scholarly journals Effects of histatin 5 modifications on antifungal activity and kinetics of proteolysis

2019 ◽  
Vol 29 (2) ◽  
pp. 480-493 ◽  
Author(s):  
Svetlana P. Ikonomova ◽  
Parisa Moghaddam‐Taaheri ◽  
Yan Wang ◽  
Mary T. Doolin ◽  
Kimberly M. Stroka ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Histatin 5 ◽  
Kinetics Of

scholarly journals Synthetic Histidine-Rich Peptides Inhibit Candida Species and Other Fungi In Vitro: Role of Endocytosis and Treatment Implications

2006 ◽  
Vol 50 (8) ◽  
pp. 2797-2805 ◽  
Author(s):  
Jingsong Zhu ◽  
Paul W. Luther ◽  
Qixin Leng ◽  
A. James Mixson
Keyword(s):  
Nucleic Acid ◽  
Antifungal Activity ◽  
Antifungal Agents ◽  
Fungal Growth ◽  
Nucleic Acid Delivery ◽  
Histatin 5 ◽  
Ph Buffering ◽  
Endosomal Acidification

ABSTRACT A family of histidine-rich peptides, histatins, is secreted by the parotid gland in mammals and exhibits marked inhibitory activity against a number of Candida species. We were particularly interested in the mechanism by which histidine-rich peptides inhibit fungal growth, because our laboratory has synthesized a variety of such peptides for drug and nucleic acid delivery. In contrast to naturally occurring peptides that are linear, peptides made on synthesizers can be varied with respect to their degrees of branching. Using this technology, we explored whether histidine-lysine (HK) polymers of different complexities and degrees of branching affect the growth of several species of Candida. Polymers with higher degrees of branching were progressively more effective against Candida albicans, with the four-branched polymer, H2K4b, most effective. Furthermore, H2K4b accumulated efficiently in C. albicans, which may indicate its ability to transport other antifungal agents intracellularly. Although H2K4b had greater antifungal activity than histatin 5, their mechanisms were similar. Toxicity in C. albicans induced by histatin 5 or branched HK peptides was markedly reduced by 4,4′-diisothiocyanato-stilbene-2,2′-disulfonate, an inhibitor of anion channels. We also determined that bafilomycin A1, an inhibitor of endosomal acidification, significantly decreased the antifungal activity of H2K4b. This suggests that the pH-buffering and subsequent endosomal-disrupting properties of histidine-rich peptides have a role in their antifungal activity. Moreover, the ability of the histidine component of these peptides to disrupt endosomes, which allows their escape from the lysosomal pathway, may explain why these peptides are both effective antifungal agents and nucleic acid delivery carriers.

scholarly journals Antifungal activity of histatin-5 against non-albicans Candida species

2001 ◽  
Vol 16 (4) ◽  
pp. 250-252 ◽  
Author(s):  
H. Nikawa ◽  
C. Jin ◽  
H. Fukushima ◽  
S. Makihira ◽  
T. Hamada
Keyword(s):  
Antifungal Activity ◽  
Candida Species ◽  
Histatin 5

scholarly journals Antifungal Activity and Action Mechanism of Histatin 5-Halocidin Hybrid Peptides against Candida ssp

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0150196 ◽  
Author(s):  
Juhye Han ◽  
Md. Anirban Jyoti ◽  
Ho-Yeon Song ◽  
Woong Sik Jang
Keyword(s):  
Antifungal Activity ◽  
Action Mechanism ◽  
Histatin 5 ◽  
Hybrid Peptides

Use of a modified hair strand test to assess the antifungal activity kinetics of dog hair after a 2% climbazole shampoo application

2016 ◽  
Vol 27 (3) ◽  
pp. 148-e38 ◽  
Author(s):  
Jean Yanique Petit ◽  
Paola Cavana ◽  
Sandra Thoumire ◽  
Jacques Guillot ◽  
Sébastien Perrot
Keyword(s):  
Antifungal Activity ◽  
Hair Strand ◽  
Kinetics Of

scholarly journals The Interactions between the Antimicrobial Peptide P-113 and Living Candida albicans Cells Shed Light on Mechanisms of Antifungal Activity and Resistance

2020 ◽  
Vol 21 (7) ◽  
pp. 2654 ◽  
Author(s):  
Kuang-Ting Cheng ◽  
Chih-Lung Wu ◽  
Bak-Sau Yip ◽  
Ya-Han Chih ◽  
Kuang-Li Peng ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Antimicrobial Peptide ◽  
Oral Candidiasis ◽  
Immune Deficiency Syndrome ◽  
Deficiency Syndrome ◽  
Salivary Protein ◽  
Histatin 5 ◽  
C Terminus

In the absence of proper immunity, such as in the case of acquired immune deficiency syndrome (AIDS) patients, Candida albicans, the most common human fungal pathogen, may cause mucosal and even life-threatening systemic infections. P-113 (AKRHHGYKRKFH), an antimicrobial peptide (AMP) derived from the human salivary protein histatin 5, shows good safety and efficacy profiles in gingivitis and human immunodeficiency virus (HIV) patients with oral candidiasis. However, little is known about how P-113 interacts with Candida albicans or its degradation by Candida-secreted proteases that contribute to the fungi’s resistance. Here, we use solution nuclear magnetic resonance (NMR) methods to elucidate the molecular mechanism of interactions between P-113 and living Candida albicans cells. Furthermore, we found that proteolytic cleavage of the C-terminus prevents the entry of P-113 into cells and that increasing the hydrophobicity of the peptide can significantly increase its antifungal activity. These results could help in the design of novel antimicrobial peptides that have enhanced stability in vivo and that can have potential therapeutic applications.

scholarly journals Roles of Cellular Respiration, CgCDR1, and CgCDR2 in Candida glabrata Resistance to Histatin 5

2006 ◽  
Vol 50 (3) ◽  
pp. 1100-1103 ◽  
Author(s):  
Eva J. Helmerhorst ◽  
Caterina Venuleo ◽  
Dominique Sanglard ◽  
Frank G. Oppenheim
Keyword(s):  
Antifungal Activity ◽  
Broad Spectrum ◽  
Candida Glabrata ◽  
Efflux Pumps ◽  
Salivary Protein ◽  
Cellular Respiration ◽  
Fluconazole Resistance ◽  
Histatin 5

ABSTRACT Histatin 5, a human salivary protein with broad-spectrum antifungal activity, is remarkably ineffective against Candida glabrata. Fluconazole resistance in this fungus is due in most cases to upregulation of CgCDR efflux pumps. We investigated whether the distinct resistance of C. glabrata to histatin 5 is related to similar mechanisms.

scholarly journals Time-Kill Kinetics of Rezafungin (CD101) in Vagina-Simulative Medium for Fluconazole-Susceptible and Fluconazole-ResistantCandida albicansand Non-albicans CandidaSpecies

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Jeffrey B. Locke ◽  
Amanda L. Almaguer ◽  
Joanna L. Donatelli ◽  
Ken F. Bartizal
Keyword(s):  
Antifungal Activity ◽  
Fungicidal Activity ◽  
Susceptibility Testing ◽  
Inhibitory Concentration ◽  
The Novel ◽  
Testing Conditions ◽  
Fluconazole Resistant ◽  
Time Kill ◽  
Kinetics Of

Background.While echinocandins demonstrate excellent efficacy againstCandidaspecies in disseminated infections and demonstrate potent minimal inhibitory concentration (MIC) values under standard susceptibility testing conditions, investigation under conditions relevant to the vaginal environment was needed. We assessed the antifungal activity and time-kill kinetics of the novel echinocandin rezafungin (formerly CD101) under such conditions, againstCandidaspecies relevant to vulvovaginal candidiasis (VVC).Methods. Susceptibility testing of fluconazole-susceptible and fluconazole-resistantC. albicans,C. glabrata,C. tropicalis,C. parapsilosis, andC. kruseiwas performed in RPMI at pH 7.0 and in vagina-simulative medium (VSM) at pH 4.2 for topical rezafungin, terconazole, fluconazole, and amphotericin B. Time-kill kinetics were evaluated for rezafungin and terconazole at 2, 8, 32, and 128 μg/ml over 72 hours.Results.Rezafungin MIC values were the same or 2-fold higher in VSM/pH 4.2 versus RPMI/pH 7.0. SomeC. albicansterconazole MIC values were lower, but most were significantly higher in VSM than in RPMI. Rezafungin was fungicidal against 11/14 strains and near-fungicidal against the others. Terconazole (128 μg/ml) was fungicidal againstC. kruseiand near-fungicidal against susceptibleC. parapsilosisbut fungistatic versus all other strains evaluated.Conclusion.Rezafungin retained anti-Candidaactivity and fungicidal activity under in vitro conditions relevant to VVC.

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