Coccidioides Species: A Review of Basic Research: 2022

Kirkland, Theo N.; Stevens, David A.; Hung, Chiung Yu; Beyhan, Sinem; Taylor, John W.; Shubitz, Lisa F.; Duttke, Sascha H.; Heidari, Arash; Johnson, Royce H.; Deresinski, Stanley C.; Lauer, Antje; Fierer, Joshua

doi:10.3390/jof8080859

Cited by 12 publications

(5 citation statements)

References 172 publications

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“…Molecular studies, including genetic, transcriptional, and proteomic analysis of the fungus, have begun. These were excellently reviewed by Kirkland and colleagues [107], and details will not be covered here. Now that researchers are undertaking these studies however, two important unanswered questions are how the transcriptomic and proteomic findings from cultured organisms compare to parallel studies from infected mouse or patient isolates and how the host response changes during stages of Coccidioides development.…”

Section: Unanswered Questionsmentioning

confidence: 99%

The Known and Unknown “Knowns” of Human Susceptibility to Coccidioidomycosis

Hsu

2024

JoF

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Coccidioidomycosis occurs after inhalation of airborne spores of the endemic, dimorphic fungus, Coccidioides. While the majority of individuals resolve the infection without coming to medical attention, the fungus is a major cause of community-acquired pneumonia in the endemic region, and chronic pulmonary and extrapulmonary disease poses significant personal and economic burdens. This review explores the literature surrounding human susceptibility to coccidioidomycosis, including chronic pulmonary and extrapulmonary dissemination. Over the past century of study, themes have emerged surrounding factors impacting human susceptibility to severe disease or dissemination, including immune suppression, genetic susceptibility, sex, pregnancy, and genetic ancestry. Early studies were observational, frequently with small numbers of cases; several of these early studies are highly cited in review papers, becoming part of the coccidioidomycosis “canon”. Specific genetic variants, sex, and immune suppression by TNF inhibitors have been validated in later cohort studies, confirming the original hypotheses. By contrast, some risk factors, such as ABO blood group, Filipino ancestry, or lack of erythema nodosum among black individuals, are repeated in the literature despite the lack of supporting studies or biologic plausibility. Using examination of historical reports coupled with recent cohort and epidemiology studies, evidence for commonly reported risk factors is discussed.

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Section: Unanswered Questionsmentioning

confidence: 99%

The Known and Unknown “Knowns” of Human Susceptibility to Coccidioidomycosis

Hsu

2024

JoF

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“…The parasitic cycle of Coccidioides is unique amongst the medically important fungi and the ability to form spherules from arthroconidia is required for pathogenicity. Fundamental research on their genetic, morphology, ecology, virulence factors, and pathogenic mechanisms has recently been reviewed [ 4 , 5 ]. Here, we discuss immune responses to coccidioidomycosis in animal models, experiments using human cells in vitro , and clinical observations in humans.…”

Section: Introductionmentioning

confidence: 99%

The Host Response to Coccidioidomycosis

Kirkland,

Hung,

Shubitz

et al. 2024

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Coccidioidomycosis is an important fungal disease that is found in many desert regions of the western hemisphere. The inhaled organisms are highly pathogenic, but only half of infected, immunologically intact people develop symptomatic pneumonia; most symptomatic infections resolve spontaneously, although some resolve very slowly. Furthermore, second infections are very rare and natural immunity after infection is robust. Therefore, the host response to this organism is very effective at resolving the infection in most cases and immunizing to prevent second infections. People who are immunocompromised are much more likely to develop disseminated infection. This is a comprehensive review of the innate and acquired immune responses to Coccidioides spp., the genetics of resistance to severe infection, and the search for an effective vaccine.

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“…Coccidioides spp. (C. immitis and C. posadasii) are dimorphic fungi that grow as mold in the desert soil in the Western hemisphere and form spherules in people and animals [15]. It is a serious human pathogen, frequently causing symptomatic infections and, less commonly, disseminated infections in immunocompetent people as well as the immunocompromised [16,17].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Different Gene Prediction Tools in Coccidioides immitis

Kirkland,

Beyhan,

Stajich

2023

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Gene prediction is required to obtain optimal biologically meaningful information from genomic sequences, but automated gene prediction software is imperfect. In this study, we compare the original annotation of the Coccidioides immitis RS genome (the reference strain of C. immitis) to annotations using the Funannotate and Augustus genome prediction pipelines. A total of 25% of the originally predicted genes (denoted CIMG) were not found in either the Funannotate or Augustus predictions. A comparison of Funannotate and Augustus predictions also found overlapping but not identical sets of genes. The predicted genes found only in the original annotation (referred to as CIMG-unique) were less likely to have a meaningful functional annotation and a lower number of orthologs and homologs in other fungi than all CIMG genes predicted by the original annotation. The CIMG-unique genes were also more likely to be lineage-specific and poorly expressed. In addition, the CIMG-unique genes were found in clusters and tended to be more frequently associated with transposable elements than all CIMG-predicted genes. The CIMG-unique genes were more likely to have experimentally determined transcription start sites that were further away from the originally predicted transcription start sites, and experimentally determined initial transcription was less likely to result in stable CIMG-unique transcripts. A sample of CIMG-unique genes that were relatively well expressed and differentially expressed in mycelia and spherules was inspected in a genome browser, and the structure of only about half of them was found to be supported by RNA-seq data. These data suggest that some of the CIMG-unique genes are not authentic gene predictions. Genes that were predicted only by the Funannotate pipeline were also less likely to have a meaningful functional annotation, be shorter, and express less well than all the genes predicted by Funannotate. C. immitis genes predicted by more than one annotation are more likely to have predicted functions, many orthologs and homologs, and be well expressed. Lineage-specific genes are relatively uncommon in this group. These data emphasize the importance and limitations of gene prediction software and suggest that improvements to the annotation of the C. immitis genome should be considered.

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Coccidioides Species: A Review of Basic Research: 2022

Cited by 12 publications

References 172 publications

The Known and Unknown “Knowns” of Human Susceptibility to Coccidioidomycosis

The Known and Unknown “Knowns” of Human Susceptibility to Coccidioidomycosis

The Host Response to Coccidioidomycosis

Evaluation of Different Gene Prediction Tools in Coccidioides immitis

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