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Immunity and tolerance to Aspergillus involve functionally distinct regulatory T cells and tryptophan catabolism.

The inherent resistance to diseases caused by Aspergillus fumigatus suggests the occurrence of regulatory mechanisms that provide the host with adequate defense without necessarily eliminating the fungus or causing unacceptable levels of host damage. In this study, we show that a division of labor occurs between functionally distinct regulatory T cells (Treg) that are coordinately activated by a CD28/B-7-dependent costimulatory pathway after exposure of mice to Aspergillus conidia. Early in infection, inflammation is controlled by the expansion, activation and local recruitment of CD4+CD25+ Treg capable of suppressing neutrophils through the combined actions of IL-10 and CTLA-4 on indoleamine 2,3-dioxygenase. The levels of IFN-gamma produced in this early phase set the subsequent adaptive stage by conditioning the indoleamine 2,3-dioxygenase-dependent tolerogenic program of dendritic cells and the subsequent activation and expansion of tolerogenic Treg, which produce IL-10 and TGF-beta, inhibit Th2 cells, and prevent allergy to the fungus. The coordinate activation of Treg may, however, be subverted by the fungus, as germinating conidia are capable of interfering with anti-inflammatory and tolerogenic Treg programs. Thus, regulation is an essential component of the host response in infection and allergy to the fungus, and its manipulation may allow the pathogen to overcome host resistance and promote disease.

Animals↗

Natural selection on floral traits of female Silene dioica by a sexually transmitted disease.

Floral traits endowing high reproductive fitness can also affect the probability of plants contracting sexually transmitted diseases. We explore how variations in floral traits influence the fitness of Silene dioica females in their interactions with pollinators carrying pollen or spores of the sterilizing anther-smut fungus Microbotryum violaceum. We collected healthy and infected plants in a highly diseased population and grew them under conditions that 'cure' infected individuals, and used standard regression methods to detect natural selection on floral traits. Narrow-sense heritabilities, coefficients of additive genetic variation (CV(A)) and genetic correlations among traits were estimated from paternal half-sib groups. Pollinator preferences imposed strong direct and directional selection on traits affecting female attractiveness and pollen-/spore-capturing abilities. Levels of additive genetic variance were high in these traits, suggesting that rapid responses to selection are possible. By considering our results in the light of spatial and temporal heterogeneity resulting from the colonization dynamics typical for this species, we suggest that the conflicting selective effects of pollen/spore loads lead to the maintenance of genetic variation in these traits.

Flowers↗

Fusicoccum arbuti sp. nov. causing cankers on pacific madrone in western North America with notes on Fusicoccum dimidiatum, the correct name for Scytalidium dimidiatum and Nattrassia mangiferae.

Pacific madrone (Arbutus menziesii) is a broadleaf evergreen tree native to western North America that has been in decline for the past 30 years. A fungus has been isolated and was verified as the cause of cankers on dying trees. It was determined to belong in the genus Fusicoccum, an asexual state of Botryosphaeria. This genus in both its sexual and asexual states commonly causes canker diseases of deciduous woody plants. Using morphological and molecular data the fungus causing cankers on Pacific madrone is characterized, described and illustrated as a new species of Fusicoccum, F. arbuti D.F. Farr & M. Elliott sp. nov. No sexual state is known for F. arbuti. Evidence from the literature, cultures and specimens suggests that F. arbuti, often mistakenly identified as Nattrassia mangiferae, has been causing madrone canker since at least 1968. Authentic isolates of Nattrassia mangiferae as the synanamorph Scytalidium dimidiatum were sequenced and determined to be different from Fusicoccum arbuti and to belong in Botryosphaeria/Fusicoccum. In addition to molecular sequence data, the morphology of the pycnidial and arthric conidial states of Nattrassia mangiferae/ Scytalidium dimidiatum resembles that of Fusicoccum. Therefore the correct name for Nattrassia mangiferae and its numerous synonyms (Dothiorella mangiferae, Torula dimidata, Scytilidium dimidiatum, Fusicoccum eucalypti, Hendersonula toruloidea, H. cypria, Exosporina fawcetii, H. agathidia, and S. lignicola) is Fusicoccum dimidiatum (Penz.) D.F. Farr, comb. nov.

Ascomycota↗

Phylogenetic and evolutionary aspects of Paracoccidioides brasiliensis reveal a long coexistence with animal hosts that explain several biological features of the pathogen.

The habitat of the mycelial saprobic form of Paracoccidioides brasiliensis, which produces the infectious propagula, has not been determined and has proven difficult for mycologists to describe. The fungus has been rarely isolated from the environment, the disease has a prolonged latency period and no outbreaks have been reported. These facts have precluded the adoption of preventive measures to avoid infection. The confirmation of natural infections in nine-banded armadillos (Dasypus novemcinctus) with P. brasiliensis, in high frequency and wide geographic distribution, has opened new avenues for the study and understanding of its ecology. Armadillos belong to the order Xenarthra, which has existed in South America ever since the Paleocene Era (65 million years ago), when the South American subcontinent was still a detached land, before the consolidation of what is now known as the American continent. On the other hand, strong molecular evidence suggests that P. brasiliensis and other dimorphic pathogenic fungi--such as Blastomyces dermatitidis, Coccidioides immitis and Histoplasma capsulatum--belong to the family Onygenaceae sensu lato (order Onygenales, Ascomycota), which appeared around 150 million years ago. P. brasiliensis ecology and relation to its human host are probably linked to the fungal evolutionary past, especially its long coexistence with and adaptation to animal hosts other than Homo sapiens, of earlier origin. Instead of being a blind alley, the meaning of parasitism for dimorphic pathogenic fungi should be considered as an open two-way avenue, in which the fungus may return to the environment, therefore contributing to preserve its teleomorphic (sexual) and anamorphic (asexual) forms in a defined and protected natural habitat.

Animals↗

Pneumocystis carinii: an atypical fungal micro-organism.

The purpose of this review is to assist mycologists in having a better understanding of Pneumocystis carinii and the disease that it causes. Now considered to be a fungus, P. carinii is unusual in its life cycle and relationship with the host. P. carinii pneumonia (PCP) pathogenesis, immunology and host defence mechanisms are examined, as well as epidemiological and control strategies. Most pneumocystosis pathophysiological changes result from the parasite's attachment and proliferation in the lungs, resulting in a filling of the alveoli with masses of the micro-organism. Pathological changes include an increase in alveolar capillary membrane permeability and injury to the alveolar epithelium, which may be mediated by the release of degradative enzymes from the pathogen. A host response takes place by hypertrophy, and hyperplasia involving type II epithelial alveolar cells. P carinii interacts with pulmonary surfactants by binding to the hydrophilic proteins A and D, and by modifying their phospholipid composition. Alveolar macrophages and CD4+ T cells play a key role in the host's defence against Pneumocystis. The epidemiology of PCP remains poorly understood. Airborne transmission has been established, but the actual infective form and its source remains unknown. Studies concerning P. carinii genetic diversity have shown that the parasite polymorphism is related, at least partially, to the host species. A strong host-species specificity in P. carinii has been found. From an epidemiological perspective, there appears to be no animal reservoir for the agent of human PCP. Thus, this disease should not be considered to be zoonotic. Although a significant decrease in the incidence of pneumocystosis has been obtained when employing chemoprophylaxis, anti-P. carinii drugs are not completely successful, often inducing deleterious side-effects. For these reasons, new prophylactic and therapeutic strategies need to be developed. One approach could be based on the anti-P. carinii effect of yeast killer toxins and antibiotic anti-idiotypic antibodies.

Animals↗

Acute rhinocerebral mucormycosis caused by Rhizopus arrhizus from Sri Lanka.

Rhinocerebral mucormycosis is a rare fungus infection reported mainly from the United States of America and Europe. The disease is caused by zygomycete fungi, most often by a Rhizopus species. Diagnosis is often made post-mortem and in many instances culture identification of the fungus responsible has not been performed. A case of culturally proven rhinocerebral mucormycosis is described for the first time in Sri Lanka. The patient was a 56-year-old male who had been treated for diabetes mellitus for 17 years. He had typical symptoms of numbness and loss of sensations over the temporal region, followed by loss of vision and proptosis, all on the right side of his face. The diagnosis of rhinocerebral mucormycosis was confirmed by microscopic examination and culture of material obtained from the retro-orbital space. The patient died before effective antifungal therapy could be instituted.

Acute Disease↗

MS-222 (tricaine methane sulfonate) does not kill the amphibian chytrid fungus Batrachochytrium dendrobatidis.

MS-222 (tricaine methane sulfonate) is an agent commonly used to anaesthetise or euthanize amphibians used in experiments. It is administered by immersing the animal to allow absorption through the skin. Chytridiomycosis is an important disease of amphibians and research involves experiments with live animals. Batrachochytrium dendrobatidis, the fungus which causes chytridiomycosis, is located in the skin and therefore the organism should come into contact with MS-222 when it is used. B. dendrobatidis is a sensitive organism which could possibly be killed by MS-222. Hence, results of chytridiomycosis studies in which MS-222 is used could be unreliable. A concentration of 2 g l(-1) and an exposure duration of 1 h is at the high end of the range at which MS-222 would be most commonly used. Exposure to 2 g l(-1) MS-222 for 1 h does not kill B. dendrobatidis cultures, suggesting that MS-222 is safe to use in chytridiomycosis studies.

Aminobenzoates↗

Histoplasmosis in northwestern Argentina. II: Prevalence of Histoplasmosis capsulati and paracoccidioidomycosis in the population south of Chuscha, Gonzalo and Potrero in the province of Tucuman.

The present work was undertaken to obtain epidemiological data on the extent and distribution of Histoplasma capsulatum var. capsulatum and Paracoccidiodes brasiliensis infections south of the Chuscha, Gonzalo and Potrero areas of Argentina. Skin tests surveys of the human population with histoplasmin and paracoccidioidin were carried out in the permanent population of those localities. The infection index of the population showed that the area south of Chuscha has a high-prevalence of histoplasmosis capsulati. The Gonzalo and Potrero areas, according to their rates of infection also can be considered to have a relatively high prevalence of this disease. The frequency of individuals infected with P. brasiliensis suggests that the level of exposure to this fungus is considerable, especially in Gonzalo where the frequency of infection was 9.23%. The endemic areas of both diseases can be superimposed, as occurs in the northeastern part of Argentina.

Adolescent↗

Entomophthoromycosis due to Conidiobolus.

Entomophthoromycosis due to Conidiobolus coronatus is a granulomatous infection characterized by lesions that originate in the inferior turbinate, spread through ostia and foramina to involve the facial and subcutaneous tissues and paranasal sinuses. The majority of the cases have been described from areas of tropical rainforest in West Africa, agricultural and outdoor workers (aged 20-60 years) being the ones most frequently affected. The fungus is common in soil and decaying vegetation. Infection probably occurs by implantation of the spores of the fungus in nasal mucosa. C. incongruus is a rare agent of the disease, so far known only from two cases with lesions involving the pericardium, mediastinum, lungs, liver, oesophagus and jejunum. C. coronatus is known to cause a clinically similar disease in horses, mules, a dolphin and a chimpanzee. A characteristic histological feature is the presence of thin-walled, broad, often septate hyphae or hyphal fragments with a thick eosinophilic sheath, frequently phagocytosed within giant cells. The fungus is known to produce in vitro several enzymes, e.g., elastase, esterase, collagenase and lipase, which have a possible role in pathogenicity. A concentrated brain heart infusion culture filtrate antigen is useful for immunodiagnosis. Several drugs e.g., potassium iodide, cotrimoxazole, amphotericin B, ketoconazole and itraconazole have been tried with varying success. Investigations on the immunology of disease and the role of proteases and lipases in the pathogenesis of infection is an important area of further research.

Animal Diseases↗

Microsatellite markers for powdery mildew resistance in pea (Pisum sativum L.).

Powdery mildew is a common disease of field pea, Pisum sativum L., and is caused by the ascomycete fungus Erysiphe pisi. It can cause severe damage in areas where pea is cultivated. Today breeders want to develop new pea lines that are resistant to the disease. To make the breeding process more efficient, it is desirable to find genetic markers for use in a marker-assisted selection (MAS) strategy. In this study, microsatellites (SSR) were used to find markers linked to powdery mildew resistance. The resistant pea cultivar '955180' and the susceptible pea cultivar 'Majoret' were crossed and F2 plants were screened with SSR markers, using bulked segregant analysis. A total of 315 SSR markers were screened out of which five showed linkage to the powdery mildew resistance gene. No single marker was considered optimal for inclusion in a MAS program. Instead, two of the markers can be used in combination, which would result in only 1.6% incorrectly identified plants. Thus SSR markers can be successfully used in marker-assisted selection for powdery mildew resistance breeding in pea.

Ascomycota↗

Ulcerative tracheobronchitis after lung transplantation. A new form of invasive aspergillosis.

Invasive aspergillosis is frequently a fatal disease in the setting of immunosuppression, including organ transplant recipients. The fungus usually affects lung parenchyma and may disseminate from there. We have recently noted tracheobronchitis in six patients with heart-lung and lung transplants, three of whom had deep mucosal ulceration and histologic evidence of invasive aspergillosis. This apparently new form of invasive disease is initially limited to the anastomosis site and large airways. Ulceration, necrosis, cartilage invasion, and formation of a pseudomembrane are the pathologic features. In two patients subsequent disseminated aspergillosis occurred with a fatal outcome. In the two single-lung recipients, disease was limited to the transplanted side emphasizing the importance of abnormal local defense mechanisms in the airways of lung transplant recipients. Routine bronchoscopic examination of the airways is important in early detection of this complication. Oral therapy with the new, antifungal agent itraconazole was successful in five of the six patients, with fatal relapse in one. A classification of the various forms of saprophytic, allergic, and invasive forms of aspergillus tracheobronchitis, to include this new entity, is proposed.

Adult↗

Factors affecting conidial production of Beauveria bassiana from fungus-killed cadavers of Rhodnius prolixus.

The epizootic potential of Beauveria bassiana for control of the triatomine vectors of Chagas' disease was investigated by studying the effects of both biotic and abiotic factors on the recycling of a highly virulent fungal isolate from fungus-killed cadavers of Rhodnius prolixus. The conidial production of B. bassiana from mummified cadavers of R. prolixus required high RH levels of at least 96.5% RH. At 97% RH and 25 degrees C, the amount of conidia per insect ranged from 5.3 x 10(6) (on first-instar larval cadavers) to 1.7 x 10(8) (on adult cadavers) depending on the size of the different stages of development of the host. Under optimal conditions, B. bassiana sporulation from R. prolixus cadavers took place in 4 to 5 days after death. At a high humidity level (97% RH) the intensity of the conidial production from Rhodnius cadavers was little affected by temperature over a range from 15 to 25 degrees C, but it declined at 28-30 degrees C and was null at 35 degrees C. There was only a weak influence of the blood meal of nymphs and its timing on the conidial production from B. bassiana-killed cadavers. The recycling capacity of different B. bassiana isolates, selected for their pathogenic activity to R. prolixus, did not differ. From a vector control standpoint, high humidity appears to be the most crucial climatic constraint. The recycling ability of B. bassiana on fungus-killed R. prolixus might contribute to the regulation of triatomine vectors only after applications during the rainy seasons.

Animals↗

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↗

Fungemia in patients with leukemia.

A nine-year retrospective study on fungemia in patients with leukemia was conducted. A total of 79 episodes of fungemia in 77 patients with leukemia were documented. Candida parapsilosis fungemia was associated more frequently with the presence of a central venous line and to the use of parenteral nutrition than the other fungal species (p = 0.00026 and p = 0.01, respectively). The same fungus was isolated from both blood and surveillance cultures in 95% of Candida albicans and in 89% of Candida tropicalis fungemia (p < 0.01 and p = 0.02, respectively). The neutropenia and fungus colonization that resulted was associated significantly with the presence of invasive disease (p = 0.0024 and p = 0.0028, respectively). Conversely, central venous catheterization and parenteral nutrition appeared to be associated with episodes without deep tissue invasion (p = 0.000037 and p = 0.001, respectively). Invasive mycosis due to the fungus isolated from blood was documented in 51 patients with a mortality rate of 69%, whereas in 20 patients without invasive mycosis, mortality rate was 21% (p = 0.000059). In patients with fungemia, related or unrelated to the presence of a central venous catheter, mortality was 24% and 64%, respectively (p = 0.00042). Mortality was highest with C. tropicalis (p = 0.0017) and lowest with C. parapsilosis (p = 0.057). Severe neutropenia (polymorphonuclears < 100/mmc) appeared associated with a higher mortality rate (p = 0.012), whereas the recovery of neutropenia was related adversely to a fatal outcome (p < 0.01). With antifungal therapy, there was no statistically significant difference whether antifungal therapy was given or not.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A case study of disseminated histoplasmosis linked to common variable immunodeficiency.

Histoplasma capsulatum, a ground fungus, can infect humans, normally in endemic areas; the resulting disease can be asymptomatic or it can have a benign development, but in rare cases it can develop into a serious clinical condition and can even be fatal. Its most characteristic initial location is in the lungs, resembling tuberculosis, often accompanied by mediastinitis and an exuberant fibrotic response. The spread of this infection can be caused by the concomitance of another illness that alters the immunological balance. Sometimes such an association is not clear. Therefore, disseminated histoplasmosis is defined as a clinical condition where the fungus is present in more than one location. Common variable immunodeficiency is characterized by a generalized failure in the synthesis of antibodies, leading the affected individuals to present recurrent infections, especially those caused by encapsulated bacteria, most often involving the respiratory tract. We studied a serious case of disseminated histoplasmosis, accompanied by common variable immunodeficiency, observed at the Infirmary of the department of Medical Practice of the Federal University at Paraná Hospital das Clínicas.

Adult↗

Incidence of Leptosphaerulina crassiasca in symptomless leaves of peanut in southern India.

A Loculoascomycete fungus belonging to the genus Leptosphaerulina was found to survive as symptomless endophyte in the leaflets and rachis of peanut plant (TMV 7). Based on morphological and colony characteristics, it is identified as Leptosphaerulina crassiasca, a fungus that causes the pepper spot and leaf scorch diseases in peanut. Although several common endophytic fungi were recovered from the leaves of peanut, L . crassiasca showed a high relative density of infection. Owing to its endophytic nature, its pathogenicity could not be proved by infection studies. However, its identification as L. crassiasca suggests that this pathogen survives as symptomless endophyte in its host. There are limited studies on fungal endophytes of cultivated crops and hence, the present observation underlines the need to know more about the biology of endophytic fungi of crop plants.

Arachis↗

Crescentic involved glomerulonephritis in infective endocarditis.

The author has analysed the renal alterations in 8 patients, each of whom died of renal failure. Extracapillary crescents had developed in more than 50% of the glomeruli in all of them. Renal symptoms followed those of endocarditis after two weeks. Proteinuria, haematuria and impairment of renal functional parameters featured the clinical course of the disease. From the haemoculture, bacteria (in 6 cases) and fungus (in one case) were isolated. Haemoculture was negative in one case. The obtained serum complement values, intraglomerular immunoglobulin and/or complement depositions, electron-dense deposits along the glomerular basement membrane and within the mesangium all proved the presence of an immunocomplex mechanism. The rapid course leading to renal failure can be explained by the abundant crescent formation.

Adult↗