scholarly journals Host Defense Peptides as Templates for Antifungal Drug Development

2020 ◽  
Vol 6 (4) ◽  
pp. 241
Author(s):  
Virginia Basso ◽  
Dat Q. Tran ◽  
André J. Ouellette ◽  
Michael E. Selsted
Keyword(s):  
Host Defense ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Multidrug Resistant ◽  
Current Treatment ◽  
Antifungal Drugs ◽  
Antifungal Drug ◽  
Host Defense Peptides ◽  
Invasive Fungal Diseases ◽  
Defense Peptides

Current treatment for invasive fungal diseases is limited to three classes of antifungal drugs: azoles, polyenes, and echinocandins. The most recently introduced antifungal class, the echinocandins, was first approved nearly 30 years ago. The limited antifungal drug portfolio is rapidly losing its clinical utility due to the inexorable rise in the incidence of invasive fungal infections and the emergence of multidrug resistant (MDR) fungal pathogens. New antifungal therapeutic agents and novel approaches are desperately needed. Here, we detail attempts to exploit the antifungal and immunoregulatory properties of host defense peptides (HDPs) in the design and evaluation of new antifungal therapeutics and discuss historical limitations and recent advances in this quest.

scholarly journals Current and Potential Applications of Host-Defense Peptides and Proteins in Urology

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Joey Chor Yee Lo ◽  
Dirk Lange
Keyword(s):  
Host Defense ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Biological Molecules ◽  
Host Defense Peptides ◽  
Promising Alternative ◽  
Cellular Processes ◽  
Potential Applications ◽  
Defense Peptides ◽  
Bacterial Cell Membrane

The use of antibiotics has become increasingly disfavored as more multidrug resistant pathogens are on the rise. A promising alternative to the use of these conventional drugs includes antimicrobial peptides or host-defense peptides. These peptides typically consist of short amino acid chains with a net cationic charge and a substantial portion of hydrophobic residues. They mainly target the bacterial cell membrane but are also capable of translocating through the membrane and target intracellular components, making it difficult for bacteria to gain resistance as multiple essential cellular processes are being targeted. The use of these peptides in the field of biomedical therapies has been examined, and the different approaches to using them under various settings are constantly being discovered. In this review, we discuss the current and potential applications of these host-defense peptides in the field of urology. Besides the use of these peptides as antimicrobial agents, the value of these biological molecules has recently been expanded to their use as antitumor and anti-kidney-stone agents.

scholarly journals Host Defense Peptides: Dual Antimicrobial and Immunomodulatory Action

2021 ◽  
Vol 22 (20) ◽  
pp. 11172
Author(s):  
Matthew Drayton ◽  
Julia P. Deisinger ◽  
Kevin C. Ludwig ◽  
Nigare Raheem ◽  
Anna Müller ◽  
...  
Keyword(s):  
Host Defense ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Health Concern ◽  
Rapid Rise ◽  
Host Defense Peptides ◽  
Viable Solution ◽  
Defense Peptides ◽  
Immunomodulatory Action ◽  
Direct Killing

The rapid rise of multidrug-resistant (MDR) bacteria has once again caused bacterial infections to become a global health concern. Antimicrobial peptides (AMPs), also known as host defense peptides (HDPs), offer a viable solution to these pathogens due to their diverse mechanisms of actions, which include direct killing as well as immunomodulatory properties (e.g., anti-inflammatory activity). HDPs may hence provide a more robust treatment of bacterial infections. In this review, the advent of and the mechanisms that lead to antibiotic resistance will be described. HDP mechanisms of antibacterial and immunomodulatory action will be presented, with specific examples of how the HDP aurein 2.2 and a few of its derivatives, namely peptide 73 and cG4L73, function. Finally, resistance that may arise from a broader use of HDPs in a clinical setting and methods to improve biocompatibility will be briefly discussed.

Update on Candida krusei, a potential multidrug-resistant pathogen

2020 ◽  
Vol 59 (1) ◽  
pp. 14-30 ◽  
Author(s):  
A T Jamiu ◽  
J Albertyn ◽  
O M Sebolai ◽  
C H Pohl
Keyword(s):  
Water Solubility ◽  
Fungal Infections ◽  
Current Knowledge ◽  
Hematologic Malignancy ◽  
Multidrug Resistant ◽  
Candida Krusei ◽  
Antifungal Resistance ◽  
Antifungal Drugs ◽  
Antifungal Drug ◽  
Intrinsic Resistance

Abstract Although Candida albicans remains the main cause of candidiasis, in recent years a significant number of infections has been attributed to non-albicans Candida (NAC) species, including Candida krusei. This epidemiological change can be partly explained by the increased resistance of NAC species to antifungal drugs. C. krusei is a diploid, dimorphic ascomycetous yeast that inhabits the mucosal membrane of healthy individuals. However, this yeast can cause life-threatening infections in immunocompromised patients, with hematologic malignancy patients and those using prolonged azole prophylaxis being at higher risk. Fungal infections are usually treated with five major classes of antifungal agents which include azoles, echinocandins, polyenes, allylamines, and nucleoside analogues. Fluconazole, an azole, is the most commonly used antifungal drug due to its low host toxicity, high water solubility, and high bioavailability. However, C. krusei possesses intrinsic resistance to this drug while also rapidly developing acquired resistance to other antifungal drugs. The mechanisms of antifungal resistance of this yeast involve the alteration and overexpression of drug target, reduction in intracellular drug concentration and development of a bypass pathway. Antifungal resistance menace coupled with the paucity of the antifungal arsenal as well as challenges involved in antifungal drug development, partly due to the eukaryotic nature of both fungi and humans, have left researchers to exploit alternative therapies. Here we briefly review our current knowledge of the biology, pathophysiology and epidemiology of a potential multidrug-resistant fungal pathogen, C. krusei, while also discussing the mechanisms of drug resistance of Candida species and alternative therapeutic approaches.

scholarly journals A Nanoemulsion as an Effective Treatment Against Human Pathogenic Fungi

2019 ◽  
Author(s):  
Alexis Garcia ◽  
Yong Yi Fan ◽  
Sandeep Vellanki ◽  
Eun Young Huh ◽  
DiFernando Vanegas ◽  
...  
Keyword(s):  
Fungal Pathogens ◽  
Fungal Infections ◽  
Healing Process ◽  
Pathogenic Fungi ◽  
Multidrug Resistant ◽  
Antifungal Drugs ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Development Of Resistance

AbstractThe emergence of immunocompromising diseases such as HIV/AIDS or other immunosuppressive medical conditions have opened an opportunity for fungal infections to afflict patients globally. An increase antifungal drug resistant fungi have posed a serious threat to patients. Combining these circumstances with a limited variety of antifungal drugs available to treat patients has left us in a situation where we need to develop new therapeutic approaches that are less prone to development of resistance by pathogenic fungi. In this study we present the utilization of the nanoemulsion NB-201 to control human pathogenic fungi. We found that the NB-201 exhibited in vitro activity against C. albicans, including both planktonic growth and biofilms. Furthermore, treatments with NB-201 significantly reduced the fungal burden at the infection site and presented enhanced healing process after subcutaneous infections by multidrug resistant C. albicans in a murine host system. NB-201 also exhibited in vitro growth inhibition activity against other fungal pathogens, including Cryptococcus spp, Aspergillus fumigatus, and Mucorales. Due to the nature of the activity of this nanoemulsion, there is a minimized chance of drug resistance to develop, thus presents a novel treatment to control fungal wound or skin infections.

scholarly journals Linking Cellular Morphogenesis with Antifungal Treatment and Susceptibility in Candida Pathogens

2019 ◽  
Vol 5 (1) ◽  
pp. 17 ◽  
Author(s):  
Jehoshua Sharma ◽  
Sierra Rosiana ◽  
Iqra Razzaq ◽  
Rebecca Shapiro
Keyword(s):  
Drug Resistance ◽  
Candida Species ◽  
Cellular Response ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Antifungal Drug ◽  
Health Concern ◽  
Biofilm Growth ◽  
Antifungal Drug Resistance

Fungal infections are a growing public health concern, and an increasingly important cause of human mortality, with Candida species being amongst the most frequently encountered of these opportunistic fungal pathogens. Several Candida species are polymorphic, and able to transition between distinct morphological states, including yeast, hyphal, and pseudohyphal forms. While not all Candida pathogens are polymorphic, the ability to undergo morphogenesis is linked with the virulence of many of these pathogens. There are also many connections between Candida morphogenesis and antifungal drug treatment and susceptibility. Here, we review how Candida morphogenesis—a key virulence trait—is linked with antifungal drugs and antifungal drug resistance. We highlight how antifungal therapeutics are able to modulate morphogenesis in both sensitive and drug-resistant Candida strains, the shared signaling pathways that mediate both morphogenesis and the cellular response to antifungal drugs and drug resistance, and the connection between Candida morphology, drug resistance, and biofilm growth. We further review the development of anti-virulence drugs, and targeting Candida morphogenesis as a novel therapeutic strategy to target fungal pathogens. Together, this review highlights important connections between fungal morphogenesis, virulence, and susceptibility to antifungals.

Geographically Distinct Expression Profile of Host Defense Peptides in the Skin of the Chinese Odorous Frog, Odorrana margaretae

2014 ◽  
Vol 4 (4) ◽  
pp. 288-297
Author(s):  
LING Guiying ◽  
LI Li ◽  
GAO Jiuxiang ◽  
YU Haining ◽  
WANG Yipeng ◽  
...  
Keyword(s):  
Host Defense ◽  
Expression Profile ◽  
Host Defense Peptides ◽  
Defense Peptides

Human Host Defense Peptides - Role in Maintaining Human Homeostasis and Pathological Processes

2017 ◽  
Vol 24 (7) ◽  
pp. 654-672 ◽  
Author(s):  
Malgorzata Anna Dawgul ◽  
Katarzyna E. Greber ◽  
Wieslaw Sawicki ◽  
Wojciech Kamysz
Keyword(s):  
Host Defense ◽  
Host Defense Peptides ◽  
Human Host ◽  
Defense Peptides

scholarly journals Reinforcing the Immunocompromised Host Defense against Fungi: Progress beyond the Current State of the Art

2021 ◽  
Vol 7 (6) ◽  
pp. 451
Author(s):  
Georgios Karavalakis ◽  
Evangelia Yannaki ◽  
Anastasia Papadopoulou
Keyword(s):  
Host Defense ◽  
Hematopoietic Cell Transplantation ◽  
State Of The Art ◽  
Fungal Infections ◽  
Solid Organ Transplantation ◽  
Immunocompromised Host ◽  
Antifungal Drugs ◽  
Solid Organ ◽  
Cell Immunotherapy ◽  
Life Threatening

Despite the availability of a variety of antifungal drugs, opportunistic fungal infections still remain life-threatening for immunocompromised patients, such as those undergoing allogeneic hematopoietic cell transplantation or solid organ transplantation. Suboptimal efficacy, toxicity, development of resistant variants and recurrent episodes are limitations associated with current antifungal drug therapy. Adjunctive immunotherapies reinforcing the host defense against fungi and aiding in clearance of opportunistic pathogens are continuously gaining ground in this battle. Here, we review alternative approaches for the management of fungal infections going beyond the state of the art and placing an emphasis on fungus-specific T cell immunotherapy. Harnessing the power of T cells in the form of adoptive immunotherapy represents the strenuous protagonist of the current immunotherapeutic approaches towards combating invasive fungal infections. The progress that has been made over the last years in this field and remaining challenges as well, will be discussed.

scholarly journals Mechanistic Fingerprinting Reveals Kinetic Signatures of Resistance to Daptomycin and Host Defense Peptides in Streptococcus mitis-oralis

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 404
Author(s):  
Michael R. Yeaman ◽  
Liana C. Chan ◽  
Nagendra N. Mishra ◽  
Arnold S. Bayer
Keyword(s):  
Flow Cytometry ◽  
Host Defense ◽  
Durable Resistance ◽  
Cross Resistance ◽  
Streptococcus Mitis ◽  
Host Defense Peptides ◽  
Strain Pair ◽  
Defense Peptides

Streptococcus mitis-oralis (S. mitis-oralis) infections are increasingly prevalent in specific populations, including neutropenic cancer and endocarditis patients. S. mitis-oralis strains have a propensity to evolve rapid, high-level and durable resistance to daptomycin (DAP-R) in vitro and in vivo, although the mechanism(s) involved remain incompletely defined. We examined mechanisms of DAP-R versus cross-resistance to cationic host defense peptides (HDPs), using an isogenic S. mitis-oralis strain-pair: (i) DAP-susceptible (DAP-S) parental 351-WT (DAP MIC = 0.5 µg/mL), and its (ii) DAP-R variant 351-D10 (DAP MIC > 256 µg/mL). DAP binding was quantified by flow cytometry, in-parallel with temporal (1–4 h) killing by either DAP or comparative prototypic cationic HDPs (hNP-1; LL-37). Multicolor flow cytometry was used to determine kinetic cell responses associated with resistance or susceptibility to these molecules. While overall DAP binding was similar between strains, a significant subpopulation of 351-D10 cells hyper-accumulated DAP (>2–4-fold vs. 351-WT). Further, both DAP and hNP-1 induced cell membrane (CM) hyper-polarization in 351-WT, corresponding to significantly greater temporal DAP-killing (vs. 351-D10). No strain-specific differences in CM permeabilization, lipid turnover or regulated cell death were observed post-exposure to DAP, hNP-1 or LL-37. Thus, the adaptive energetics of the CM appear coupled to the outcomes of interactions of S. mitis-oralis with DAP and selected HDPs. In contrast, altered CM permeabilization, proposed as a major mechanism of action of both DAP and HDPs, did not differentiate DAP-S vs. DAP-R phenotypes in this S. mitis-oralis strain-pair.

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