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Frontiers in Cellular and Infection... 2020and are related thermally dimorphic fungal pathogens that cause deadly mycoses (i.e., histoplasmosis and paracoccidioidomycosis, respectively) primarily in North,... (Review)
Review
and are related thermally dimorphic fungal pathogens that cause deadly mycoses (i.e., histoplasmosis and paracoccidioidomycosis, respectively) primarily in North, Central, and South America. Mammalian infection results from inhalation of conidia and their subsequent conversion into pathogenic yeasts. Macrophages in the lung are the first line of defense, but are generally unable to clear these fungi. Instead, and yeasts survive and proliferate within the phagosomal compartment of host macrophages. Growth within macrophages requires strategies for acquisition of sufficient nutrients (e.g., carbon, nitrogen, and essential trace elements and co-factors) from the nutrient-depleted phagosomal environment. We review the transcriptomic and recent functional genetic studies that are defining how these intracellular fungal pathogens tune their metabolism to the resources available in the macrophage phagosome. In addition, recent studies have shown that the nutritional state of the macrophage phagosome is not static, but changes upon activation of adaptive immune responses. Understanding the metabolic requirements of these dimorphic pathogens as they thrive within host cells can provide novel targets for therapeutic intervention.
Topics: Animals; Histoplasma; Histoplasmosis; Macrophages; Paracoccidioides; Paracoccidioidomycosis
PubMed: 33178634
DOI: 10.3389/fcimb.2020.592259 -
Cold Spring Harbor Perspectives in... Nov 2014The innate immune system is a critical line of defense against pathogenic fungi. Macrophages act at an early stage of infection, detecting and phagocytizing infectious... (Review)
Review
The innate immune system is a critical line of defense against pathogenic fungi. Macrophages act at an early stage of infection, detecting and phagocytizing infectious propagules. To avoid killing at this stage, fungal pathogens use diverse strategies ranging from evasion of uptake to intracellular parasitism. This article will discuss five of the most important human fungal pathogens (Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans, Coccidiodes immitis, and Histoplasma capsulatum) and consider the strategies and virulence factors adopted by each to survive and replicate within macrophages.
Topics: Aspergillus fumigatus; Candida albicans; Cryptococcus neoformans; Histoplasma; Humans; Macrophages; Virulence Factors
PubMed: 25384769
DOI: 10.1101/cshperspect.a019661 -
BioMed Research International 2015Healthcare-associated infections (HAI) are described in diverse settings. The main etiologic agents of HAI are bacteria (85%) and fungi (13%). Some factors increase the... (Review)
Review
Healthcare-associated infections (HAI) are described in diverse settings. The main etiologic agents of HAI are bacteria (85%) and fungi (13%). Some factors increase the risk for HAI, particularly the use of medical devices; patients with severe cuts, wounds, and burns; stays in the intensive care unit, surgery, and hospital reconstruction works. Several fungal HAI are caused by Candida spp., usually from an endogenous source; however, cross-transmission via the hands of healthcare workers or contaminated devices can occur. Although other medically important fungi, such as Blastomyces dermatitidis, Paracoccidioides brasiliensis, and Histoplasma capsulatum, have never been considered nosocomial pathogens, there are some factors that point out the pros and cons for this possibility. Among these fungi, H. capsulatum infection has been linked to different medical devices and surgery implants. The filamentous form of H. capsulatum may be present in hospital settings, as this fungus adapts to different types of climates and has great dispersion ability. Although conventional pathogen identification techniques have never identified H. capsulatum in the hospital environment, molecular biology procedures could be useful in this setting. More research on H. capsulatum as a HAI etiologic agent is needed, since it causes a severe and often fatal disease in immunocompromised patients.
Topics: Blastomyces; Candida; Cross Infection; Equipment and Supplies; Histoplasma; Humans; Paracoccidioides
PubMed: 26106622
DOI: 10.1155/2015/982429 -
Future Microbiology 2015Histoplasma capsulatum, an environmental fungus, is the most common endemic pulmonary mycosis in the USA. Disease is most frequently observed in immunocompromised... (Review)
Review
Histoplasma capsulatum, an environmental fungus, is the most common endemic pulmonary mycosis in the USA. Disease is most frequently observed in immunocompromised patients living in endemic areas. We present the mechanisms of fungal recognition, innate immune response and adaptive immune response that lead to protection or exacerbation of disease. Current understanding of these mechanisms is the result of a continuing dialogue between clinical observations and murine studies. Mice are a powerful model to study the immune response to H. capsulatum alone or in the presence of immunomodulatory drugs. Vigilance for histoplasmosis should be exercised with novel immunosuppressive agents that target the important immune pathways identified here.
Topics: Adaptive Immunity; Animals; Disease Models, Animal; Endemic Diseases; Histoplasma; Histoplasmosis; Humans; Immunity, Innate; Immunocompromised Host; Lung Diseases, Fungal; Mice; Opportunistic Infections; United States
PubMed: 26059620
DOI: 10.2217/fmb.15.25 -
PLoS Pathogens Sep 2018
Review
Topics: Animals; Birds; Chiroptera; Disease Outbreaks; Disease Reservoirs; Histoplasma; Histoplasmosis; Humans; Soil Microbiology; Spores, Fungal
PubMed: 30212569
DOI: 10.1371/journal.ppat.1007213 -
Current Opinion in Microbiology Dec 2017Mammalian body temperature triggers differentiation of the fungal pathogen Histoplasma capsulatum into yeast cells. The Drk1 regulatory kinase and an interdependent... (Review)
Review
Mammalian body temperature triggers differentiation of the fungal pathogen Histoplasma capsulatum into yeast cells. The Drk1 regulatory kinase and an interdependent network of Ryp transcription factors establish the yeast state. Beyond morphology, the differentiation-dependent expression program equips yeasts for invasion and survival within phagosomes. Yeast cells produce α-glucan and the Eng1 endoglucanase which hide yeasts from immune detection. Secretion of yeast phase-specific Sod3 and CatB detoxify phagocyte-derived reactive oxygen molecules. Histoplasma cells adapt to iron and zinc limitation in activated macrophages by production of siderophores and the Zrt2 transporter, respectively. Yeasts also respond to inflammation-associated hypoxia. Histoplasma pathogenicity thus relies on factors controlled by yeast differentiation as well as environment-dependent responses.
Topics: Animals; Fungal Proteins; Histoplasma; Histoplasmosis; Humans; Phagocytes
PubMed: 29096192
DOI: 10.1016/j.mib.2017.10.003 -
The American Journal of Tropical... Jun 2014
Topics: Africa South of the Sahara; Asia; Endemic Diseases; HIV Infections; Histoplasma; Histoplasmosis; Humans; Madagascar
PubMed: 24778192
DOI: 10.4269/ajtmh.14-0175 -
MBio Feb 2022Histoplasma capsulatum, a dimorphic fungal pathogen, is the most common cause of fungal respiratory infections in immunocompetent hosts. is endemic in the Ohio and...
Histoplasma capsulatum, a dimorphic fungal pathogen, is the most common cause of fungal respiratory infections in immunocompetent hosts. is endemic in the Ohio and Mississippi River Valleys in the United States and is also distributed worldwide. Previous studies have revealed at least eight clades, each specific to a geographic location: North American classes 1 and 2 (NAm 1 and NAm 2), Latin American groups A and B (LAm A and LAm B), Eurasian, Netherlands, Australian and African, and an additional distinct lineage (H81) comprised of Panamanian isolates. Previously assembled genomes are highly fragmented, with the highly repetitive G217B (NAm 2) strain, which has been used for most whole-genome-scale transcriptome studies, assembled into over 250 contigs. In this study, we set out to fully assemble the repeat regions and characterize the large-scale genome architecture of species. We resequenced five strains (WU24 [NAm 1], G217B [NAm 2], H88 [African], G186AR [Panama], and G184AR [Panama]) using Oxford Nanopore Technologies long-read sequencing technology. Here, we report chromosomal-level assemblies for all five strains, which exhibit extensive synteny among the geographically distant isolates. The new assemblies revealed that , a major regulator of morphology and virulence, is duplicated in G186AR. In addition, we mapped previously generated transcriptome data sets onto the newly assembled chromosomes. Our analyses revealed that the expression of transposons and transposon-embedded genes are upregulated in yeast phase compared to mycelial phase in the G217B and H88 strains. This study provides an important resource for fungal researchers and further highlights the importance of chromosomal-level assemblies in analyzing high-throughput data sets. species are dimorphic fungi causing significant morbidity and mortality worldwide. These fungi grow as mold in the soil and as budding yeast within the human host. can be isolated from soil in diverse regions, including North America, South America, Africa, and Europe. Phylogenetically distinct species of have been isolated and sequenced. However, for the commonly used strains, genome assemblies have been fragmented, leading to underutilization of genome-scale data. This study provides chromosome-level assemblies of the commonly used strains using long-read sequencing technology. Comparative analysis of these genomes shows largely conserved gene order within the chromosomes. Mapping existing transcriptome data on these new assemblies reveals clustering of transcriptionally coregulated genes. The results of this study highlight the importance of obtaining chromosome-level assemblies in understanding the biology of human fungal pathogens.
Topics: Humans; Synteny; Australia; Histoplasma; Mycoses; Saccharomyces cerevisiae; Chromosomes; Genome, Fungal
PubMed: 35089059
DOI: 10.1128/mbio.02574-21 -
Virulence Dec 2022Histoplasmosis is a systemic mycosis caused by the thermally dimorphic fungus . Although healthy individuals can develop histoplasmosis, the disease is particularly... (Review)
Review
Histoplasmosis is a systemic mycosis caused by the thermally dimorphic fungus . Although healthy individuals can develop histoplasmosis, the disease is particularly life-threatening in immunocompromised patients, with a wide range of clinical manifestations depending on the inoculum and virulence of the infecting strain. In this review, we discuss the established virulence factors and pathogenesis traits that make highly adapted to a wide variety of hosts, including mammals. Understanding and integrating these mechanisms is a key step toward devising new preventative and therapeutic interventions.
Topics: Animals; Humans; Histoplasma; Histoplasmosis; Virulence; Adaptation, Physiological; Virulence Factors; Mammals
PubMed: 36266777
DOI: 10.1080/21505594.2022.2137987 -
Virulence Dec 2019is a member of a group of fungal pathogens called thermally dimorphic fungi, all of which respond to mammalian body temperature by converting from an environmental mold... (Review)
Review
is a member of a group of fungal pathogens called thermally dimorphic fungi, all of which respond to mammalian body temperature by converting from an environmental mold form into a parasitic host form that causes disease. is a primary fungal pathogen, meaning it is able to cause disease in healthy individuals. We are beginning to understand how host temperature is utilized as a key signal to facilitate growth in the parasitic yeast form and promote production of virulence factors. In recent years, multiple regulators of morphology and virulence have been identified in . Mutations in these regulators render the pathogen unable to convert to the parasitic yeast form. Additionally, several virulence factors have been characterized for their importance in survival and pathogenesis. These virulence factors and regulators can serve as molecular handles for the development of effective drugs and therapeutics to counter infection.
Topics: Animals; Body Temperature; Gene Expression Regulation, Fungal; Histoplasma; Histoplasmosis; Host-Pathogen Interactions; Humans; Mice; Mutation; Virulence; Virulence Factors
PubMed: 31560240
DOI: 10.1080/21505594.2019.1663596