Effects of histatin 5 and derived peptides on Candida albicans

2001 ◽  
Vol 356 (2) ◽  
pp. 361-368 ◽  
Author(s):  
Anita L. A. RUISSEN ◽  
Jasper GROENINK ◽  
Eva J. HELMERHORST ◽  
Els WALGREEN-WETERINGS ◽  
Wim van't HOF ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Mitochondrial Membrane ◽  
Cytoplasmic Membrane ◽  
Human Saliva ◽  
Mitochondrial Activity ◽  
Complete Protection ◽  
Destructive Effect ◽  
Histatin 5 ◽  
Killing Activity ◽  
Anti Fungal

Three anti-microbial peptides were compared with respect to their killing activity against Candida albicans and their ability to disturb its cellular and internal membranes. Histatin 5 is an anti-fungal peptide occurring naturally in human saliva, while dhvar4 and dhvar5 are variants of its active domain, with increased anti-microbial activity. dhvar4has increased amphipathicity compared with histatin 5, whereas dhvar5has amphipathicity comparable with that of histatin 5. All three peptides caused depolarization of the cytoplasmic and/or mitochondrial membrane, indicating membranolytic activity. For the variant peptides both depolarization and killing occurred at a faster rate. With FITC-labelled peptides, no association with the cytoplasmic membrane was observed, contradicting the formation of permanent transmembrane multimeric peptide pores. Instead, the peptides were internalized and act on internal membranes, as demonstrated with mitochondrion- and vacuole-specific markers. In comparison with histatin 5, the variant peptides showed a more destructive effect on mitochondria. Entry of the peptides and subsequent killing were dependent on the metabolic state of the cells. Blocking of the mitochondrial activity led to complete protection against histatin 5 activity, whereas that of dhvar4 was hardly affected and that of dhvar5 was affected only intermediately.

scholarly journals Histatin 5 Metallopeptides and Their Potential against Candida albicans Pathogenicity and Drug Resistance

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1209
Author(s):  
Gabriela Vieira Silva Zolin ◽  
Fauller Henrique da Fonseca ◽  
Carolina Reis Zambom ◽  
Saulo Santesso Garrido
Keyword(s):  
Candida Albicans ◽  
Systemic Infection ◽  
Resistance Mechanisms ◽  
Human Saliva ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Correct Treatment ◽  
Histatin 5 ◽  
Effective Drugs ◽  
High Antifungal Activity

Usually caused by Candida albicans, buccal candidiasis begins with the morphological transition between yeast and hyphal cells. Over time and without the correct treatment, it can be disseminated through the bloodstream becoming a systemic infection with high mortality rates. C. albicans already shows resistance against antifungals commonly used in treatments. Therefore, the search for new drugs capable of overcoming antifungal resistance is essential. Histatin 5 (Hst5) is an antimicrobial peptide of the Histatin family, that can be found naturally in human saliva. This peptide presents high antifungal activity against C. albicans. However, Hst5 action can be decreased for interaction with enzymes and metal ions present in the oral cavity. The current work aims to bring a brief review of relevant aspects of the pathogenesis and resistance mechanisms already reported for C. albicans. In addition, are also reported here the main immune responses of the human body and the most common antifungal drugs. Finally, the most important aspects regarding Histatin 5 and the benefits of its interaction with metals are highlighted. The intention of this review is to show the promising use of Hst5 metallopeptides in the development of effective drugs.

scholarly journals Candida albicans Mutants Deficient in Respiration Are Resistant to the Small Cationic Salivary Antimicrobial Peptide Histatin 5

2000 ◽  
Vol 44 (2) ◽  
pp. 348-354 ◽  
Author(s):  
Csilla Gyurko ◽  
Urs Lendenmann ◽  
Robert F. Troxler ◽  
Frank G. Oppenheim
Keyword(s):  
Candida Albicans ◽  
Sodium Dodecyl ◽  
Atp Synthesis ◽  
Dependent Manner ◽  
Wild Type ◽  
Concentration Dependent Manner ◽  
Histatin 5 ◽  
Cellular Energy ◽  
Killing Activity ◽  
Petite Mutants

ABSTRACT Histatins are a group of small cationic peptides in human saliva which are well known for their antibacterial and antifungal activities. In a previous study we demonstrated that histatin 5 kills both blastoconidia and germ tubes of Candida albicans in a time- and concentration-dependent manner at 37°C, whereas no killing was detected at 4°C. This indicated that killing activity depends on cellular energy. To test histatin 5 killing activity at lower cellular ATP levels at 37°C, respiratory mutants, or so-called petite mutants, of C. albicans were prepared. These mutants are deficient in respiration due to mutations in mitochondrial DNA. Mutants were initially identified by their small colony size and were further characterized with respect to colony morphology, growth characteristics, respiratory activity, and cytochrome spectra. The killing activity of histatin 5 at the highest concentration was only 28 to 30% against respiratory mutants, whereas 98% of the wild-type cells were killed. Furthermore, histatin 5 killing activity was also tested on wild-type cells in the presence of the respiratory inhibitor sodium azide or, alternatively, the uncoupler carbonyl cyanidem-chlorophenylhydrazone. In both cases histatin 5 killing activity was significantly reduced. Additionally, supernatants and pellets of cells incubated with histatin 5 in the presence or absence of inhibitors of mitochondrial ATP synthesis were analyzed by sodium dodecyl sulfate gel electrophoresis. It was observed that wild-type cells accumulated large amounts of histatin 5, while wild-type cells treated with inhibitors or petite mutants did not accumulate significant amounts of the peptide. These data showed first that cellular accumulation of histatin 5 is necessary for killing activity and second that accumulation of histatin 5 depends on the availability of cellular energy. Therefore, mitochondrial ATP synthesis is required for effective killing activity of histatin 5.

scholarly journals Genomic instability induced by radiation-mimicking chemicals is not associated with persistent mitochondrial degeneration

2021 ◽  
Author(s):  
Luukkonen Jukka ◽  
Höytö Anne ◽  
Sokka Miiko ◽  
Syväoja Juhani ◽  
Juutilainen Jukka ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Ionizing Radiation ◽  
Genomic Instability ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Neuroblastoma Cells ◽  
Superoxide Production ◽  
Mitochondrial Activity ◽  
Mitochondrial Superoxide

AbstractIonizing radiation has been shown to cause induced genomic instability (IGI), which is defined as a persistently increased rate of genomic damage in the progeny of the exposed cells. In this study, IGI was investigated by exposing human SH-SY5Y neuroblastoma cells to hydroxyurea and zeocin, two chemicals mimicking different DNA-damaging effects of ionizing radiation. The aim was to explore whether IGI was associated with persistent mitochondrial dysfunction. Changes to mitochondrial function were assessed by analyzing mitochondrial superoxide production, mitochondrial membrane potential, and mitochondrial activity. The formation of micronuclei was used to determine immediate genetic damage and IGI. Measurements were performed either immediately, 8 days, or 15 days following exposure. Both hydroxyurea and zeocin increased mitochondrial superoxide production and affected mitochondrial activity immediately after exposure, and mitochondrial membrane potential was affected by zeocin, but no persistent changes in mitochondrial function were observed. IGI became manifested 15 days after exposure in hydroxyurea-exposed cells. In conclusion, immediate responses in mitochondrial function did not cause persistent dysfunction of mitochondria, and this dysfunction was not required for IGI in human neuroblastoma cells.

scholarly journals Anti-Fungal Activity of Cathelicidins and their Potential Role in Candida albicans Skin Infection

2005 ◽  
Vol 125 (1) ◽  
pp. 108-115 ◽  
Author(s):  
Belén López-García ◽  
Phillip H.A. Lee ◽  
Kenshi Yamasaki ◽  
Richard L. Gallo
Keyword(s):  
Candida Albicans ◽  
Potential Role ◽  
Skin Infection ◽  
Fungal Activity ◽  
Anti Fungal

scholarly journals Interactions between Terpinen-4-ol and Nystatin on biofilm of Candida albicans and Candida tropicalis

2018 ◽  
Vol 29 (4) ◽  
pp. 359-367 ◽  
Author(s):  
Caroline Coradi Tonon ◽  
Renata Serignoli Francisconi ◽  
Ester Alves Ferreira Bordini ◽  
Patrícia Milagros Maquera Huacho ◽  
Janaína de Cássia Orlandi Sardi ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Enzymatic Activity ◽  
Candida Tropicalis ◽  
Microtiter Plate ◽  
Synergistic Activity ◽  
Oral Keratinocytes ◽  
Mixed Species ◽  
Colony Forming Units ◽  
Anti Fungal ◽  
Oral Cells

Abstract The aim of this study was to evaluate the antifungal activity of Terpinen-4-ol associated with nystatin, on single and mixed species biofilms formed by Candida albicans and Candida tropicalis, as well as the effect of terpinen-4-ol on adhesion in oral cells and the enzymatic activity. The minimum inhibitory concentrations and minimum fungicide concentrations of terpinen-4-ol and nystatin on Candida albicans and Candida tropicalis were determined using the microdilution broth method, along with their synergistic activity (“checkerboard” method). Single and mixed species biofilms were prepared using the static microtiter plate model and quantified by colony forming units (CFU/mL). The effect of Terpinen-4-ol in adhesion of Candida albicans and Candida tropicalis in coculture with oral keratinocytes (NOK Si) was evaluated, as well as the enzymatic activity by measuring the size of the precipitation zone, after the growth agar to phospholipase, protease and hemolysin. Terpinen-4-ol (4.53 mg mL-1) and nystatin (0.008 mg mL-1) were able to inhibit biofilms growth, and a synergistic antifungal effect was showed with the drug association, reducing the inhibitory concentration of nystatin up to 8 times in single biofilm of Candida albicans, and 2 times in mixed species biofilm. A small decrease in the adhesion of Candida tropicalis in NOK Si cells was showed after treatment with terpinen-4-ol, and nystatin had a greater effect for both species. For enzymatic activity, the drugs showed no action. The effect potentiated by the combination of terpinen-4-ol and nystatin and the reduction of adhesion provide evidence of its potential as an anti-fungal agent.

scholarly journals Candida albicans exhibits distinct cytoprotective responses to anti-fungal drugs that facilitate the evolution of drug resistance

2020 ◽  
Author(s):  
V Bettauer ◽  
S Massahi ◽  
S Khurdia ◽  
ACBP Costa ◽  
RP Omran ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Candida Albicans ◽  
Drug Exposure ◽  
Fluorescent Imaging ◽  
Late Time ◽  
Transport Mechanisms ◽  
Short Term ◽  
Anti Fungal ◽  
Initial Drug

AbstractWe developed a modified protocol for nanolitre droplet-based single cell sequencing appropriate for fungal settings, and used it to transcriptionally profiled several thousands cells from a prototrophic Candida albicans population and several drug exposed colonies (incl. fluconazole, caspofungin and nystatin). Thousands of cells from each colony were profiled both at early and late time points post-treatment in order to infer survival trajectories from initial drug tolerance to drug resistance. We find that prototrophic C. albicans populations differentially and stochastically express cytoprotective epigenetic programs. For all drugs, there is evidence that tolerant individuals partition into distinct subpopulations, each with a unique survival strategy involving different regulatory programs. These responses are weakly related to changes in morphology (shift from white to opaque forms, or shift from yeast to filamentous forms). In turn, those subpopulations that successfully reach resistance each have a distinct multivariate epigenetic response that coordinates the expression of efflux pumps, chaperones, transport mechanisms, and cell wall maintenance. Live cell fluorescent imaging was used to validate predictions of which molecular responses most often led to survival after drug exposure. Together our findings provide evidence that C. albicans has a robust toolkit of short-term epigenetic cytoprotective responses designed to “buy time” and increase the chance of acquiring long-term resistance.

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