scholarly journals Emerging Prospects for Combating Fungal Infections by Targeting Phosphatidylinositol Transfer Proteins

2021 ◽  
Vol 22 (13) ◽  
pp. 6754
Author(s):  
Danish Khan ◽  
Aaron H. Nile ◽  
Ashutosh Tripathi ◽  
Vytas A. Bankaitis
Keyword(s):  
Fungal Pathogens ◽  
Rational Design ◽  
Fungal Infections ◽  
Next Generation ◽  
Phosphoinositide Signaling ◽  
Lead Compounds ◽  
Response Capacity ◽  
Phosphatidylinositol Transfer ◽  
Anti Fungal ◽  
Phosphatidylinositol Transfer Proteins

The emergence of fungal “superbugs” resistant to the limited cohort of anti-fungal agents available to clinicians is eroding our ability to effectively treat infections by these virulent pathogens. As the threat of fungal infection is escalating worldwide, this dwindling response capacity is fueling concerns of impending global health emergencies. These developments underscore the urgent need for new classes of anti-fungal drugs and, therefore, the identification of new targets. Phosphoinositide signaling does not immediately appear to offer attractive targets due to its evolutionary conservation across the Eukaryota. However, recent evidence argues otherwise. Herein, we discuss the evidence identifying Sec14-like phosphatidylinositol transfer proteins (PITPs) as unexplored portals through which phosphoinositide signaling in virulent fungi can be chemically disrupted with exquisite selectivity. Recent identification of lead compounds that target fungal Sec14 proteins, derived from several distinct chemical scaffolds, reveals exciting inroads into the rational design of next generation Sec14 inhibitors. Development of appropriately refined next generation Sec14-directed inhibitors promises to expand the chemical weaponry available for deployment in the shifting field of engagement between fungal pathogens and their human hosts.

scholarly journals Role for IL-1 Family Cytokines in Fungal Infections

2021 ◽  
Vol 12 ◽  
Author(s):  
James S. Griffiths ◽  
Giorgio Camilli ◽  
Natalia K. Kotowicz ◽  
Jemima Ho ◽  
Jonathan P. Richardson ◽  
...  
Keyword(s):  
Fungal Pathogens ◽  
Fungal Infections ◽  
Systemic Disease ◽  
Severe Disease ◽  
Life Threatening ◽  
Current Therapies ◽  
Immunotherapy Target ◽  
Systemic Infections ◽  
Fungal Immunity ◽  
Anti Fungal

Fungal pathogens kill approximately 1.5 million individuals per year and represent a severe disease burden worldwide. It is estimated over 150 million people have serious fungal disease such as recurrent mucosal infections or life-threatening systemic infections. Disease can ensue from commensal fungi or new infection and involves different fungal morphologies and the expression of virulence factors. Therefore, anti-fungal immunity is complex and requires coordination between multiple facets of the immune system. IL-1 family cytokines are associated with acute and chronic inflammation and are essential for the innate response to infection. Recent research indicates IL-1 cytokines play a key role mediating immunity against different fungal infections. During mucosal disease, IL-1R and IL-36R are required for neutrophil recruitment and protective Th17 responses, but function through different mechanisms. During systemic disease, IL-18 drives protective Th1 responses, while IL-33 promotes Th2 and suppresses Th1 immunity. The IL-1 family represents an attractive anti-fungal immunotherapy target. There is a need for novel anti-fungal therapeutics, as current therapies are ineffective, toxic and encounter resistance, and no anti-fungal vaccine exists. Furthering our understanding of the IL-1 family cytokines and their complex role during fungal infection may aid the development of novel therapies. As such, this review will discuss the role for IL-1 family cytokines in fungal infections.

scholarly journals An Emerging Multi-Drug Resistant Yeast Like Fungus Candida auris Infections in ICUs

2020 ◽  
Vol 8 (02) ◽  
pp. 1-2
Author(s):  
Rajeshwar Reddy Kasarla
Keyword(s):  
Diabetes Mellitus ◽  
Bone Marrow ◽  
Drug Resistance ◽  
Fungal Pathogens ◽  
Metabolic Disorders ◽  
Fungal Infections ◽  
Drug Resistant ◽  
Candida Auris ◽  
Anti Fungal ◽  
Transplantation Procedures

 The incidence of fungal infections in recent years is increasing rapidly and there is an emergence of newer fungal pathogens and anti-fungal drug resistance due to multiple predisposing reasons such as prolonged and indiscriminate use of antibiotic therapy, immunosuppressive corticosteroid therapy, aggressive use of ant-cancer drugs, bone marrow and organ transplantation procedures, and underlying conditions like immunodeficiency diseases (E.g., AIDS) and metabolic disorders such as diabetes mellitus.

scholarly journals Drug utilisation and self medication pattern of anti-fungal drugs in dermatology outpatient department of a tertiary care hospital

2017 ◽  
Vol 6 (9) ◽  
pp. 2189
Author(s):  
Pooja Deb ◽  
Ipseeta Mohanty ◽  
Indu Slathia ◽  
Vandana Verma
Keyword(s):  
Fungal Pathogens ◽  
Fungal Infections ◽  
Symptomatic Relief ◽  
Tertiary Care ◽  
Fixed Dose ◽  
Care Practice ◽  
Care Hospital ◽  
Self Medication ◽  
Cross Sectional ◽  
Anti Fungal

Background: Fungal infections have become increasingly prevalent. Self-medication is a common health care practice to treat fungal diseases or for symptomatic relief. Because of self-medication drug-sensitive fungal pathogens have gradually developed resistance. Aims and objectives of the study was to define the pattern of antifungal drug use and self-medication pattern for common fungal infections of skin in dermatology outpatient.Methods: The present study was an Observational, descriptive, cross sectional study conducted at Dermatology OPD of MGM Medical College, Kamothe. All adult patients with fungal infections of the skin attending the Dermatology OPD were enrolled. A study performa was specifically designed to record information related to demographic, disease profile and medications prescribed.Results: A total of 200 patient’s prescriptions were analysed. Percentage of drugs prescribed by generic name was found to be 20.26%, Percentage of drugs prescribed from National Essential Drug List 2015 was found to be 79.74%. There were no encounters with antibiotic and parenteral preparations. Only 5.16% of the drugs prescribed were fixed dose combination (FDC) as compared to 94.93% as Monotherapy. Most frequently prescribed anti-fungal agents were the azoles; amongst which Imidazoles (53.33%) were the commonest. Most commonly prescribed individual antifungal was oral Terbinafine (64.81%) and topical was Eberconazole (58.49%). The dosage form most frequently encountered was Cream (92.45%). The prevalence of self-medication for dermatological conditions among patients was 62.26%. Most of the drugs for self-medication were topical (creams) FDC of antifungal and steroids. Around 78% of the self-medication information was obtained from the chemists.Conclusions: The study documented physician preference for Monotherapy than FDC. Prescribers need to be made aware for prescribing generic and essential drugs, thus ensuring rational utilization. They also need to counsel and discourage patients from self-medication.

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.

Rational design on materials for developing next generation lithium-ion secondary battery

2020 ◽  
pp. 100298
Author(s):  
Arun Mambazhasseri Divakaran ◽  
Manickam Minakshi ◽  
Parisa Arabzadeh Bahri ◽  
Shashi Paul ◽  
Pooja Kumari ◽  
...  
Keyword(s):  
Rational Design ◽  
Lithium Ion ◽  
Next Generation ◽  
Secondary Battery

Phosphatidylinositol transfer proteins and protein kinase C make separate but non-interacting contributions to the phosphorylation state necessary for secretory competence in rat mast cells

2001 ◽  
Vol 356 (1) ◽  
pp. 287-296 ◽  
Author(s):  
Jef A. PINXTEREN ◽  
Bastien D. GOMPERTS ◽  
Danise ROGERS ◽  
Scott E. PHILLIPS ◽  
Peter E. R. TATHAM ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Mast Cells ◽  
Protein Kinase ◽  
Aminoglycoside Antibiotic ◽  
Pleckstrin Homology Domain ◽  
Kinase C ◽  
Streptolysin O ◽  
Regulatory Machinery ◽  
Phosphatidylinositol Transfer ◽  
Phosphatidylinositol Transfer Proteins

Mast cells permeabilized by streptolysin O undergo exocytosis when stimulated with Ca2+ and guanosine 5′-[γ-thio]triphosphate but become progressively refractory to this stimulus if it is delayed. This run-down of responsiveness occurs over a period of 20–30min, during which the cells leak soluble and tethered proteins. We show here that withdrawal of ATP during the process of run-down is strongly inhibitory but that as little as 25μM ATP can extend responsiveness significantly; this effect is maximal at 50μM. When phosphatidylinositol transfer proteins (PITPs) are provided to cells at the time of permeabilization, run-down is retarded. We conclude that in the presence of ATP they convey substrates for phosphorylation that are essential for exocytosis and thus interact with the regulatory machinery. Furthermore, we show that PITPα and PITPβ have additive effects in this mechanism, suggesting that they are not functionally redundant. Alternatively, secretion from run-down cells can be inhibited by the aminoglycoside antibiotic neomycin, which is understood to bind to phosphoinositide headgroups, and by a PH (pleckstrin homology) domain polypeptide that binds phosphoinositides. The apparent displacement of neomycin by exogenous PITPs suggests that these proteins screen essential lipids. Secretion from run-down cells is also inhibited by 1-O-hexadecyl-2-O-methyl-rac-glycerol (AMG-C16), an inhibitor of protein kinase C. The lack of synergy between neomycin and AMG-C16 suggests that protein kinase C independently provides a second essential component through protein phosphorylation and that there are two independent phosphorylation pathways necessary for secretion competence.

Sign in / Sign up

Export Citation Format

Share Document