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PubMed2004

Infections due to emerging and uncommon medically important fungal pathogens.

The emergence of less common but medically important fungal pathogens contributes to the rate of morbidity and mortality, especially in the increasingly expanding population of immunocompromised patients. These pathogens include septate filamentous fungi (e.g., Fusarium spp., Scedosporium spp., Trichoderma spp.), nonseptate Zygomycetes, the endemic dimorphic pathogen Penicillium marneffei, and non-Cryptococcus, non-Candida pathogenic yeast (e.g., Trichosporon spp.). The medical community is thus called upon to acquire an understanding of the microbiology, epidemiology and pathogenesis of these previously uncommon pathogens in order to become familiar with the options for prevention and treatment.

Humans↗
PubMed2006

Effect of Lactobacillus isolates on the adhesion of pathogens to chicken intestinal mucus in vitro.

AIMS: The aims of this study were to investigate in vitro the effects of Lactobacillus isolates from a chicken on adhesion of pathogenic Salmonella and Escherichia coli to chicken intestinal mucus obtained from different intestinal regions. METHODS AND RESULTS: Bacteria were labelled by using methyl-1,2-[(3)H]-thymidine. The bacterial adhesion was assessed by measuring the radioactivity of bacteria adhered to the mucus. The results showed that the abilities of Lactobacillus spp. to bind to the same intestinal mucus were higher than those of pathogenic Salmonella and E. coli. Pretreatment of intestinal mucus with Lactobacillus fermentum and Lactobacillus acidophilus, alone or in combination, reduced the adhesion of the tested pathogens, but the reductive extent of pathogenic adhesion by Lactobacillus spp. in combination was relatively high. CONCLUSIONS: The tested bacteria had different adhesions to mucus glycoproteins isolated from different intestinal regions of chicken. Lactobacillus acidophilus and Lact. fermentum in combination revealed a better ability to inhibit attachments of Salmonella and E. coli to chicken intestinal mucus than Lactobacillus sp. alone. SIGNIFICANCE AND IMPACT OF THE STUDY: A mixture of intestinal Lactobacillus spp. from a chicken may play a protective role in excluding pathogenic Salmonella and E. coli from the intestine of chicken.

Animals↗
PubMed2006

Trade-offs between longevity and pathogen resistance in Drosophila melanogaster are mediated by NFkappaB signaling.

The innate immune response protects numerous organisms, including humans, from the universe of pathogenic molecules, viruses and micro-organisms. Despite its role in promoting pathogen resistance, inappropriate activation and expression of NFkappaB and other immunity-related effector molecules can lead to cancer, inflammation, and other diseases of aging. Understanding the mechanisms leading to immune system activation as well as the short- and long-term consequences of such activation on health and lifespan is therefore critical for the development of beneficial immuno-modulating and longevity-promoting interventions. Mechanisms of innate immunity are highly conserved across species, and we take advantage of genetic tools in the model organism, Drosophila melanogaster, to study the effects of acute and chronic activation of immunity pathways on pathogen resistance and general fitness of adult flies. Our findings indicate that fat body specific overexpression of a putative pathogen recognition molecule, peptidoglycan recognition protein (PGRP-LE), is sufficient for constitutive up-regulation of the immune response and for enhanced pathogen resistance. Primary components of fitness are unaffected by acute activation, but chronic activation leads to an inflammatory state and reduced lifespan. These phenotypes are dependent on the NFkappaB-related transcriptional factor, Relish, and they establish a mechanistic basis for a link between immunity, inflammation, and longevity.

Animals↗
PubMed2006

Pathogenic colonization of the stomach in enterally fed elderly patients: Comparing percutaneous endoscopic gastrostomy with nasogastric tube.

OBJECTIVES: To compare the gastric juice microbiota of older people fed through a percutaneous endoscopic gastrostomy tube (PEG) with that of those fed through a nasogastric tube (NGT). DESIGN: Prospective comparative study. SETTING: Nursing and skilled nursing wards. PARTICIPANTS: Fifty-four elderly PEG-fed and 52 NGT-fed patients. MEASUREMENTS: Cultures from the oropharynx and the gastric juice. RESULTS: Pathogenic bacteria were isolated from the oropharynxes of 44% of the PEG-fed patients and 54% of the NGT-fed patients. The most frequent gram-negative bacilli isolated from the oropharynx were Proteus spp. (13-21%) and Pseudomonas aeruginosa (13-18%), with no significant difference between the groups. Isolation rates from the gastric juice were significantly more frequent in the NGT-fed patients than in the PEG-fed patients for Proteus spp. (4% vs 23%), Escherichia coli (6% vs 21%), and mixed flora (11% vs 27%). Significant correlation was found between high gastric pH and the isolation of bacteria in both groups (correlation coefficient = 0.58, P < .001). CONCLUSION: Gastric juice of PEG-fed patients harbors pathogenic bacteria in significant numbers. No significant difference was noted with respect to the rate of isolation of pathogenic bacteria from the oropharynx between the groups. Major bacterial pathogens, such as P. aeruginosa and Proteus spp., were isolated significantly more from the gastric juice of NGT-fed patients. These results support the view that a bidirectional spread pattern of pathogens may take place in NGT-fed patients.

Aged↗
PubMed2006

Environmental survey for four pathogenic bacteria and closely related species using phylogenetic and functional genes.

Bacterial species with high DNA sequence similarity to pathogens could affect the specificity of assays designed to detect biological threat agents in environmental samples. The natural presence of four pathogenic bacteria, Bacillus anthracis, Clostridium perfringens, Francisella tularensis, and Yersinia pestis and their closely related species, was determined for a large collection of soil and aerosol samples. Polymerase chain reaction (PCR) and gene sequencing were used using group-specific 16S rRNA primers to identify pathogens and related species, and pathogen-specific virulence genes. Close relatives of B. anthracis (B. cereus group species) were detected in 37% of the soils and 25% of the aerosol samples. The B. anthracis protective antigen (pag) gene or a close homolog was detected in 16 of these samples. For the other three pathogen groups, the frequency of detection was much lower, and none of the samples were positive with both the phylogenetic and virulence gene primer sets.

Aerosols↗
PubMed2006

Molecular organization of the cell wall of Candida albicans and its relation to pathogenicity.

Candida albicans is one of the most important opportunistic pathogenic fungi. Weakening of the defense mechanisms of the host, and the ability of the microorganism to adapt to the environment prevailing in the host tissues, turn the fungus from a rather harmless saprophyte into an aggressive pathogen. The disease, candidiasis, ranges from light superficial infections to deep processes that endanger the life of the patient. In the establishment of the pathogenic process, the cell wall of C. albicans (as in other pathogenic fungi) plays an important role. It is the outer structure that protects the fungus from the host defense mechanisms and initiates the direct contact with the host cells by adhering to their surface. The wall also contains important antigens and other compounds that affect the homeostatic equilibrium of the host in favor of the parasite. In this review, we discuss our present knowledge of the structure of the cell wall of C. albicans, the synthesis of its different components, and the mechanisms involved in their organization to give rise to a coherent composite. Furthermore, special emphasis has been placed on two further aspects: how the composition and structure of C. albicans cell wall compare with those from other fungi, and establishing the role of some specific wall components in pathogenesis. From the data presented here, it becomes clear that the composition, structure and synthesis of the cell wall of C. albicans display both subtle and important differences with the wall of different saprophytic fungi, and that some of these differences are of utmost importance for its pathogenic behavior.

Animals↗
PubMed2000

Comparison of conventional and molecular methods for the detection of bacterial pathogens in sputum samples from cystic fibrosis patients.

The nature of the micro-flora present in sputa of six different cystic fibrosis (CF) patients was assessed using routine microbiological culture and molecular methods. Bacterial genes for the small subunit ribosomal RNA (ssu rDNA) were specifically amplified from DNA extracted from the sputum samples, cloned and characterised by hybridisation and DNA sequencing. A large number of clones from six sputa were screened. Initially, oligonucleotide hybridisation was performed with five probes, specific for Gram-positives and Gram-negatives in general and the main pathogens for the CF patient (Staphylococcus aureus, Pseudomonas aeruginosa and Haemophilus influenzae). For a single sputum sample, the results were fully congruent when culture and molecular methods were compared. In the other five sputa, discrepancies for S. aureus and/or H. influenzae were documented. Although S. aureus DNA and H. influenzae DNA was detected in three and four sputa, respectively, strains could not be cultured. Although the PCR approach is not capable of distinguishing viable from dead bacteria, all of the CF patients had a history of S. aureus infections, while one of the CF patients once had cultivable H. influenzae in the sputum as well. A number of clones for probe-unidentified Gram-negative or Gram-positive bacterial species were further analysed by sequencing and additional potential pathogens were identified. Although routine culture of sputum frequently points to mono-specific exacerbations, our molecular data indicate that the other CF-related pathogens appear to be persistently present as well. We conclude that routine culture for bacterial pathogens from CF sputa yields limited microbiological information since it frequently fails to identify a number of pathogenic bacterial species that are potentially present in a viable status in the lungs of these patients.

Adult↗
PubMed1993

Signal transduction and virulence regulation in human and animal pathogens.

Pathogens have developed many strategies for survival in animals and humans which possess very effective defense mechanisms. Although there are many different ways, in which pathogenic bacteria solved the problem to overcome the host defense, some common features of virulence mechanisms can be detected even in phylogenetically very distant bacteria (Finlay and Falkow (1989) Microb. Rev. 6, 1375-1383). One important feature is that the regulation of expression of virulence factors and the exact timing of their expression is very important for many of the pathogenic bacteria, as most of them have to encounter different growth situations during an infection cycle, which require a fast adaptation to the new situation by the expression of different factors. This review gives an overview about the mechanisms used by pathogenic bacteria to accomplish the difficult task of regulation of their virulence potential in response to environmental changes. In addition, the relationship of these virulence regulatory systems with other signal transduction mechanisms not involved in pathogenicity is discussed.

Animals↗
PubMed2006

Developing insect models for the study of current and emerging human pathogens.

The study of human diseases requires the testing of microorganisms in model systems. Although mammals are typically used, we argue the validity of using insects as models in order to examine human diseases, particularly the growing number of opportunistic microorganisms. Insects can be used in large numbers, are easily manipulated, and are not subject to the same ethical concerns as mammalian systems. Insects and mammals have many parallels with respect to microbial pathogenesis, from proteinaceous integuments that require breaching before infection to similarities in their innate immune responses. Reactions of insects to Candida and Pseudomonas spp. infections show good correlation with mouse models, providing precedent-setting examples of the study of human pathogens using insects. Insects as pathogen hosts also warrant study because they may act as reservoirs for emerging human pathogens. Finally, insect models may be used to examine the evolutionary processes involved in the acquisition of virulence factors and host-jumping mechanisms indispensable to emerging pathogens. Insect models may be used in 'niche' investigations where large sample sizes can facilitate rapid, informative screening of opportunistic diseases and provide insights into pathogen evolution, while reducing the cost and ethical concerns associated with mammalian models.

Animals↗
PubMed2007

Activation of quiescent infections by postharvest pathogens during transition from the biotrophic to the necrotrophic stage.

Insidious fungal infections of postharvest pathogens remain quiescent, as biotrophs, during fruit growth and harvest, but activate their development and transform to necrotrophs, which elicit decay symptoms, during ripening and senescence. Exposure of unripe hosts to pathogens quickly initiates defensive signal-transduction cascades that limit fungal growth and development, but exposure to the same pathogens during ripening and storage activates a substantially different signaling cascade that facilitates fungal colonization. The first step in the activation of quiescent infections may involve the fungal capability to cope with plant defense responses by detoxification and efflux transport of antifungals, or by overcoming the suppression of pathogenicity factors. The second step toward the activation of quiescent infections is actively modulated by the pathogen in response to a host signal(s), and includes alkalization or ammonification of the host tissue, which sensitizes the host and activates the transcription and secretion of fungal-degradative enzymes that promote maceration of the host tissue. Feedback signals involving, for example, nitrogen and sugar further enhance pH changes, synthesis of hydrolytic enzymes and saprophytic development in the macerated tissue. This review describes the coordinated series of mechanisms that regulate the activation of quiescent infections in various fruit/vegetable-pathogen interactions.

Fruit↗
PubMed1994

Genetic approaches to study Legionella pneumophila pathogenicity.

Legionella pneumophila is an intracellular pathogen replicating in human macrophages during the course of infection of the lungs. Infection by legionellae often leads to severe pneumonia, termed Legionnaires' disease. Genetic approaches to identify the factors responsible for L. pneumophila pathogenicity started with the construction of genomic libraries in Escherichia coli. Various L. pneumophila-specific genes were cloned in E. coli K-12 by identification using functional assays, antibody screening and hybridization ('reverse genetics'). By disrupting the genes via allelic exchange, mutants have been created to assess the influence of the factors on pathogenicity. Among the cloned genes, only for the gene product of the mip gene, encoding a 24-kDa surface-associated protein (macrophage infectivity potentiator) unequivocal evidence for its contribution to pathogenicity could be provided. Two hemolytic factors that have been cloned do not seem to play a role in L. pneumophila pathogenicity. Genetic systems for transposon mutagenesis of the L. pneumophila genome (Tn5, Tn903dIIlacZ, MudphoA), including Tn phoA shuttle mutagenesis, have been established and specifically adapted to identify mutants which displayed an impaired capability to multiply inside macrophages and with a reduced in vivo virulence. Furthermore, by complementation of avirulent mutants, genetic loci could be identified which restored the virulence.

Gene Expression Regulation, Bacterial↗
PubMed1995

Pathogen-based models favoring MHC genetic diversity.

We present six models that are currently the most likely ways that pathogens might favor the evolution of MHC genetic diversity. Although each model makes one or more unique predictions, the current lack of crucial data prevents distinguishing the relative importance of each model. However, this first-time organization of these models should contribute to the design of critical experiments. This synthetic review yields at least three essentially new ideas. First, MHC-dependent immune recognition may be sufficiently redundant to render it essentially escape-proof by pathogens. Second, the four models based on pathogen escape do not work (or work weakly) for diversifying class II genes, unless class II-restricted cytotoxic T-cells are important, an idea that is controversial. Third, pathogen-escape events have traditionally been thought to result in only frequency-dependent selection but here we show that heterozygote advantage is an inevitable consequence of such pathogen evasion. Therefore, the controversy over the relative importance of these two forms of balancing selection is largely a false dichotomy.

Animals↗
PubMed1999

Human pathogen subversion of antigen presentation.

Many pathogens have co-evolved with their human hosts to develop strategies for immune evasion that involve disruption of the intracellular pathways by which antigens are bound by class I and class II molecules of the major histocompatibility complex (MHC) for presentation to T cells. Here the molecular events in these pathways are reviewed and pathogen interference is documented for viruses, extracellular and intracellular bacteria and intracellular parasites. In addition to a general review, data from our studies of adenovirus, Chlamydia trachomatis and Coxiella burnetii are summarized. Adenovirus E19 is the first viral gene product described that affects class I MHC molecule expression by two separate mechanisms, intracellular retention of the class I heavy chain by direct binding and by binding to the TAP transporter involved in class I peptide loading. Coxiella and Chlamydia both affect peptide presentation by class II MHC molecules as a result of their residence in endocytic compartments, although the properties of the parasitophorous vacuoles they form are quite different. These examples of active interference with antigen presentation by viral gene products and passive interference by rickettsiae and bacteria are typical of the strategies used by these different classes of pathogens, which need to evade different types of immune responses. Pathogen-host co-evolution is evident in these subversion tactics for which the pathogen crime seems tailored to fit the immune system punishment.

Animals↗
PubMed1991

The prevalence of enteric pathogens in diarrhoeic thoroughbred foals in Britain and Ireland.

A survey of 77 normal and 326 diarrhoeic foals in Britain and Ireland from 1987 to 1989 revealed a significantly higher prevalence of Group A rotaviruses and Aeromonas hydrophila in diarrhoeic foals. The prevalence of cryptosporidia, potentially pathogenic Escherichia coli, Yersinia enterocolitica and Clostridium perfringens was similar in normal or diarrhoeic foals. Rotaviruses had a similar prevalence in all age groups of scouring foals up to three months of age, with an overall prevalence of 37 per cent among diarrhoeic foals. The number of cases of diarrhoea varied considerably from year to year, but in all three years of the survey rotavirus was a significant pathogen. A comparison of diagnostic tests for rotavirus in the faeces showed electron microscopy (EM) and polyacrylamide gel electrophoresis (PAGE) to have similar sensitivity. The Rotazyme ELISA test kit was found to have the same sensitivity as a combination of EM and PAGE. A. hydrophila had an overall prevalence of 9 per cent among diarrhoeic foals, although its prevalence was higher in some age groups. A. hydrophila has not been established previously as a significant enteric pathogen in foals. Other putative pathogens found at very low prevalence were coronavirus, the putative picobirnavirus, Campylobacter spp. and Salmonella spp. No evidence was found of synergistic effects between rotavirus, cryptosporidia and potentially pathogenic E. coli. Neither coccidia nor non-Group A rotaviruses were found in any of the samples examined.

Aeromonas↗
PubMed1995

[Study of pathogenicity of various serovars of Enterococcus faecalis].

Using a mouse experimental UTI (urinary tract infection) model, a study was conducted to find the pathogenicity of various serovars of E. faecalis. On the basis of studies employing serovar-specific factor sera prepared with E. faecalis type strains, serovar 2, 3, 4 and 10 strains showed a high incidence of involvement in pyelonephritis: 90.3%, 85.7%, 85% and 73.3%. Serovar 1, 6 and 7 strains each showed a 63.6% incidence of involvement in pyelonephritis, indicating that they have a moderate pathogenicity. The pathogenicity of the other serovar strains was not very strong, with a low incidence of 40-59.1%. These results were thus in good agreement with the findings of the study using the mouse experimental UTI model infected with clinical isolates. Serotyping was performed of E. faecalis clinical isolates obtained from patients with pyelonephritis or urosepsis. Serovars 2 and 4 comprised 75.1% of these isolates. It was surmised that E. faecalis serovars 2 and 4 tend to have strong pathogenicity. Thus, there were quite a few differences in pathogenicity of E. faecalis according to each kind of serovar.

Animals↗
PubMed1998

[A clinical study of respiratory infection isolating non-pathogenic Neisseria by transtracheal aspiration].

Neisseria species other than N. meningitidis and N. gonorrhoeae are generally regarded as commensal bacterial flora of the oropharynx, and little is known regarding cases of these non-pathogenic Neisseria species in the lower respiratory tract. We clinically examined respiratory tract infections from which non-pathogenic Neisseria species were isolated by transtracheal aspiration (TTA). The incidence of non-pathogenic Neisseria isolated was 54 (15.7%) out of 344 episodes of respiratory tract infections with isolated microorganisms from TTA, and was 17.6%, 15.8%, 14.3% for pneumonia, acute bronchitis, and chronic lower respiratory tract infection, respectively. All 54 episodes were isolated with other microorganisms such as alpha-Streptococcus spp. (75.9%), Haemophilus influenzae (25.9%) and anaerobics (22.2%). The isolation ratio according to the age group increased at 45 years of age or more, but did not increase with the advance of age. Predisposing factors were identified such as overt aspiration, iatrogenic procedure and heavy smoking. Cases without overt aspiration that had fevers of 38 degrees C or more or hypoxemia of less than PaO2 70 torr when detecting non-pathogenic Neisseria were observed more frequently in the aged than the non-aged. The findings suggest the detection of non-pathogenic Neisseria by TTA is influenced by the host state that the fall of microorganisms from the upper to lower respiratory tract cannot be defended or excluded by mucociliary transportation disorder due to underlying disease and smoking, or deterioration of physical status other than overt or silent aspiration.

Age Factors↗
PubMed2001

Population biology of multihost pathogens.

The majority of pathogens, including many of medical and veterinary importance, can infect more than one species of host. Population biology has yet to explain why perceived evolutionary advantages of pathogen specialization are, in practice, outweighed by those of generalization. Factors that predispose pathogens to generalism include high levels of genetic diversity and abundant opportunities for cross-species transmission, and the taxonomic distributions of generalists and specialists appear to reflect these factors. Generalism also has consequences for the evolution of virulence and for pathogen epidemiology, making both much less predictable. The evolutionary advantages and disadvantages of generalism are so finely balanced that even closely related pathogens can have very different host range sizes.

Animals↗
PubMed2001

The plasticity of dendritic cell responses to pathogens and their components.

Dendritic cells are involved in the initiation of both innate and adaptive immunity. To systematically explore how dendritic cells modulate the immune system in response to different pathogens, we used oligonucleotide microarrays to measure gene expression profiles of dendritic cells in response to Escherichia coli, Candida albicans, and influenza virus as well as to their molecular components. Both a shared core response and pathogen-specific programs of gene expression were observed upon exposure to each of these pathogens. These results reveal that dendritic cells sense diverse pathogens and elicit tailored pathogen-specific immune responses.

Antigen Presentation↗