The Host Response to Coccidioidomycosis.

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.

Evaluation of Different Gene Prediction Tools in .

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 RS genome (the reference strain of ) 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.

Coccidioides Species: A Review of Basic Research: 2022.

and are closely related fungal species that cause coccidioidomycosis. These dimorphic organisms cause disease in immunocompetent as well as immunocompromised individuals and as much as 40% of the population is infected in the endemic area. Although most infections resolve spontaneously, the infection can be prolonged and, in some instances, fatal.

Decoding Transcription Regulatory Mechanisms Associated with Phase Transition Using Total RNA.

New or emerging infectious diseases are commonly caused by pathogens that cannot be readily manipulated or studied under common laboratory conditions. These limitations hinder standard experimental approaches and our abilities to define the fundamental molecular mechanisms underlying pathogenesis. The advance of capped small RNA sequencing (csRNA-seq) now enables genome-wide mapping of actively initiated transcripts from genes and other regulatory transcribed start regions (TSRs) such as enhancers at a precise moment from total RNA.

Transcriptional Analysis of Mycelia and Spherules by RNA Sequencing.

and   are dimorphic fungi that transform from mycelia with internal arthroconidia in the soil to a tissue form known as a spherule in mammals. This process can be recapitulated in vitro by increasing the temperature, CO and changing other culture conditions. In this study, we have analyzed changes in gene expression in mycelia and young and mature spherules.

Innate Immune Receptors and Defense Against Primary Pathogenic Fungi.

The innate immune system is critical for natural resistance to all pathogenic microorganisms, including fungi. The innate response plays a vital role in resistance to infections before the antigen-specific immune response and also influences antigen-specific adaptive immunity. There are many different receptors for the innate immune response to fungi, and some receptors have been found to play a significant role in the response to human infections with opportunistic fungi.

Coccidioides immitis and posadasii; A review of their biology, genomics, pathogenesis, and host immunity.

Coccidioides immitis and C. posadasii are two highly pathogenic dimorphic fungal species that are endemic in the arid areas of the new world, including the region from west Texas to southern and central California in the USA that cause coccidioidomycosis (also known as Valley Fever). In highly endemic regions such as southern Arizona, up to 50% of long term residents have been infected.

Special Issue: Genomic Data in Pathogenic Fungi.

This special issue, "Genomic Data in Pathogenic Fungi," focuses on the genomics of human and plant pathogens. Efforts like this are important because so little information about these organisms is available.[.

The Quest for a Vaccine Against Coccidioidomycosis: A Neglected Disease of the Americas.

Coccidioidomycosis (Valley Fever) is a disease caused by inhalation of spp. This neglected disease has substantial public health impact despite its geographic restriction to desert areas of the southwestern U.S.

Analysis of Transposable Elements in Coccidioides Species.

and are primary pathogenic fungi that cause disease in immunologically-normal animals and people. The organism is found exclusively in arid regions of the Southwestern United States, Mexico, and South America, but not in other parts of the world. This study is a detailed analysis of the transposable elements (TE) in spp.

A few shared up-regulated genes may influence conidia to yeast transformation in dimorphic fungal pathogens.

The small number of fungi that commonly cause disease in normal people share the capacity to grow as mycelia in the soil at 25°C and as yeast (or spherules) in mammals at 37°C. This remarkable conversion has long been a topic of interest in medical mycology. The conidia to yeast conversion has been studied by transcription profiling in several fungal species, including Histoplasma capsulatum, Paracoccidioides brasiliensis, Coccidioides spp.

Gene expression in human fungal pathogen Coccidioides immitis changes as arthroconidia differentiate into spherules and mature.

Background: Coccidioides immitis is a dimorphic fungus that causes disease in mammals, including human beings. It grows as a mycelium containing arthroconidia in the soil and in the host arthroconidia differentiates into a unique structure called a spherule. We used a custom open reading frame oligonucleotide microarray to compare the transcriptome of C.

Factors regulated by interferon gamma and hypoxia-inducible factor 1A contribute to responses that protect mice from Coccidioides immitis infection.

Background: Coccidioidomycosis results from airborne infections caused by either Coccidioides immitis or C. posadasii. Both are pathogenic fungi that live in desert soil in the New World and can infect normal hosts, but most infections are self-limited.

The role of reactive oxygen intermediates in experimental coccidioidomycois in mice.

Background: Coccidioidomycosis is usually a self-limited infection in immunocompentent people. In immunocompentent human beings second infections due to Coccidioides are very rare, indicating that recovery from infection results in protective immunity. In experimental animals, immunization with several different proteins or attenuated mutants protects against a virulent challenge.

Population genomic sequencing of Coccidioides fungi reveals recent hybridization and transposon control.

We have sequenced the genomes of 18 isolates of the closely related human pathogenic fungi Coccidioides immitis and Coccidioides posadasii to more clearly elucidate population genomic structure, bringing the total number of sequenced genomes for each species to 10. Our data confirm earlier microsatellite-based findings that these species are genetically differentiated, but our population genomics approach reveals that hybridization and genetic introgression have recently occurred between the two species. The directionality of introgression is primarily from C.

Comparative genomic analyses of the human fungal pathogens Coccidioides and their relatives.

While most Ascomycetes tend to associate principally with plants, the dimorphic fungi Coccidioides immitis and Coccidioides posadasii are primary pathogens of immunocompetent mammals, including humans. Infection results from environmental exposure to Coccidiodies, which is believed to grow as a soil saprophyte in arid deserts. To investigate hypotheses about the life history and evolution of Coccidioides, the genomes of several Onygenales, including C.

Characterization of monoclonal antibodies to human soluble MD-2 protein.

Toll-like receptors (TLRs) are mammalian innate immune recognition receptors that are activated by pathogen associated molecular patterns (PAMPs). TLR4 is the signaling molecule of the lipopolysaccharide (LPS) receptor complex. TLR4 associates with its adapter molecule, MD-2, which is absolutely required for LPS-induced activation of TLR4.

Improved protection of mice against lethal respiratory infection with Coccidioides posadasii using two recombinant antigens expressed as a single protein.

Two recombinant antigens which individually protect mice from lethal intranasal infection were studied in combination, either as a mixture of two separately expressed proteins or as a single chimeric expression product. Mice vaccinated with either combination survived longer than mice given single antigens. Immunized mice also exhibited specific IgG immunoglobulins and yielded splenocytes which produced interferon-gamma in response to either antigen.

Mutational analysis of membrane and soluble forms of human MD-2.

Toll-like receptor 4 and MD-2 form a receptor for lipopolysaccharide (LPS), a major constituent of Gram-negative bacteria. MD-2 is a 20-25-kDa extracellular glycoprotein that binds to Tolllike receptor 4 (TLR4) and LPS and is a critical part of the LPS receptor. Here we have shown that the level of MD-2 expression regulates TLR4 activation by LPS.

Toll-like receptor 4 protects against lethal Leptospira interrogans serovar icterohaemorrhagiae infection and contributes to in vivo control of leptospiral burden.

The roles of innate immune responses in protection from or pathogenesis of severe leptospirosis remain unclear. We examined the role of Toll-like receptors (TLRs) in mouse infection and macrophage responses to Leptospira. C3H/HeJ mice (TLR4 deficient) and C3H/HeJ-SCID mice, but not C3H/OuJ mice (TLR4 intact), died after intraperitoneal infection with Leptospira interrogans serovar Icterohaemorrhagiae.

Molecular and cellular mechanisms of protective immunity to coccidioidomycosis.

Coccidioides immitis is endemic in the soil of the desert Southwest. It causes a respiratory infection that is usually mild, but can last months and may disseminate beyond the lung. Disseminated infections can be fatal or require life-long therapy.

Innate immunity to the pathogenic fungus Coccidioides posadasii is dependent on Toll-like receptor 2 and Dectin-1.

Coccidioides posadasii is a pathogenic fungus that causes endemic and epidemic coccidioidomycosis in the deserts of North, Central, and South America. How the innate immune system responds to the organism is not well understood. Here we show that elicited mouse peritoneal macrophages respond to spherules (the tissue form of the fungus) by producing proinflammatory cytokines as measured by quantitative PCR of cellular transcripts and by enzyme-linked immunosorbent assay (ELISA) assays for secreted protein.

Lipopolysaccharide (LPS)-binding protein inhibits responses to cell-bound LPS.

Lipopolysaccharide (LPS)-binding protein (LBP) is an acute phase reactant that may play a dual role in vivo, both potentiating and decreasing cell responses to bacterial LPS. Whereas low concentrations of LBP potentiate cell stimulation by transferring LPS to CD14, high LBP concentrations inhibit cell responses to LPS. One inhibitory mechanism involves the ability of LBP to neutralize LPS by transferring it to plasma lipoproteins, whereas other inhibitory mechanisms, such as the one described here, do not require exogenous lipoproteins.

Minimally modified LDL binds to CD14, induces macrophage spreading via TLR4/MD-2, and inhibits phagocytosis of apoptotic cells.

Minimally modified low density lipoprotein (mmLDL) is a pro-inflammatory and pro-atherogenic lipoprotein that, unlike profoundly oxidized LDL (OxLDL), is not recognized by scavenger receptors and thus does not have enhanced uptake by macrophages. However, here we demonstrate that mmLDL (as well as OxLDL) induces actin polymerization and spreading of macrophages, which results in such pro-atherogenic consequences as inhibition of phagocytosis of apoptotic cells but enhancement of OxLDL uptake. We also demonstrate for the first time that the lipopolysaccharide receptor, CD14, and toll-like receptor-4/MD-2 are involved in these mmLDL effects.