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

Cheng, Kuang-Ting; Wu, Chih-Lung; Yip, Bak-Sau; Chih, Ya-Han; Peng, Kuang-Li; Hsu, Su-Ya; Yu, Huiyuan; Cheng, Jya‐Wei

doi:10.3390/ijms21072654

Cited by 27 publications

(11 citation statements)

References 30 publications

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“…Recently, AMPs have attracted great interests due to their broad-spectrum antimicrobial activities, low toxicity, small molecules, and low weight cationic peptides (Bosch and Zasloff, 2021). To date, many AMPs have been isolated and characterized for their antifungal activity (Lázár et al, 2018;Aguiar et al, 2020;Cheng et al, 2020). Today, more than 3,000 AMPs have been found in different AMP databases, while only a few peptide-based drugs are available in the market and/or preclinical stage (Seyedjavadi et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

A Cecropin-4 Derived Peptide C18 Inhibits Candida albicans by Disturbing Mitochondrial Function

et al. 2022

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Global burden of fungal infections and related health risk has accelerated at an incredible pace, and multidrug resistance emergency aggravates the need for the development of new effective strategies. Candida albicans is clinically the most ubiquitous pathogenic fungus that leads to high incidence and mortality in immunocompromised patients. Antimicrobial peptides (AMPs), in this context, represent promising alternatives having potential to be exploited for improving human health. In our previous studies, a Cecropin-4-derived peptide named C18 was found to possess a broader antibacterial spectrum after modification and exhibit significant antifungal activity against C. albicans. In this study, C18 shows antifungal activity against C. albicans or non-albicans Candida species with a minimum inhibitory concentration (MIC) at 4∼32 μg/ml, and clinical isolates of fluconazole (FLZ)-resistance C. tropicalis were highly susceptible to C18 with MIC = 4∼32 μg/ml. Additionally, C18 is superior to FLZ for killing planktonic C. albicans from inhibitory and killing kinetic curves. Moreover, C18 could attenuate the virulence of C. albicans, which includes damaging the cell structure, retarding hyphae transition, and inhibiting biofilm formation. Intriguingly, in the Galleria mellonella model with C. albicans infection, C18 could improve the survival rate of G. mellonella larvae to 70% and reduce C. albicans load from 5.01 × 107 to 5.62 × 104 CFU. For mechanistic action of C18, the level of reactive oxygen species (ROS) generation and cytosolic Ca2 + increased in the presence of C18, which is closely associated with mitochondrial dysfunction. Meanwhile, mitochondrial membrane potential (△Ψm) loss and ATP depletion of C. albicans occurred with the treatment of C18. We hypothesized that C18 might inhibit C. albicans via triggering mitochondrial dysfunction driven by ROS generation and Ca2 + accumulation. Our observation provides a basis for future research to explore the antifungal strategies and presents C18 as an attractive therapeutic candidate to be developed to treat candidiasis.

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Section: Introductionmentioning

confidence: 99%

A Cecropin-4 Derived Peptide C18 Inhibits Candida albicans by Disturbing Mitochondrial Function

et al. 2022

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“…The initial association of cationic AMPs with anionic bilayers is mostly directed by electrostatic interactions due to their net charge being opposed to that of the target membrane (von Deuster and Knecht, 2011;Alvares et al, 2017). Therefore, the presence of cations can significantly reduce the antifungal activity of AMPs, as demonstrated in case of e.g., AFP, coprisin (dung beetle), DmAMP1, HNP-1, HsAFP1, indolicidin (cattle), NaD1, OefDef1.1, P113 (a 12-amino-acid fragment of histatin 5), RsAFP2, and hBD-1,-2 (Figures 2C-E; Osborn et al, 1995;Goldman et al, 1997;Bals et al, 1998;Edgerton et al, 2000;Lee et al, 2003Lee et al, , 2012Lee et al, , 2014Theis et al, 2003;Bleackley et al, 2019;Li et al, 2019;Cheng et al, 2020). Similarly, in yeast mutants lacking Agp2p, a plasma membrane regulator of polyamine and carnitine transport, the antifungal activity of NaD1 is significantly reduced.…”

Section: Influence Of Cations On the Initial Association Of Amps Withmentioning

confidence: 86%

Membrane-Interacting Antifungal Peptides

Struyfs

Cammue

Thevissen

2021

Front. Cell Dev. Biol.

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The incidence of invasive fungal infections is increasing worldwide, resulting in more than 1.6 million deaths every year. Due to growing antifungal drug resistance and the limited number of currently used antimycotics, there is a clear need for novel antifungal strategies. In this context, great potential is attributed to antimicrobial peptides (AMPs) that are part of the innate immune system of organisms. These peptides are known for their broad-spectrum activity that can be directed toward bacteria, fungi, viruses, and/or even cancer cells. Some AMPs act via rapid physical disruption of microbial cell membranes at high concentrations causing cell leakage and cell death. However, more complex mechanisms are also observed, such as interaction with specific lipids, production of reactive oxygen species, programmed cell death, and autophagy. This review summarizes the structure and mode of action of antifungal AMPs, thereby focusing on their interaction with fungal membranes.

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“…The decrease in antifungal activity due to interferents presents in saliva environment, as well as the already existing resistance of the fungus to the peptide, requires new strategies for the improvement of Hst5 antifungal activity. Among such strategies are the synthesis of Hst5 fragments and the development of metal complexes formed with the peptide, which could increase the activity against C. albicans [36][37][38][39][40][41][42].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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

Cited by 27 publications

References 30 publications

A Cecropin-4 Derived Peptide C18 Inhibits Candida albicans by Disturbing Mitochondrial Function

A Cecropin-4 Derived Peptide C18 Inhibits Candida albicans by Disturbing Mitochondrial Function

Membrane-Interacting Antifungal Peptides

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

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