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 Mass Spectrometry-Based Proteomics of Fungal Pathogenesis, Host–Fungal Interactions, and Antifungal Development

2019 ◽  
Vol 5 (2) ◽  
pp. 52 ◽  
Author(s):  
Brianna Ball ◽  
Arianne Bermas ◽  
Duncan Carruthers-Lay ◽  
Jennifer Geddes-McAlister
Keyword(s):  
Mass Spectrometry ◽  
Fungal Pathogens ◽  
Molecular Mechanisms ◽  
Fungal Infections ◽  
Treatment Options ◽  
Drug Efficacy ◽  
Global Scale ◽  
Fungal Pathogenesis ◽  
Biological Targets ◽  
Fungal Interactions

The prevalence of fungal diseases is increasing on a global scale, ranging from acute to systemic infections caused by commensal or pathogenic microorganisms, often associated with the immune status of the host. Morbidity and mortality rates remain high and our ability to treat fungal infections is challenged by a limited arsenal of antifungal agents and the emergence of drug resistant pathogens. There is a high demand for new approaches to elucidate the fungal mechanisms of pathogenesis and the interplay between host and pathogen to discover novel treatment options. Moreover, the need for improved drug efficacy and reduced host toxicity requires the identification and characterization of antifungal biological targets and molecular mechanisms of action. Mass spectrometry (MS)-based proteomics is a rapidly advancing field capable of addressing these priorities by providing comprehensive information on the dynamics of cellular processes, modifications, and interactions. In this Review, we focus on applications of MS-based proteomics in a diverse array of fungal pathogens and host systems to define and distinguish the molecular details of fungal pathogenesis and host–fungal interactions. We also explore the emerging role of MS-based proteomics in the discovery and development of novel antifungal therapies and provide insight into the future of MS-based proteomics in fungal biology.

scholarly journals Oxidative Stress as a Possible Target in the Treatment of Toxoplasmosis: Perspectives and Ambiguities

2021 ◽  
Vol 22 (11) ◽  
pp. 5705
Author(s):  
Karolina Szewczyk-Golec ◽  
Marta Pawłowska ◽  
Roland Wesołowski ◽  
Marcin Wróblewski ◽  
Celestyna Mila-Kierzenkowska
Keyword(s):  
Oxidative Stress ◽  
Animal Studies ◽  
Treatment Options ◽  
Natural Antioxidants ◽  
Redox Status ◽  
Host Cells ◽  
Common Disease ◽  
Parasite Viability

Toxoplasma gondii is an apicomplexan parasite causing toxoplasmosis, a common disease, which is most typically asymptomatic. However, toxoplasmosis can be severe and even fatal in immunocompromised patients and fetuses. Available treatment options are limited, so there is a strong impetus to develop novel therapeutics. This review focuses on the role of oxidative stress in the pathophysiology and treatment of T. gondii infection. Chemical compounds that modify redox status can reduce the parasite viability and thus be potential anti-Toxoplasma drugs. On the other hand, oxidative stress caused by the activation of the inflammatory response may have some deleterious consequences in host cells. In this respect, the potential use of natural antioxidants is worth considering, including melatonin and some vitamins, as possible novel anti-Toxoplasma therapeutics. Results of in vitro and animal studies are promising. However, supplementation with some antioxidants was found to promote the increase in parasitemia, and the disease was then characterized by a milder course. Undoubtedly, research in this area may have a significant impact on the future prospects of toxoplasmosis therapy.

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.

scholarly journals Emerging Fungal Infections: New Patients, New Patterns, and New Pathogens

2019 ◽  
Vol 5 (3) ◽  
pp. 67 ◽  
Author(s):  
Friedman ◽  
Schwartz
Keyword(s):  
North America ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Trichophyton Mentagrophytes ◽  
Invasive Fungal Disease ◽  
Multidrug Resistant ◽  
Antifungal Prophylaxis ◽  
Candida Spp ◽  
Sporothrix Brasiliensis ◽  
Emerging Fungal Infections

: The landscape of clinical mycology is constantly changing. New therapies for malignant and autoimmune diseases have led to new risk factors for unusual mycoses. Invasive candidiasis is increasingly caused by non-albicans Candida spp., including C. auris, a multidrug-resistant yeast with the potential for nosocomial transmission that has rapidly spread globally. The use of mould-active antifungal prophylaxis in patients with cancer or transplantation has decreased the incidence of invasive fungal disease, but shifted the balance of mould disease in these patients to those from non-fumigatus Aspergillus species, Mucorales, and Scedosporium/Lomentospora spp. The agricultural application of triazole pesticides has driven an emergence of azole-resistant A. fumigatus in environmental and clinical isolates. The widespread use of topical antifungals with corticosteroids in India has resulted in Trichophyton mentagrophytes causing recalcitrant dermatophytosis. New dimorphic fungal pathogens have emerged, including Emergomyces, which cause disseminated mycoses globally, primarily in HIV infected patients, and Blastomyces helicus and B. percursus, causes of atypical blastomycosis in western parts of North America and in Africa, respectively. In North America, regions of geographic risk for coccidioidomycosis, histoplasmosis, and blastomycosis have expanded, possibly related to climate change. In Brazil, zoonotic sporotrichosis caused by Sporothrix brasiliensis has emerged as an important disease of felines and people.

scholarly journals Antimicrobial resistance among fungi from patients with urinary tract infections in Ojo, Lagos, Nigeria

2021 ◽  
Vol 14 (03) ◽  
pp. 254-264
Author(s):  
Dauphin Dighitoghi Moro ◽  
Oluwole Moses David
Keyword(s):  
Urinary Tract ◽  
Amphotericin B ◽  
Urinary Tract Infections ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Candida Spp ◽  
Fungal Isolates ◽  
Vaginal Swabs ◽  
Tract Infections

The incidence of fungal urinary tract infections has risen gradually and has thus constituted a public health challenge. The aim of this study was to determine the prevalence of urinary tract infections by fungi in two health centres in Ojo, Lagos. A total of 200 patients attending the health centers constituting 160 males’ urines and 40 females’ vaginal swabs were recruited for this study. Midstream urine samples and vaginal swabs were aseptically collected and processed using standard mycological techniques. Fungal isolates were identified based on cultural characteristics, lactophenol blue stain, chlamydospore formation, colony colour on CHROM agar Candida medium and API yeast identification. Antifungal susceptibility testing of the isolates was performed by using the Broth dilution and Kirby-Bauer disk diffusion methods using two of the most commonly used antifungal agents. A total of 122 fungal isolates, of which 68 (55.7%) were Candida spp. and 54(44.3%) Aspergillus spp. were recovered. The Candida spp. included 64 (52.5%) C. albicans and 4(3.3%) C. glabrata while Aspergillus spp. included A. flavus, 20(16.4%), A. fumigatus, 24 (19.8%) and A niger, 10(8.2%). The most common fungal pathogens in the urinary tracts of the subjects were Candida albicans and Aspergillus fumigatus. Both C. albicans and A. fumigatus were highly susceptible to both fluconazole and amphotericin B in dimethyl sulphoxide and water (90-100%). Similarly, all Aspergillus spp. were susceptible to both antifungals except A. flavus which showed a slight resistance (10-15%), which appears to be emerging. Both fluconazole and amphotericin B still show high chances of therapeutic efficacy against fungal infections of the urinary tracts.

scholarly journals Fungal Infection in Lung Transplantation

2021 ◽  
Vol 42 (03) ◽  
pp. 471-482
Author(s):  
Cassie C. Kennedy ◽  
Kelly M. Pennington ◽  
Elena Beam ◽  
Raymund R. Razonable
Keyword(s):  
Fungal Infection ◽  
Fungal Pathogens ◽  
Lung Transplant ◽  
Fungal Infections ◽  
Treatment Strategies ◽  
Invasive Fungal Infections ◽  
Molecular Diagnostic ◽  
Candida Spp ◽  
Diagnostic Strategies ◽  
Culture Techniques

AbstractInvasive fungal infections threaten lung transplant outcomes with high associated morbidity and mortality. Pharmacologic prophylaxis may be key to prevent posttransplant invasive fungal infections, but cost, adverse effects, and absorption issues are barriers to effective prophylaxis. Trends in fungal infection diagnostic strategies utilize molecular diagnostic methodologies to complement traditional histopathology and culture techniques. While lung transplant recipients are susceptible to a variety of fungal pathogens, Candida spp. and Aspergillus spp. infections remain the most common. With emerging resistant organisms and multiple novel antifungal agents in the research pipeline, it is likely that treatment strategies will continue to evolve.

scholarly journals StuA-Regulated Processes in the Dermatophyte Trichophyton rubrum: Transcription Profile, Cell-Cell Adhesion, and Immunomodulation

2021 ◽  
Vol 11 ◽  
Author(s):  
Tamires A. Bitencourt ◽  
João Neves-da-Rocha ◽  
Maira P. Martins ◽  
Pablo R. Sanches ◽  
Elza A. S. Lang ◽  
...  
Keyword(s):  
Cell Wall ◽  
Transcription Factors ◽  
Fungal Pathogens ◽  
Trichophyton Rubrum ◽  
Fungal Infections ◽  
Critical Role ◽  
Cell Interaction ◽  
Substantial Impact ◽  
Fungal Host ◽  
Cell Cell

Fungal infections represent a significant concern worldwide, contributing to human morbidity and mortality. Dermatophyte infections are among the most significant mycoses, and Trichophyton rubrum appears to be the principal causative agent. Thus, an understanding of its pathophysiology is urgently required. Several lines of evidence have demonstrated that the APSES family of transcription factors (Asm1p, Phd1p, Sok2p, Efg1p, and StuA) is an important point of vulnerability in fungal pathogens and a potential therapeutic target. These transcription factors are unique to fungi, contributing to cell differentiation and adaptation to environmental cues and virulence. It has recently been demonstrated that StuA plays a pleiotropic role in dermatophyte pathophysiology. It was suggested that it functions as a mediator of crosstalk between different pathways that ultimately contribute to adaptive responses and fungal-host interactions. The complex regulation of StuA and its interaction pathways are yet to be unveiled. Thus, this study aimed to gain a deeper understanding of StuA-regulated processes in T. rubrum by assessing global gene expression following growth on keratin or glucose sources. The data showed the involvement of StuA in biological processes related to central carbon metabolism and glycerol catabolism, reactive oxygen species metabolism, and cell wall construction. Changes in carbohydrate metabolism may be responsible for the significant alteration in cell wall pattern and consequently in cell-cell interaction and adhesion. Loss of StuA led to impaired biofilm production and promoted proinflammatory cytokine secretion in a human keratinocyte cell line. We also observed the StuA-dependent regulation of catalase genes. Altogether, these data demonstrate the multitude of regulatory targets of StuA with a critical role in central metabolism that may ultimately trigger a cascade of secondary effects with substantial impact on fungal physiology and virulence traits.

Fungal infections in solid organ transplantation

2017 ◽  
Author(s):  
Darius Armstrong James ◽  
Anand Shah ◽  
Anna Reed
Keyword(s):  
Organ Transplantation ◽  
Fungal Infections ◽  
Wide Spectrum ◽  
Treatment Options ◽  
Solid Organ Transplantation ◽  
Invasive Disease ◽  
Global Scale ◽  
Molecular Diagnostic ◽  
Individual Risk ◽  
Solid Organ

Fungal infections are a significant and life-threatening complication of organ transplantation, on a global scale. Risk varies according to transplant type, with liver, lung, and small bowel transplant recipients being at particular risk. Whilst invasive candidiasis is the most common fungal infection in organ transplantation overall, aspergillosis is a particular problem in lung transplantation. In addition, a wide spectrum of fungi may cause invasive disease in organ transplantation, consequently diagnosis and treatment can be challenging. Key challenges are to understand individual risk for infection, appropriate prophylactic strategies, and molecular diagnostic approaches. Treatment options are complicated by drug–drug interactions with transplant therapy, as well as intrinsic allograft dysfunction seen in many patients. In this chapter, we review the epidemiology, risk factors, diagnosis, and management of fungal infections in solid organ transplantation.

Opportunistic Fungal Infection

Chest Imaging ◽  
2019 ◽  
pp. 209-213
Author(s):  
Sonia L. Betancourt
Keyword(s):  
Fungal Infection ◽  
Opportunistic Infection ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Hematologic Malignancy ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Candida Spp ◽  
Common Opportunistic Infection ◽  
Cryptococcus Spp

Opportunistic fungal infections are caused by fungi that are nonpathogenic in the immunocompetent host, many of which are part of the normal upper respiratory tract flora. These organisms may cause pulmonary infection in immunocompromised hosts. Immunocompromised patients and patients with febrile neutropenia with opportunistic fungal infections may have normal chest radiographs. Thus, chest CT should be performed for further evaluation. Imaging abnormalities in this patient population should raise suspicion for opportunistic infection. Neutropenia is the single most important risk factor for Aspergillosis. Aspergillus is the most common opportunistic infection in patients with hematologic malignancy and bone marrow transplantation. Aspergillus spp., Candida spp., and Cryptococcus spp. are the most common fungal infections in patients with solid organ transplantation. Pneumocystis jirovecii is the most common fungal infection in patients AIDS with CD4 count s<200 cells/mm3. Cryptococcal pneumonia is also common in this population. There has been a recent increase in uncommon fungal pathogens causing invasive pulmonary disease.

scholarly journals Epigenetic Mechanisms of Inflammasome Regulation

2020 ◽  
Vol 21 (16) ◽  
pp. 5758 ◽  
Author(s):  
Giulia Poli ◽  
Consuelo Fabi ◽  
Marina Maria Bellet ◽  
Claudio Costantini ◽  
Luisa Nunziangeli ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Fungal Infections ◽  
Cell Damage ◽  
Epigenetic Mechanisms ◽  
Cpg Dna ◽  
Post Translational Modifications ◽  
Inflammatory Pathways ◽  
Complementary Mechanism

The innate immune system represents the host’s first-line defense against pathogens, dead cells or environmental factors. One of the most important inflammatory pathways is represented by the activation of the NOD-like receptor (NLR) protein family. Some NLRs induce the assembly of large caspase-1-activating complexes called inflammasomes. Different types of inflammasomes have been identified that can respond to distinct bacterial, viral or fungal infections; sterile cell damage or other stressors, such as metabolic imbalances. Epigenetic regulation has been recently suggested to provide a complementary mechanism to control inflammasome activity. This regulation can be exerted through at least three main mechanisms, including CpG DNA methylation, histones post-translational modifications and noncoding RNA expression. The repression or promotion of expression of different inflammasomes (NLRP1, NLRP2, NLRP3, NLRP4, NLRP6, NLRP7, NLRP12 and AIM2) through epigenetic mechanisms determines the development of pathologies with variable severity. For example, our team recently explored the role of microRNAs (miRNAs) targeting and modulating the components of the inflammasome as potential biomarkers in bladder cancer and during therapy. This suggests that the epigenetic control of inflammasome-related genes could represent a potential target for further investigations of molecular mechanisms regulating inflammatory pathways.

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