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Journal ArticleDOI

Further observations on a pathogenic mould formerly described as a protozoon (coccidioides immitis, coccidioides pyogenes)

01 Feb 1905-Journal of Experimental Medicine (The Rockefeller University Press)-Vol. 6, pp 443-485
TL;DR: The disease which formerly has been described as a form of protozoon-infection is due to an infection with a pathogenic fungus that is pathogenic for dogs, rabbits and guinea-pigs probably other animals also, and in them produces lesions very similar to those which the authors encounter in the human being in this disease.
Abstract: From the preceding I derive the following conclusions: 1. The disease which formerly has been described as a form of protozoon-infection is due to an infection with a pathogenic fungus. 2. The infection may primarily be either a cutaneous or a pulmonary one. 3. The lesions produced by this fungus fall under the general head of infectious granulomata and consist partly in nodules resembling altogether those produced by the tubercle bacilli and partly in chronic abscesses. 4. The adult forms of the parasite are more apt to produce nodules, the sporulating forms abscesses. 5. The fungus is pathogenic for dogs, rabbits and guinea-pigs probably other animals also, and in them produces lesions very similar to those which we encounter in the human being in this disease. 6. Supurative periorchitis in guinea-pigs is not pathognomonic for glanders.

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Journal ArticleDOI
TL;DR: This work has constructed robust phylogenies for fungi based on whole genome analysis that provide strong support for the classification of phyla, sub-phyla, classes and orders.
Abstract: To date, most fungal phylogenies have been derived from single gene comparisons, or from concatenated alignments of a small number of genes. The increase in fungal genome sequencing presents an opportunity to reconstruct evolutionary events using entire genomes. As a tool for future comparative, phylogenomic and phylogenetic studies, we used both supertrees and concatenated alignments to infer relationships between 42 species of fungi for which complete genome sequences are available. A dataset of 345,829 genes was extracted from 42 publicly available fungal genomes. Supertree methods were employed to derive phylogenies from 4,805 single gene families. We found that the average consensus supertree method may suffer from long-branch attraction artifacts, while matrix representation with parsimony (MRP) appears to be immune from these. A genome phylogeny was also reconstructed from a concatenated alignment of 153 universally distributed orthologs. Our MRP supertree and concatenated phylogeny are highly congruent. Within the Ascomycota, the sub-phyla Pezizomycotina and Saccharomycotina were resolved. Both phylogenies infer that the Leotiomycetes are the closest sister group to the Sordariomycetes. There is some ambiguity regarding the placement of Stagonospora nodurum, the sole member of the class Dothideomycetes present in the dataset. Within the Saccharomycotina, a monophyletic clade containing organisms that translate CTG as serine instead of leucine is evident. There is also strong support for two groups within the CTG clade, one containing the fully sexual species Candida lusitaniae, Candida guilliermondii and Debaryomyces hansenii, and the second group containing Candida albicans, Candida dubliniensis, Candida tropicalis, Candida parapsilosis and Lodderomyces elongisporus. The second major clade within the Saccharomycotina contains species whose genomes have undergone a whole genome duplication (WGD), and their close relatives. We could not confidently resolve whether Candida glabrata or Saccharomyces castellii lies at the base of the WGD clade. We have constructed robust phylogenies for fungi based on whole genome analysis. Overall, our phylogenies provide strong support for the classification of phyla, sub-phyla, classes and orders. We have resolved the relationship of the classes Leotiomyctes and Sordariomycetes, and have identified two classes within the CTG clade of the Saccharomycotina that may correlate with sexual status.

498 citations

Journal ArticleDOI
TL;DR: Analysis of 18S ribosomal DNA sequences from a diverse group of human pathogenic fungi shows that the specialized, superficial parasite and the systemic, facultative parasites, including C. immitis, are closely related ascomycetes, which clearly demonstrates the power of molecular characters to compensate for missing or confusing reproductive morphology.
Abstract: The morphological, ecological, and clinical diversity among ascomycete fungi that are pathogenic to humans suggest that the potential for pathogenicity may have arisen multiple times within these higher fungi. We have obtained 18S ribosomal DNA sequences from a diverse group of human pathogenic fungi in order to determine their evolutionary origins. The fungi studied include a skin pathogen that is confined to humans (Trichophyton rubrum) and three systemic, facultative parasites that cause histoplasmosis (Histoplasma capsulatum), blastomycosis (Blastomyces dermatitidis) and coccidioidomycosis (Coccidioides immitis) in humans and other higher animals. Also included in our analysis are representatives of non-pathogenic fungi, as well as two opportunistic pathogens, Pneumocystis carinii and Candida albicans, that cause severe disease in immunocompromised individuals, especially those with AIDS. Two of the fungi we sequenced, T. rubrum and C. immitis, are limited to asexual modes of reproduction and therefore lack the sexual structures that are most useful for evolutionary comparison as well as being essential for classification among the higher fungi. Coccidioides immitis is particularly problematic owing to its contradictory and confusing asexual morphologies, which have caused it to be placed in three fungal classes and the protista. Our analysis shows that the specialized, superficial parasite and the systemic, facultative parasites, including C. immitis, are closely related ascomycetes, which clearly demonstrates the power of molecular characters to compensate for missing or confusing reproductive morphology. Analysis also shows that the opportunistic pathogens are more distantly related, with the likely explanation that pathogenicity has arisen more than once within the Ascomycetes.

112 citations

Journal ArticleDOI
TL;DR: Ever since coccidioidal infection has been known to be due to a fungus, it has been recognized that there are two distinct cycles of development of the infecting organism: the form which occurs when the organism has infected animal tissues, and the one which occursWhen the organism grows on culture medium and, presumably, in nature.
Abstract: Ever since coccidioidal infection has been known to be due to a fungus,1it has been recognized that there are two distinct cycles of development of the infecting organism: the form which occurs when the organism has infected animal tissues, and the one which occurs when the organism grows on culture medium and, presumably, in nature. The first of these cycles was that observed when infected human beings came under clinical observation. The parasitic organism was seen as a double-contoured spherule, averaging about 30 microns in diameter, which reproduced by endosporulation, the endospores being released into the tissues by rupture of the wall of the mother spherule. The spherules so closely resembled Coccidia that it was at first believed that they belonged to the protozoan group, and they were called Coccidioides, i. e., like Coccidia; hence the name. The second cycle occurs when the organism grows outside the body,

97 citations

Journal ArticleDOI
TL;DR: A group of evolutionarily related fungal pathogens of humans known as the thermally dimorphic fungi are discussed, which are primary pathogens, with the ability to cause disease in healthy humans who encounter them in endemic areas.
Abstract: Fungi are adept at changing their cell shape and developmental program in response to signals in their surroundings. Here we focus on a group of evolutionarily related fungal pathogens of humans known as the thermally dimorphic fungi. These organisms grow in a hyphal form in the environment but shift their morphology drastically within a mammalian host. Temperature is one of the main host signals that initiates their conversion to the "host" form and is sufficient in the laboratory to trigger establishment of this host-adapted developmental program. Here we discuss the major human pathogens in this group, which are Blastomyces dermatiditis, Coccidioides immitis/posadasii, Histoplasma capsulatum, Paracoccidioides brasiliensis/lutzii, Sporothrix schenckii, and Talaromyces marneffei (formerly known as Penicillium marneffei). The majority of these organisms are primary pathogens, with the ability to cause disease in healthy humans who encounter them in endemic areas.

87 citations