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Memorias Do Instituto Oswaldo Cruz May 2009Histoplasma capsulatum is an intracellular fungal pathogen that causes respiratory and systemic disease by proliferating within phagocytic cells. The binding of H.... (Review)
Review
Histoplasma capsulatum is an intracellular fungal pathogen that causes respiratory and systemic disease by proliferating within phagocytic cells. The binding of H. capsulatum to phagocytes may be mediated by the pathogen's cell wall carbohydrates, glucans, which consist of glucose homo and hetero-polymers and whose glycosydic linkage types differ between the yeast and mycelial phases. The alpha-1,3-glucan is considered relevant for H. capsulatum virulence, whereas the beta-1,3-glucan is antigenic and participates in the modulation of the host immune response. H. capsulatum cell wall components with lectin-like activity seem to interact with the host cell surface, while host membrane lectin-like receptors can recognize a particular fungal carbohydrate ligand. This review emphasizes the relevance of the main H. capsulatum and host carbohydrate-driven interactions that allow for binding and internalization of the fungal cell into phagocytes and its subsequent avoidance of intracellular elimination.
Topics: Animals; Carbohydrates; Cell Wall; Histoplasma; Histoplasmosis; Host-Parasite Interactions; Humans; Immunologic Factors
PubMed: 19547878
DOI: 10.1590/s0074-02762009000300016 -
Emerging Infectious Diseases Nov 2018We describe a case series of histoplasmosis caused by Histoplasma capsulatum var. duboisii during July 2011-January 2014 in Kimpese, Democratic Republic of the Congo....
We describe a case series of histoplasmosis caused by Histoplasma capsulatum var. duboisii during July 2011-January 2014 in Kimpese, Democratic Republic of the Congo. Cases were confirmed by histopathology, immunohistochemistry, and reverse transcription PCR. All patients were HIV negative. Putative sources for the pathogen were cellar bats and guano fertilizer exploitation.
Topics: Adolescent; Adult; Child; Child, Preschool; Democratic Republic of the Congo; Female; Histoplasma; Histoplasmosis; Humans; Immunohistochemistry; Male; Middle Aged; Young Adult
PubMed: 30334708
DOI: 10.3201/eid2411.180236 -
Biodiverse Species Elicit Distinct Patterns of Pulmonary Inflammation following Sublethal Infection.MSphere Aug 2020is an endemic dimorphic fungus that can cause disease in healthy and immunocompromised individuals after the transition of inhaled spores into the facultative...
is an endemic dimorphic fungus that can cause disease in healthy and immunocompromised individuals after the transition of inhaled spores into the facultative intracellular yeast form. There is substantial diversity among species, but it is not clear how this heterogeneity impacts the progression of pathology and cellular immune responses during acute respiratory infection, which represents the vast majority of histoplasmosis disease burden. After inoculating mice intranasally with a sublethal inoculum, we characterized the immune response to (strain G186A) and (strain G217B) using comprehensive flow cytometric and single-cell analyses. Within 8 days after inoculation, induced a significantly higher infiltration of neutrophils and inflammatory monocytes into the lung compared to Microscopic analysis of infected lung tissue revealed that although the total number of fungi was similar within inflamed lung lesions, we observed different species-dependent intracellular yeast distribution patterns. Inoculation with -expressing strains indicated that , but not , was associated primarily with alveolar macrophages early after infection. Interestingly, we observed a significant reduction in the total number of alveolar macrophages 12 to 16 days after but not infection, despite similar intracellular growth dynamics within AMJ2-C11 alveolar macrophages Together, our data suggest that , but not , preferentially interacts with alveolar macrophages early after infection, which may lead to a different course of inflammation and resolution despite similar rates of fungal clearance. Acute pulmonary histoplasmosis in healthy individuals comprises most of the disease burden caused by the fungal pathogen Fungal pneumonia is frequently delayed in diagnosis and treatment due to a prolonged period of quiescence early during infection. In this study, we used a murine respiratory model of histoplasmosis to investigate how different species modulate lung inflammation throughout the complete course of infection. We propose that a relatively low, sublethal inoculum is ideal to model acute pulmonary histoplasmosis in humans, primarily due to the quiescent stage of fungal growth that occurs in the lungs of mice prior to the initiation of inflammation. Our results reveal the unique course of lung immunity associated with divergent species of and imply that the progression of clinical disease is considerably more heterogeneous than previously recognized.
Topics: Animals; Disease Models, Animal; Flow Cytometry; Genetic Variation; Histoplasma; Histoplasmosis; Lung; Macrophages, Alveolar; Male; Mice; Mice, Inbred C57BL; Pneumonia
PubMed: 32848006
DOI: 10.1128/mSphere.00742-20 -
MBio Jan 2018The ability to grow at mammalian body temperatures is critical for pathogen infection of humans. For the thermally dimorphic fungal pathogen , elevated temperature is...
The ability to grow at mammalian body temperatures is critical for pathogen infection of humans. For the thermally dimorphic fungal pathogen , elevated temperature is required for differentiation of mycelia or conidia into yeast cells, a step critical for invasion and replication within phagocytic immune cells. Posttranslational glycosylation of extracellular proteins characterizes factors produced by the pathogenic yeast cells but not those of avirulent mycelia, correlating glycosylation with infection. yeast cells lacking the Pmt1 and Pmt2 protein mannosyltransferases, which catalyze O-linked mannosylation of proteins, are severely attenuated during infection of mammalian hosts. Cells lacking Pmt2 have altered surface characteristics that increase recognition of yeast cells by the macrophage mannose receptor and reduce recognition by the β-glucan receptor Dectin-1. Despite these changes, yeast cells lacking these factors still associate with and survive within phagocytes. Depletion of macrophages or neutrophils does not recover the virulence of the mutant yeast cells. We show that yeast cells lacking Pmt functions are more sensitive to thermal stress and consequently are unable to productively infect mice, even in the absence of fever. Treatment of mice with cyclophosphamide reduces the normal core body temperature of mice, and this decrease is sufficient to restore the infectivity of O-mannosylation-deficient yeast cells. These findings demonstrate that O-mannosylation of proteins increases the thermotolerance of yeast cells, which facilitates infection of mammalian hosts. For dimorphic fungal pathogens, mammalian body temperature can have contrasting roles. Mammalian body temperature induces differentiation of the fungal pathogen into a pathogenic state characterized by infection of host phagocytes. On the other hand, elevated temperatures represent a significant barrier to infection by many microbes. By functionally characterizing cells lacking O-linked mannosylation enzymes, we show that protein mannosylation confers thermotolerance on , enabling infection of mammalian hosts.
Topics: Animals; Disease Models, Animal; Fungal Proteins; Histoplasma; Histoplasmosis; Mannosyltransferases; Mice, Inbred C57BL; Microbial Viability; Protein Processing, Post-Translational; Virulence
PubMed: 29295913
DOI: 10.1128/mBio.02121-17 -
Mycopathologia Feb 1982Recently we described a strain of Histoplasma capsulatum, designated H-35, which is able to grow as yeast on a minimal medium consisting of inorganic salts, glucose and...
Recently we described a strain of Histoplasma capsulatum, designated H-35, which is able to grow as yeast on a minimal medium consisting of inorganic salts, glucose and a trace of biotin. Using this strain as a prototrophic wild type we sought auxotrophic mutants. Mutagenized yeast-cells were starved for inorganic sulfate in sulfur-free minimal medium. Sulfate was then added, and growing prototrophic cells were killed by addition of amphotericin B. After 24 hours non-growing auxotrophs were 'rescued' by removal of amphotericin and addition of yeast extract. This 'mutant enrichment' cycle was repeated two additional times, after which the cells were plated on blood agar and 800 yeast-colonies were picked. Seventeen of these yeast-strains required cysteine for growth, as compared with strain H-35, which grew as yeast on minimal medium.
Topics: Amphotericin B; Culture Media; Cysteine; Histoplasma; Mutation
PubMed: 7070482
DOI: 10.1007/BF00437386 -
Mycopathologia Apr 2009Skin lesions, uncommon in US cases (<10%), occur in 38-85% of cases reported from Latin America. Although these differences may reflect reporting bias, delayed...
Two specific strains of Histoplasma capsulatum causing mucocutaneous manifestations of histoplasmosis: preliminary analysis of a frequent manifestation of histoplasmosis in southern Brazil.
OBJECTIVES
Skin lesions, uncommon in US cases (<10%), occur in 38-85% of cases reported from Latin America. Although these differences may reflect reporting bias, delayed diagnosis, or differences in host immune response among different ethnic groups, they also could result from genetic differences changing the pathobiology of the organism. It is possible that genetic differences among strains of H. capsulatum may influence the pathogenesis and clinical manifestations of histoplasmosis.
METHODS
We examined the clinical features of patients with mucocutaneous manifestations of histoplasmosis and performed genetic analysis based on nucleotide sequence variations in the internal transcribed spacer regions of rRNA genes of H. capsulatum isolates of patients. Two pairs of PCR primers were designed to develop and amplify the ITS regions of H. capsulatum, 5'-TACCCGGCCACCCTTGTCTA-3' and 5'-AGCGGGTGGCAAAGCCC-3'. These primers were based on the ITS sequence of Ajellomyces capsulatus, the ascomycetous teleomorph form of H. capsulatum, deposited in the GenBank (accession number U18363). Eight patients attending a tertiary-care hospital in southern Brazil were enrolled into the study. All case patients had skin cultures growing H. capsulatum at the mycology laboratory.
RESULTS
Six of eight (75%) patients were HIV-positive and presented involvement of multiples organs by H. capsulatum. Two HIV-negative patients did not present evidence of involvement of other organs besides mucosa and skin. ITS sequencing of a DNA H. capsulatum fragment of 485-bp from isolates of 8 patients revealed two distinct strains. The 2 distinct fragments (Hc1, Hc2) differed from each other at 7 positions in the ITS regions. They were identical to strains of H. capsulatum isolated in patients from Colombia and Argentina, but different from strains isolated in US. Hc1 and Hc2 were isolated in 5 patients and 3 patients, respectively, with mucocutaneous manifestations of histoplasmosis. Both Hc1 and Hc2 strains were isolated in HIV-infected and non-HIV-infected patients.
CONCLUSIONS
Mucocutaneous manifestations of histoplasmosis, which are frequently seen in Brazilian patients were caused by 2 specific strains in our institution. Those strains have been isolated in patients with these particular clinical features of histoplasmosis in Latin America. Our study suggests that unique pathogenic characteristics among the Latin American species of H. capsulatum might explain its increased dermatotropism.
Topics: AIDS-Related Opportunistic Infections; Adult; Base Sequence; Brazil; DNA, Fungal; DNA, Ribosomal Spacer; Dermatomycoses; Female; Genetic Variation; Histoplasma; Histoplasmosis; Humans; Male; Middle Aged; Molecular Sequence Data; Mycological Typing Techniques; Polymerase Chain Reaction; RNA, Ribosomal, 5.8S; Species Specificity
PubMed: 19112605
DOI: 10.1007/s11046-008-9171-7 -
Mycopathologia Oct 2020Histoplasmosis is a worldwide systemic endemic mycosis caused by several cryptic species included within the Histoplasma capsulatum complex. Domestic and wild mammals...
Histoplasmosis is a worldwide systemic endemic mycosis caused by several cryptic species included within the Histoplasma capsulatum complex. Domestic and wild mammals are susceptible to infection by this fungus and could be used as indicators of its presence in the environment. The aim of the study was to identify the natural reservoirs of H. capsulatum in the Argentinean Humid Pampas eco-region analyzing a wildlife frozen-tissue collection and trace its distribution patterns over time and space. Tissue samples from 34 small wild mammals caught in the Humid Pampas were analyzed using two molecular markers: 100 kDa protein coding gene (Hcp100) and ITS1 rDNA. Results showed that 32.4% of them were infected with H. capsulatum and its DNA was detected in 5/17 Calomys laucha; 3/6 Calomys musculinus; 1/5 Akodon azarae, 1/3 Monodelphis dimidiata; and 1/2 Didelphis albiventris. In the single specimen studied of Cavia aperea, no H. capsulatum DNA was detected. This is the first H. capsulatum infection report in C. laucha and C. musculinus rodents and M. dimidiate opossum which proves that tissue collections are an important source of material for epidemiological studies of endemic disease over time.
Topics: Animals; Animals, Wild; Argentina; DNA, Fungal; Disease Reservoirs; Endemic Diseases; Epidemiologic Studies; Histoplasma; Histoplasmosis; Humans; Tissue Banks; Zoonoses
PubMed: 31993951
DOI: 10.1007/s11046-020-00430-3 -
MSphere Jun 2024Histoplasmosis is an endemic mycosis that often presents as a respiratory infection in immunocompromised patients. Hundreds of thousands of new infections are reported...
Histoplasmosis is an endemic mycosis that often presents as a respiratory infection in immunocompromised patients. Hundreds of thousands of new infections are reported annually around the world. The etiological agent of the disease, is a dimorphic fungus commonly found in the soil where it grows as mycelia. Humans can become infected by through inhalation of its spores (conidia) or mycelial particles. The fungi transition into the yeast phase in the lungs at 37°C. Once in the lungs, yeast cells reside and proliferate inside alveolar macrophages. Genomic work has revealed that is composed of at least five cryptic phylogenetic species that differ genetically. Three of those lineages have received new names. Here, we evaluated multiple phenotypic characteristics (colony morphology, secreted proteolytic activity, yeast size, and growth rate) of strains from five of the phylogenetic species of to identify phenotypic traits that differentiate between these species: , , , , and an African lineage. We report diagnostic traits for three species. The other two species can be identified by a combination of traits. Our results suggest that (i) there are significant phenotypic differences among the cryptic species of and (ii) those differences can be used to positively distinguish those species in a clinical setting and for further study of the evolution of this fungal pathogen.IMPORTANCEIdentifying species boundaries is a critical component of evolutionary biology. Genome sequencing and the use of molecular markers have advanced our understanding of the evolutionary history of fungal pathogens, including , and have allowed for the identification of new species. This is especially important in organisms where morphological characteristics have not been detected. In this study, we revised the taxonomic status of the four named species of the genus (), , , and and propose the use of species-specific phenotypic traits to aid their identification when genome sequencing is not available. These results have implications not only for evolutionary study of but also for clinicians, as the species could determine the outcome of disease and treatment needed.
Topics: Histoplasma; Phenotype; Phylogeny; Histoplasmosis; Humans; Genome, Fungal
PubMed: 38771035
DOI: 10.1128/msphere.00009-24 -
Emerging Microbes & Infections Dec 2024Histoplasmosis is an endemic mycosis in North America frequently reported along the Ohio and Mississippi River Valleys, although autochthonous cases occur in non-endemic...
Histoplasmosis is an endemic mycosis in North America frequently reported along the Ohio and Mississippi River Valleys, although autochthonous cases occur in non-endemic areas. In the United States, the disease is provoked by two genetically distinct clades of , (Nam1) and (Nam2). To bridge the molecular epidemiological gap, we genotyped 93 isolates (62 novel genomes) including clinical, environmental, and veterinarian samples from a broader geographical range by whole-genome sequencing, followed by evolutionary and species niche modelling analyses. We show that histoplasmosis is caused by two major lineages, and ; with sporadic cases caused by in California and Texas. While is prevalent in eastern states, was found to be prevalent in the central and western portions of the United States, but also geographically overlapping in some areas suggesting that these species might co-occur. Species Niche Modelling revealed that thrives in places with warmer and drier conditions, while is endemic to areas with cooler temperatures and more precipitation. In addition, we predicted multiple areas of secondary contact zones where the two species co-occur, potentially facilitating gene exchange and hybridization. This study provides the most comprehensive understanding of the genomic epidemiology of histoplasmosis in the USA and lays a blueprint for the study of invasive fungal diseases.
Topics: Histoplasmosis; Histoplasma; Genotype; Genomics; Texas
PubMed: 38465644
DOI: 10.1080/22221751.2024.2315960 -
Medical Mycology Nov 2018Bats are considered to play a significant role in the epidemiology of histoplasmosis, worldwide. We investigated the occurrence of H. capsulatum in lung samples from 89...
Bats are considered to play a significant role in the epidemiology of histoplasmosis, worldwide. We investigated the occurrence of H. capsulatum in lung samples from 89 bats, from urban areas in Southeastern Brazil, using nested PCR based on ribosomal DNA. Fungal DNA was detected in 31/89 samples (34.8%), of which 13/31 were Molossids (41.9%), 4/31 Eumops spp. (12.9%), 2/31 Artibeus lituratus (6.5%), and 12/31 others (38.7%). This is the first report of natural infection by H. capsulatum in A. lituratus in Southeastern Brazil, which reinforces the importance of these synanthropic animals in the epidemiology of histoplasmosis in urban areas.
Topics: Animals; Brazil; Chiroptera; Cities; Cross-Sectional Studies; DNA, Fungal; DNA, Ribosomal; Histoplasma; Histoplasmosis; Lung; Polymerase Chain Reaction
PubMed: 29294049
DOI: 10.1093/mmy/myx138