Antifungal properties of 5-hydroxytryptamine (serotonin) against Candida species in vitro

Abstract Background Multidrug resistant Candida is an increasing concern. C. parapsilosis in particular has decreased in vitro susceptibility to echinocandins. As a result, fluconazole had been favored for C. parapsilosis treatment. However, there is growing concern about increasing azole resistance among Candida species. We report on antifungal susceptibility patterns of C. parapsilosis in the US from 2008 through 2018. Methods Active, population-based surveillance for candidemia through the Centers for Disease Control and Prevention’s (CDC) Emerging Infections Program was conducted between 2008–2018, eventually encompassing 9 states (GA, MD,OR, TN, NY, CA, CO, MN, NM). Each incident isolate was sent to the CDC for species confirmation and antifungal susceptibility testing (AFST). Frequency of resistance was calculated and stratified by year and state using SAS 9.4 Results Of the 8,704 incident candidemia isolates identified, 1,471 (15%) were C. parapsilosis; the third most common species after C. albicans and C. glabrata. AFST results were available for 1,340 C. parapsilosis isolates. No resistance was detected to caspofungin (MIC50 0.25) or micafungin (MIC50 1.00) with only one (< 1%) isolate resistant to anidulafungin (MIC50 1.00). In contrast, 84 (6.3%) isolates were resistant to fluconazole and another 44 (3.3%) isolates had dose-dependent susceptibility to fluconazole (MIC50 1.00). Fluconazole resistance increased sharply from an average of 4% during 2008–2014 to a peak of 14% in 2016 with a subsequent decline to 6% in 2018 (see figure). Regional variation is also observed with fluconazole resistance ranging from 0% (CO, MN, NM) to 42% (NY) of isolates by site. Conclusion The recent marked increase in fluconazole resistance among C. parapsilosis highlights this pathogen as an emerging drug resistant pathogen of concern and the need for ongoing antifungal resistance surveillance among Candida species. Our data support the empiric use of echinocandins for C. parapsilosis bloodstream infections and underscore the need to obtain AFST prior to fluconazole treatment. Furthermore, regional variation in fluconazole resistance emphasizes the importance of understanding local Candida susceptibility patterns. Disclosures Lee Harrison, MD, GSK (Consultant)Merck (Consultant)Pfizer (Consultant)Sanofi Pasteur (Consultant)

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Review of T-2307, an Investigational Agent That Causes Collapse of Fungal Mitochondrial Membrane Potential

Journal of Fungi ◽

10.3390/jof7020130 ◽

2021 ◽

Vol 7 (2) ◽

pp. 130

Author(s):

Nathan P. Wiederhold

Keyword(s):

Membrane Potential ◽

Mitochondrial Membrane Potential ◽

Candida Species ◽

Mammalian Cells ◽

Mitochondrial Membrane ◽

Fungal Infections ◽

Published Data ◽

Candida Auris

Invasive infections caused by Candida that are resistant to clinically available antifungals are of increasing concern. Increasing rates of fluconazole resistance in non-albicans Candida species have been documented in multiple countries on several continents. This situation has been further exacerbated over the last several years by Candida auris, as isolates of this emerging pathogen that are often resistant to multiple antifungals. T-2307 is an aromatic diamidine currently in development for the treatment of invasive fungal infections. This agent has been shown to selectively cause the collapse of the mitochondrial membrane potential in yeasts when compared to mammalian cells. In vitro activity has been demonstrated against Candida species, including C. albicans, C. glabrata, and C. auris strains, which are resistant to azole and echinocandin antifungals. Activity has also been reported against Cryptococcus species, and this has translated into in vivo efficacy in experimental models of invasive candidiasis and cryptococcosis. However, little is known regarding the clinical efficacy and safety of this agent, as published data from studies involving humans are not currently available.

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Symbiotic NCR Peptide Fragments Affect the Viability, Morphology and Biofilm Formation of Candida Species

International Journal of Molecular Sciences ◽

10.3390/ijms22073666 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3666

Author(s):

Bettina Szerencsés ◽

Attila Gácser ◽

Gabriella Endre ◽

Ildikó Domonkos ◽

Hilda Tiricz ◽

...

Keyword(s):

Candida Species ◽

Biofilm Formation ◽

Therapeutic Potential ◽

Fungal Infections ◽

Combined Treatment ◽

Antimicrobial Activities ◽

Dilution Method ◽

Model Legume ◽

Anticandidal Activity

The increasing rate of fungal infections causes global problems not only in human healthcare but agriculture as well. To combat fungal pathogens limited numbers of antifungal agents are available therefore alternative drugs are needed. Antimicrobial peptides are potent candidates because of their broad activity spectrum and their diverse mode of actions. The model legume Medicago truncatula produces >700 nodule specific cysteine-rich (NCR) peptides in symbiosis and many of them have in vitro antimicrobial activities without considerable toxicity on human cells. In this work we demonstrate the anticandidal activity of the NCR335 and NCR169 peptide derivatives against five Candida species by using the micro-dilution method, measuring inhibition of biofilm formation with the XTT (2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide) assay, and assessing the morphological change of dimorphic Candida species by microscopy. We show that both the N- and C-terminal regions of NCR335 possess anticandidal activity as well as the C-terminal sequence of NCR169. The active peptides inhibit biofilm formation and the yeast-hypha transformation. Combined treatment of C. auris with peptides and fluconazole revealed synergistic interactions and reduced 2-8-fold the minimal inhibitory concentrations. Our results demonstrate that shortening NCR peptides can even enhance and broaden their anticandidal activity and therapeutic potential.

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The antifungal activity of caspofungin in combination with antifungals or non-antifungals against Candida species in vitro and in clinical therapy

Expert Review of Anti-infective Therapy ◽

10.1080/14787210.2021.1941868 ◽

2021 ◽

Author(s):

Shan Su ◽

Haiying Yan ◽

Li Min ◽

Hongmei Wang ◽

Xueqi Chen ◽

...

Keyword(s):

Antifungal Activity ◽

Candida Species ◽

Clinical Therapy

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Dispersal of single and mixed non- albicans Candida species biofilms by β-1,3-glucanase in vitro

Microbial Pathogenesis ◽

10.1016/j.micpath.2017.10.057 ◽

2017 ◽

Vol 113 ◽

pp. 342-347 ◽

Cited By ~ 6

Author(s):

Yulong Tan ◽

Matthias Leonhard ◽

Su Ma ◽

Doris Moser ◽

Berit Schneider-Stickler

Keyword(s):

Candida Species

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In vitro activities of the tetrazole VT-1161 compared with itraconazole and fluconazole against Cryptococcus and non-albicans Candida species

Mycologia ◽

10.1080/00275514.2021.1913949 ◽

2021 ◽

pp. 1-8

Author(s):

Lili Wang ◽

Min Zhang ◽

Jian Guo ◽

Wenzheng Guo ◽

Ni Zhong ◽

...

Keyword(s):

Candida Species

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Anti-Candida Activity of Pomegranate Peel Extract in Comparison with Curcumin Extract and their Synergism with Fluconazole and Nystatin

10.51429/ejmm30212 ◽

2021 ◽

Vol 30 (2) ◽

pp. 81-87

Author(s):

Sara Y. Maxwell ◽

Sally Elnawasany ◽

Azza M. Hassan ◽

Marwa M. E. Abd-Elmonsef

Keyword(s):

Candida Species ◽

Synergistic Effects ◽

Systemic Disease ◽

Antifungal Drugs ◽

Diffusion Method ◽

Oropharyngeal Candidiasis ◽

Pomegranate Peel ◽

Methanolic Extracts ◽

Pomegranate Peel Extract

Background: Oropharyngeal candidiasis is an important sign that may reflect a serious systemic disease, especially in immunocompromised patients who face the intolerable side effects of the available antifungal drugs. This necessitates the development of safe and effective natural components. Objectives: to evaluate the in vitro activities of both pomegranate peel and curcumin extracts and to compare them with nystatin and fluconazole drugs against Candida species. As far as we know, this is the first study comparing between the antifungal potency of both extracts. Methodology: Different Candida species were isolated from patients with oropharyngeal candidiasis. The antifungal activities of methanolic extracts of pomegranate peel and curcumin were tested by disc diffusion method. Both extracts were added to each of nystatin and fluconazole discs to measure their synergistic effects. Results: Highly significant synergism was detected between both extracts and each of antifungal drugs. Curcumin extract was more potent than pomegranate extract. Conclusion: When used in combination with nystatin and fluconazole, curcumin and pomegranate peel extracts are promising and effective anti-Candida agents.

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