sickness and in health.

The relationship between humans and their oral microflora begins shortly after birth and lasts a lifetime. Up until fairly recently, the associations between the host and oral bacteria were considered in terms of a multiplicity of single species interactions. However, it is becoming more apparent that the oral microbes comprise a complex community, and that oral health or disease depends on the interface between the host and the microbial community as a whole. Although it is important to continue studies of the pathogenic properties of specific microbes, these are relevant only in the context of the properties of the community within which they reside. Understanding the microbial communities that drive sickness or health is a key to combating human oral diseases.

Bacteria↗

Intestinal epithelial tight junctions as targets for enteric bacteria-derived toxins.

The application of a multidisciplinary approach to study bacterial pathogenesis, along with the recent sequencing of entire microbial genomes have made possible discoveries that are changing the way scientists view the bacterium-host interaction. Today, research on the molecular basis of the pathogenesis of infectious diarrheal diseases of necessity transcends established boundaries between microbiology, cell biology, intestinal pathophysiology, and immunology. Novel multidisciplinary approaches led to the discovery of new bacteria-host cell interactions involving signals regulating intestinal permeability through the modulation of cell cytoskeleton and intercellular tight junctions (TJ). A century ago, TJ were conceptualized as a secreted extracellular cement forming an absolute and unregulated barrier within the paracellular space. Biological studies of the past several decades have shown that TJ are dynamic structures subjected to structural changes that dictate their functional status under a variety of developmental, physiological, and pathological circumstances. To meet the many diverse physiological challenges to which the intestinal epithelial barrier is subjected, TJ must be capable of rapid and coordinated responses. This requires the presence of a complex regulatory system that orchestrates the state of assembly of the TJ multiprotein network. Many pathogenic bacteria exploit this system to accomplish their pathogenic strategies by ultimately modulating intestinal permeability.

Animals↗

Evolutionary dynamics of invasion and escape.

Whenever life wants to invade a new habitat or escape from a lethal selection pressure, some mutations may be necessary to yield sustainable replication. We imagine situations like (i) a parasite infecting a new host, (ii) a species trying to invade a new ecological niche, (iii) cancer cells escaping from chemotherapy, (iv) viruses or microbes evading anti-microbial therapy, and also (v) the repeated attempts of combinatorial chemistry in the very beginning of life to produce self-replicating molecules. All such seemingly unrelated situations have a common structure in terms of Darwinian dynamics: a replicator with a basic reproductive ratio less than one attempts to find some mutations that allow indefinite survival. We develop a general theory, based on multitype branching processes, to describe the evolutionary dynamics of invasion and escape.

Animals↗

Toxins and the gut: role in human disease.

Bacterial enteric infections exact a heavy toll on the human population, particularly among children. Despite the explosion of knowledge on the pathogenesis of enteric diseases experienced during the past decade, the number of diarrhoeal episodes and human deaths reported worldwide remains of apocalyptic dimensions. However, our better understanding of the pathogenic mechanisms involved in the onset of diarrhoea is finally leading to preventive interventions, such as the development of enteric vaccines, that may have a significant impact on the magnitude of this human plague. The application of a multidisciplinary approach to study bacterial pathogenesis, along with the recent sequencing of entire microbial genomes, have made possible discoveries that are changing the way scientists view the bacterium-host interaction. Today, research on the molecular basis of the pathogenesis of infective diarrhoeal diseases of necessity transcends established boundaries between microbiology, cell biology, intestinal pathophysiology, and immunology. This review focuses on the most recent outcomes of this multidisciplinary effort.

Actins↗

Opsonin-independent adherence and intracellular development of Legionella pneumophila within U-937 cells.

Legionella pneumophila adhered to and multiplied intracellularly in the human histiocytic lymphoma U-937 cell line. The infectious process was evaluated by viable bacterial cell colony counts and documented by transmission and scanning electron microscopy. In the absence of opsonins, wash-resistant bacterial adherence to host cells occurred within 1 h and attachment of 1 or 2 organisms per U-937 host cell involved close surface interactions at the prokaryotic and eukaryotic membranes. Intracellular multiplication of bacteria was maximal by 24 h after inoculation of cell monolayers. Release of L. pneumophila from these cells appeared as a lytic process that resulted in an increase in the numbers of microorganisms in the extracellular fluids and a concomitant decline in the number of intracellular bacteria. The course of cellular infection was completed by 72 h. The cellular and ultrastructural events of L. pneumophila adherence and uptake by U-937 cells in the absence of antibody or complement have been defined. In addition, this work further establishes the U-937 cell as a suitable model for investigating Legionella--host cell interactions.

Bacterial Adhesion↗

Exploring host-pathogen interactions at the epithelial surface: application of transcriptomics in lung biology.

The epithelial surface of the airways is the largest barrier-forming interface between the human body and the outside world. It is now well recognized that, at this strategic position, airway epithelial cells play an eminent role in host defense by recognizing and responding to microbial exposure. Conversely, inhaled microorganisms also respond to contact with epithelial cells. Our understanding of this cross talk is limited, requiring sophisticated experimental approaches to analyze these complex interactions. High-throughput technologies, such as DNA microarray analysis and serial analysis of gene expression (SAGE), have been developed to screen for gene expression levels at large scale within single experiments. Since their introduction, these hypothesis-generating technologies have been widely used in diverse areas such as oncology and brain research. Successful application of these genomics-based technologies has also revealed novel insights in host-pathogen interactions in both the host and pathogen. This review aims to provide an overview of the SAGE and microarray technology illustrated by their application in the analysis of host-pathogen interactions. In particular, the interactions between epithelial cells in the human lungs and clinically relevant microorganisms are the central focus of this review.

Epithelial Cells↗

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↗

Viral peptide specific cytotoxic T lymphocytes are of high avidity to host-MHC but only low avidity to donor-MHC after allogeneic bone marrow transplantation.

In the thymus maturing T lymphocytes are positively selected for efficient interaction with self-MHC molecules. Consequently, mature peripheral T cells recognize foreign (microbial) antigens in association with self-MHC molecules (known as MHC restricted recognition). In experimental bone marrow transplantation (BMT) lymphohaemopoietic stem cells from an MHC disparate donor transfused to an irradiated host give rise to mature T lymphocytes with host-MHC restriction specificity. While experiments with T cell receptor transgenic mice have largely confirmed this concept, many studies using genetically unmanipulated animals analysing polyclonal T cell repertoires have also shown donor-MHC restricted T cell activities after allogeneic BMT. To analyse this discrepancy we generated 18 virus specific cytotoxic T cell (CTL) clones, 16 from F1 into parent and two from fully allogeneic bone marrow chimeras, and analysed the MHC restriction specificity in proliferation and cytotoxicity assays. The cytotoxicity of all the clones was primarily host-MHC restricted. However, the CTL clones proliferated to viral antigen presented by both donor- or host-MHC. Our model allowed CTL cloning by cross-specific stimulation with antigen plus either donor-MHC or else host-MHC. Interestingly, even the 14 CTL clones which had been raised with donor-MHC systematically killed host-MHC but not donor-MHC expressing cells. Thus, after BMT, CTLs may proliferate crossreactively to donor-MHC but cytolysis is predominantly directed to host-MHC expressing cells. Since lytic CTL activity probably reflects high avidity CTL interaction necessary for viral clearance in vivo, the data suggest that the donor-MHC restricted CTL activity may not be protective and that virus may escape CTL surveillance in donor cells.

Animals↗

Regulation of the immunostimulatory activity of rat pulmonary interstitial dendritic cells by cell-cell interactions and cytokines.

Pulmonary dendritic cells (DC) are potent antigen-presenting cells that are thought to play a critical role in the initiation of immune responses within the lung. Because the lung is both a site of entry into the body for microbial pathogens and the organ of gas exchange, pulmonary immune responses must be meticulously regulated to achieve a balance between host defense and respiration. The initial interaction of DC with T cells in the lung is an excellent point at which to control local immune responses. Studies of the regulation of DC accessory cell function have been greatly hampered by difficulties in obtaining pure populations of pulmonary DC that have not been subjected to prolonged incubations during which the DC may undergo functional alteration. We now describe a method for isolating pulmonary DC from the rat that yields 1 x 10(5) cells/rat with > 90% purity. These cells are potent accessory cells, inducing T cell proliferation in a mixed leukocyte reaction (MLR) at a stimulator-to-responder ratio of 1:1,000. This method, which involves flow cytometric separation of nonphagocytic cells that stain brightly for class II MHC (OX6) from a population of low-density pulmonary interstitial cells, avoids extended incubations at 37 degrees C and thus allows study of a relatively pure population of cells that have functional capacities resembling those of naive cells from the normal lung. With these cells, we demonstrate that the functional capacity of pulmonary DC as stimulator cells in an MLR is significantly increased by exposure to the cytokines interleukin-1 or granulocyte/macrophage colony-stimulating factor (GM-CSF) and by culture with interstitial, but not alveolar, macrophages. Furthermore, DC are heterogeneous with respect to the cell surface expression of receptor for GM-CSF, and this expression is subject to modulation in cell culture. From these studies, we conclude that the immunostimulatory capacity of pulmonary DC is a function of local interactions with cytokines and other parenchymal cells. This suggests that DC function may be an important regulatory point for the local control of pulmonary immune responses.

Animals↗

Commensal bacteria make a difference.

Nowhere is the relationship between microorganisms and eukaryotes as diverse, intimate and clinically relevant as in the gastrointestinal tract. An estimated 500-1000 mostly anaerobic species reside in the intestine, approaching enormous densities of 10(11)-10(12) organisms per gram colon content. The commensal interactions between intestinal microorganisms and animal hosts have been difficult to study in the past because of the diversity of microorganisms involved and because of the lack of culturability that accompanies many microbial consortia. However, recent work has provided new insights into these interactions.

Anaerobiosis↗

The mouse gut microbiota responds to predator odor and predicts host behavior.

Chronic stressors can alter the mammalian gut microbiota in ways that mediate host stress responses, but the impacts of acute stressors on these interactions are less well understood. Here, we show that brief exposure of wild-derived mice to predator odor altered gut-microbiota composition, which in turn predicted host behavior. We investigated the individual and combined effects of 15-minute exposures to synthetic fox fecal odor and 30 days of chronic social isolation, an established chronic stressor. Using ethological assays, visceral adipose tissue transcriptomics, and genome-resolved metagenomics, we found that predator-odor exposure significantly affected mouse behavior, gene expression, and gut microbiota. Predator odor-responsive bacteria were associated with the expression of genes involved in anti-microbial defense, and host behavioral responses were predicted by random forest models trained on gut-microbiota profiles. These findings indicate interactions between the gut microbiota and wild-mouse responses to the threat of predation, an ecologically relevant acute stressor.

Journal Article↗

[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↗

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↗