scholarly journals Actual problems of mycoses caused by dimorphic pathogens

2021 ◽  
Author(s):  
A. Lipnitsky ◽  
N. Polovets ◽  
R. Surkova ◽  
O. Shergina ◽  
D. Victorov ◽  
...  
Keyword(s):  
Fungal Pathogens ◽  
Climate Changes ◽  
New Genus ◽  
Histoplasma Capsulatum ◽  
Fungal Infections ◽  
Alternative Hypothesis ◽  
Dust Storms ◽  
Coccidioides Immitis ◽  
Global Spread ◽  
Tissue Form

The literature review focuses on actual problems of the particularly dangerous mycoses – coccidioidomycosis, histoplasmosis, blastomycosis, paracoccidioidomycosis. The review presents modern data on the global spread of these fungal infections. Planetary climate changes widen the endemic areas of particularly dangerous mycoses by increase of the inhalational exposure of soil after dust storms, earthquakes and floodings. The prevaling view on the life cycle of agents of coccidioidomycosis (Coccidioides immitis, C.posadasii) is that these fungi dwell in soil (are saprobes) and so for them human and small-mammal fauna are only accidental hosts. The new alternative hypothesis implies that tissue form (spherule) of Coccidioides spp. lives in host granulomas of small mammals and transforms into spore producing hyphae when the animal host dies. It is demonstrated that Histoplasma capsulatum contains at least four different cryptic species, that differ genetically and express different virulence. Recently, discoveries of novel dimorphic systemic fungal pathogens have challenged the current taxonomy of family Ajellomycetacae. The new genus Emergomyces including five species is described. Another dimorphic pathogen is discovered and named Blastomyces percursus. These fungi cause disseminated mycoses globally, primarily in HIVinfected patients.

Fungal Opportunistic Infections in HIV Disease

2006 ◽  
Vol 19 (1) ◽  
pp. 17-30 ◽  
Author(s):  
Melody L. Duffalo
Keyword(s):  
Highly Active Antiretroviral Therapy ◽  
Fungal Pathogens ◽  
Histoplasma Capsulatum ◽  
Opportunistic Infections ◽  
Fungal Infections ◽  
Hiv Disease ◽  
Highly Active ◽  
Immunocompromised Individual ◽  
Fungal Organisms ◽  
Advanced Hiv Disease

Fungal pathogens can lead to many of the complications seen in advanced HIV disease and are commonly identified in HIV-infected populations with decreased immune function. Common fungal organisms affecting individuals with AIDS include Cryptococcus neoformans, various Candida species, and Histoplasma capsulatum. While infection with these organisms can be fatal, appropriate identification and management of the condition can result in reduced mortality and the opportunity for effectivemanagement of HIV disease with highly active antiretroviral therapy. This article describes the clinical presentation and treatment of 3 fungal infections common in the immunocompromised individual with AIDS. Current antifungal therapy for themanagement of these infections is discussed. In addition, the role of newer antifungal agents in the setting of these conditions is reviewed.

scholarly journals Evolution of the Mating Type Locus: Insights Gained from the Dimorphic Primary Fungal Pathogens Histoplasma capsulatum, Coccidioides immitis, and Coccidioides posadasii

2007 ◽  
Vol 6 (4) ◽  
pp. 622-629 ◽  
Author(s):  
James A. Fraser ◽  
Jason E. Stajich ◽  
Eric J. Tarcha ◽  
Garry T. Cole ◽  
Diane O. Inglis ◽  
...  
Keyword(s):  
Mating Type ◽  
Fungal Pathogens ◽  
Histoplasma Capsulatum ◽  
Type Systems ◽  
Coccidioides Immitis ◽  
Coccidioides Posadasii ◽  
Unique Region ◽  
Type Locus ◽  
Evolutionary Forces ◽  
Mating Type Locus

ABSTRACT Sexual reproduction of fungi is governed by the mating type (MAT) locus, a specialized region of the genome encoding key transcriptional regulators that direct regulatory networks to specify cell identity and fate. Knowledge of MAT locus structure and evolution has been considerably advanced in recent years as a result of genomic analyses that enable the definition of MAT locus sequences in many species as well as provide an understanding of the evolutionary plasticity of this unique region of the genome. Here, we extend this analysis to define the mating type locus of three dimorphic primary human fungal pathogens, Histoplasma capsulatum, Coccidioides immitis, and Coccidioides posadasii, using genomic analysis, direct sequencing, and bioinformatics. These studies provide evidence that all three species possess heterothallic bipolar mating type systems, with isolates encoding either a high-mobility-group (HMG) domain or an α-box transcriptional regulator. These genes are intact in all loci examined and have not been subject to loss or decay, providing evidence that the loss of fertility upon passage in H. capsulatum is not attributable to mutations at the MAT locus. These findings also suggest that an extant sexual cycle remains to be defined in both Coccidioides species, in accord with population genetic evidence. Based on these MAT sequences, a facile PCR test was developed that allows the mating type to be rapidly ascertained. Finally, these studies highlight the evolutionary forces shaping the MAT locus, revealing examples in which flanking genes have been inverted or subsumed and incorporated into an expanding MAT locus, allowing us to propose an expanded model for the evolution of the MAT locus in the phylum Ascomycota.

scholarly journals Post-Translational Modifications Drive Success and Failure of Fungal–Host Interactions

2021 ◽  
Vol 7 (2) ◽  
pp. 124
Author(s):  
Charmaine Retanal ◽  
Brianna Ball ◽  
Jennifer Geddes-McAlister
Keyword(s):  
Fungal Pathogens ◽  
Fungal Infections ◽  
Treatment Options ◽  
Global Scale ◽  
Host Cells ◽  
Candida Spp ◽  
Post Translational Modifications ◽  
Fungal Host ◽  
Resistant Species

Post-translational modifications (PTMs) change the structure and function of proteins and regulate a diverse array of biological processes. Fungal pathogens rely on PTMs to modulate protein production and activity during infection, manipulate the host response, and ultimately, promote fungal survival. Given the high mortality rates of fungal infections on a global scale, along with the emergence of antifungal-resistant species, identifying new treatment options is critical. In this review, we focus on the role of PTMs (e.g., phosphorylation, acetylation, ubiquitination, glycosylation, and methylation) among the highly prevalent and medically relevant fungal pathogens, Candida spp., Aspergillus spp., and Cryptococcus spp. We explore the role of PTMs in fungal stress response and host adaptation, the use of PTMs to manipulate host cells and the immune system upon fungal invasion, and the importance of PTMs in conferring antifungal resistance. We also provide a critical view on the current knowledgebase, pose questions key to our understanding of the intricate roles of PTMs within fungal pathogens, and provide research opportunities to uncover new therapeutic strategies.

scholarly journals Antifungal Efficacy of Marine Macroalgae against Fungal Isolates from Bronchial Asthmatic Cases

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 3032 ◽  
Author(s):  
Suresh Mickymaray ◽  
Wael Alturaiki
Keyword(s):  
Antifungal Activity ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Algal Species ◽  
Marine Macroalgae ◽  
Minimum Fungicidal Concentration ◽  
Asthmatic Patients ◽  
The Cost ◽  
Algal Extracts ◽  
Airway Colonization

Fungal sensitization is very common in bronchial asthmatic cases, and the connection with airway colonization by fungi remains uncertain. Antifungal therapy failure is a significant fraction of the cost and morbidity and mortality in the majority of the asthmatic cases. Hence, the present study aimed to investigate the antifungal activity of five marine macroalgae—Acanthaophora specifera, Cladophoropsis sp., Laurencia paniculata, Tydemania sp., and Ulva prolifera—which were tested on selected fungal pathogens isolated from 15 sputum of 45 bronchial asthmatic patients. The highest antifungal activity was observed in ethanol fractions of L. paniculata followed by U. prolifera, Cladophoropsis sp., A. specifera, and Tydemania sp. The minimum fungicidal concentration and minimum inhibitory concentration values of the ethanolic fractions of algal species were found to be 125–1000 µg/mL and 125–500 µg/mL, respectively. The algal extracts contained terpene alcohol, diterpene, steroids, sesquiterpene, and sesquiterpene alcohol, as determined by GC–MS/MS analyses. The present study shows that the marine macroalgae containing bioactive compounds had excellent inhibitory activity against a variety of fungal pathogens, which may be useful for combating fungal infections and recovering from chronic asthmatic states.

scholarly journals Lineage-specific selection and the evolution of virulence in the Candida clade

2021 ◽  
Vol 118 (12) ◽  
pp. e2016818118
Author(s):  
Sheena D. Singh-Babak ◽  
Tomas Babak ◽  
Hunter B. Fraser ◽  
Alexander D. Johnson
Keyword(s):  
Fungal Pathogens ◽  
Fungal Infections ◽  
Systemic Infection ◽  
Orthologous Gene ◽  
Regulatory Sequence ◽  
Mrna Levels ◽  
Evolutionary Changes ◽  
Interspecies Hybrids ◽  
Metabolism Enzymes ◽  
Evolution Of Virulence

Candida albicans is the most common cause of systemic fungal infections in humans and is considerably more virulent than its closest known relative, Candida dubliniensis. To investigate this difference, we constructed interspecies hybrids and quantified mRNA levels produced from each genome in the hybrid. This approach systematically identified expression differences in orthologous genes arising from cis-regulatory sequence changes that accumulated since the two species last shared a common ancestor, some 10 million y ago. We documented many orthologous gene-expression differences between the two species, and we pursued one striking observation: All 15 genes coding for the enzymes of glycolysis showed higher expression from the C. albicans genome than the C. dubliniensis genome in the interspecies hybrid. This pattern requires evolutionary changes to have occurred at each gene; the fact that they all act in the same direction strongly indicates lineage-specific natural selection as the underlying cause. To test whether these expression differences contribute to virulence, we created a C. dubliniensis strain in which all 15 glycolysis genes were produced at modestly elevated levels and found that this strain had significantly increased virulence in the standard mouse model of systemic infection. These results indicate that small expression differences across a deeply conserved set of metabolism enzymes can play a significant role in the evolution of virulence in fungal pathogens.

scholarly journals Sterol-response pathways mediate alkaline survival in diverse fungi

2020 ◽  
Author(s):  
Hannah E. Brown ◽  
Calla L. Telzrow ◽  
Joseph W. Saelens ◽  
Larissa Fernandes ◽  
J. Andrew Alspaugh
Keyword(s):  
Fungal Pathogens ◽  
Fungal Infections ◽  
Membrane Integrity ◽  
Microbial Pathogens ◽  
Alkaline Ph ◽  
Ph Response ◽  
Ph Tolerance ◽  
Alkaline Conditions ◽  
Host Infection ◽  
The Impact

AbstractThe ability for cells to maintain homeostasis in the presence of extracellular stress is essential for their survival. Stress adaptations are especially important for microbial pathogens to respond to rapidly changing conditions, such as those encountered during the transition from the environment to the infected host. Many fungal pathogens have acquired the ability to quickly adapt to changes in extracellular pH to promote their survival in the various micro-environments encountered during a host infection. For example, the fungal-specific Rim/Pal alkaline response pathway has been well characterized in many fungal pathogens, including Cryptococcus neoformans. However, alternative mechanisms for sensing and responding to host pH have yet to be extensively studied. Recent observations from a genetic screen suggest that the C. neoformans sterol homeostasis pathway is required for growth at elevated pH. This work explores interactions among mechanisms of membrane homeostasis, alkaline pH tolerance, and Rim pathway activation. We find that the sterol homeostasis pathway is necessary for growth in an alkaline environment, and that an elevated pH is sufficient to induce Sre1 activation. This pH-mediated activation of the Sre1 transcription factor is linked to the biosynthesis of ergosterol, but is not dependent on Rim pathway signaling, suggesting that these two pathways are responding to alkaline pH independently. Furthermore, we discover that C. neoformans is more susceptible to membrane-targeting antifungals in alkaline conditions highlighting the impact of micro-environmental pH on the treatment of invasive fungal infections. Together, these findings further connect membrane integrity and composition with the fungal pH response and pathogenesis.

scholarly journals Candida albicans Sterol C-14 Reductase, Encoded by the ERG24 Gene, as a Potential Antifungal Target Site

2002 ◽  
Vol 46 (4) ◽  
pp. 947-957 ◽  
Author(s):  
N. Jia ◽  
B. Arthington-Skaggs ◽  
W. Lee ◽  
C. A. Pierson ◽  
N. D. Lees ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Fungal Pathogens ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Brefeldin A ◽  
Agricultural Applications ◽  
Mouse Model System ◽  
Cellular Inhibitors ◽  
Germ Tubes ◽  
Doubling Times

ABSTRACT The incidence of fungal infections has increased dramatically, which has necessitated additional and prolonged use of the available antifungal agents. Increased resistance to the commonly used antifungal agents, primarily the azoles, has been reported, thus necessitating the discovery and development of compounds that would be effective against the major human fungal pathogens. The sterol biosynthetic pathway has proved to be a fertile area for antifungal development, and steps which might provide good targets for novel antifungal development remain. The sterol C-14 reductase, encoded by the ERG24 gene, could be an effective target for drug development since the morpholine antifungals, inhibitors of Erg24p, have been successful in agricultural applications. The ERG24 gene of Candida albicans has been isolated by complementation of a Saccharomyces cerevisiae erg24 mutant. Both copies of the C. albicans ERG24 gene have been disrupted by using short homologous regions of the ERG24 gene flanking a selectable marker. Unlike S. cerevisiae, the C. albicans ERG24 gene was not required for growth, but erg24 mutants showed several altered phenotypes. They were demonstrated to be slowly growing, with doubling times at least twice that of the wild type. They were also shown to be significantly more sensitive to an allylamine antifungal and to selected cellular inhibitors including cycloheximide, cerulenin, fluphenazine, and brefeldin A. The erg24 mutants were also slightly resistant to the azoles. Most importantly, erg24 mutants were shown to be significantly less pathogenic in a mouse model system and failed to produce germ tubes upon incubation in human serum. On the basis of these characteristics, inhibitors of Erg24p would be effective against C. albicans.

scholarly journals In Vitro Activities of Voriconazole, Itraconazole, and Amphotericin B against Blastomyces dermatitidis,Coccidioides immitis, and Histoplasma capsulatum

2000 ◽  
Vol 44 (6) ◽  
pp. 1734-1736 ◽  
Author(s):  
Ren-Kai Li ◽  
Meral A. Ciblak ◽  
Nicole Nordoff ◽  
Lester Pasarell ◽  
David W. Warnock ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Histoplasma Capsulatum ◽  
Clinical Laboratory ◽  
Lethal Effect ◽  
Blastomyces Dermatitidis ◽  
National Committee ◽  
Human Pathogens ◽  
Coccidioides Immitis ◽  
Dimorphic Fungi

ABSTRACT The in vitro activity of voriconazole was compared to those of itraconazole and amphotericin B against the mold forms of 304 isolates of three dimorphic fungi, Blastomyces dermatitidis,Coccidioides immitis, and Histoplasma capsulatum. MICs were determined by a broth microdilution adaptation of the National Committee for Clinical Laboratory Standards M27-A procedure. RPMI 1640 medium was used for tests with voriconazole and itraconazole, whereas Antibiotic Medium 3 with 2% glucose was used for amphotericin B. Minimum fungicidal concentrations (MFCs) were also determined. Amphotericin B was active against all three dimorphic fungi, with MICs at which 90% of the isolates tested are inhibited (MIC90s) of 0.5 to 1 μg/ml. Itraconazole had MIC90s of 0.06 μg/ml for H. capsulatum, 0.125 μg/ml for B. dermatitidis, and 1 μg/ml for C. immitis. The MIC90s of voriconazole were 0.25 μg/ml for all three fungi. Amphotericin B was fungicidal for B. dermatitidis and H. capsulatum with MFCs at which 90% of strains tested are killed (MFC90s) of 0.5 and 2 μg/ml, respectively. It was less active against C. immitis, with MFCs ranging from 0.5 to >16 μg/ml. Voriconazole and itraconazole were lethal for most isolates of B. dermatitidis, with MFC50s and MFC90s of 0.125 and 4 μg/ml, respectively. Both azoles were fungicidal for some isolates of H. capsulatum, with MFC50s of 2 and 8 μg/ml for itraconazole and voriconazole, respectively; neither had a lethal effect upon C. immitis. Our results suggest that voriconazole possesses promising activity against these important human pathogens.

Fungal Infection in Cystic Fibrosis

2021 ◽  
Vol 17 (2) ◽  
pp. 118-124
Author(s):  
Amirmehdi Sarvestani ◽  
Mohammad Almasian ◽  
Amirhossein Nafari
Keyword(s):  
Cystic Fibrosis ◽  
Fungal Infection ◽  
Fungal Pathogens ◽  
Respiratory Infections ◽  
Fungal Infections ◽  
Genetic Disorder ◽  
Medical Science ◽  
Resistant Species ◽  
Online Databases ◽  
New Treatments

Background: The prevalence of fungal infections has been increasing in recent years. Cystic fibrosis (CF) is a genetic disorder that affects organs such as the intestines, liver, pancreas, and especially the lungs. Introduction: Fungal pathogens are becoming a challenge in CF. Advanced medical science is associated with longer life expectancy in some patient groups. Method: A review was conducted on studies found on online databases, including Google Scholar, PubMed, and Scopus. Internet-based searches were performed on these databases for cystic fibrosis, respiratory infections, and fungal infection profiling to identify all relevant studies published between 2010 and 2020. Result: Fungal pathogens most frequently isolated from the respiratory tract include the Aspergillus genus, the Candida genus, Scedosporium apiospermum, and the Rasamsonia genus. In cystic fibrosis, these organisms usually colonize the respiratory and intestinal tracts and cause hypersensitivity responses and invasive diseases. Conclusion: Fungus-patient interactions are complicated and depend on various factors. Moreover, the emergence of drug-resistant species is a serious health issue, and the development of new treatments is crucial.

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