Hydrothermal Assisted Biogenic Synthesis of Silver Nanoparticles And Their Anticandidal Activity On Virulent Candida Isolates From COVID-19 Patients

Till now the exact mechanism and effect of biogenic silver nanoparticles on fungus is an indefinable question. To focus on this issue, we prepared hydrothermal assisted thyme coated silver nanoparticles (T/AgNPs) and their toxic effect on Candida isolates is described. The role of thyme (Thymus Vulgaris) in the reduction of silver ions and stabilization of T/AgNPs are estimated by Fourier transforms infrared spectroscopy, structure and size of present silver nanoparticles were detected via atomic force microscopy as well as high-resolution transmission electron microscopy. The biological activity of T/AgNPs was observed against Candida isolates from COVID-19 Patients. Testing of virulence of Candida species using Multiplex PCR. T/AgNPs proved highly effective against Candida albicans, Candida kruzei, Candida glabrata and MIC values ranging from 156.25 to 1,250 µg/mL and MFC values ranging from 312.5 to 5,000 µg/mL. The structural and morphological modifications due to T/AgNPs on Candida albicans were detected by TEM. It was highly observed that when Candida albicans cells were subjected to 50 and 100 µg/mL T/AgNPs, a remarkable change in the cell wall and cell membrane was observed.

Isocarpine as A New Peperidine Alkaloid From Adenocarpus Complicatus With Anticandidal Activity

Aims: Isolation of Isocarpine From Adenocarpus Complicatus. Background: Adenocarpus Complicatus L. is one of Adenocarpus genus which has about 50 species, from Fabaceae (Papilionaceae) family. This plant found in the Mediterranean basin as southern west part of Europe and North Afric forestes. Objective: Isolation of Isocarpine From Adenocarpus Complicatus as Anticandidal Agent method: A new piperidine alkaloid Isocarpine was isolated from the aerial parts of Adenocarpus Complicatus L., which gross in Syria. The structure of the new compound was determined by UV, IR, EI-Ms, 1H-NMR, 13C-NMR, DEPT-135, DQF-COSY and HMQC. Results: The anticandidal activity of isocarpine was screened against 38 Candida strains and showed remarkable inhibitory effect compared with fluconazole as antifungal reference drug. Conclusion: Isocarpine is antifungal agent.

Antifungal Activity of Linear and Disulfide-Cyclized Ultrashort Cationic Lipopeptides Alone and in Combination with Fluconazole against Vulvovaginal Candida spp.

Vulvovaginal candidiasis (VVC) occurs in over 75% of women at least once during their lifetime and is an infection that significantly affects their health. Candida strains resistant to standard azole antifungal therapy and relapses of VVC are more and more common. Hypothetically, biofilm is one of the main reasons of relapses and failure of the therapy. Ultrashort cationic lipopeptides (USCLs) exhibit high antimicrobial activities. Our previous study on USCLs revealed that disulfide cyclization can result in selective antifungal compounds. Therefore, four USCL were selected and their antifungal activity were studied on 62 clinical strains isolated from VVC. The results confirmed previous premises that cyclic analogs have increased selectivity between fungal cells and keratinocytes and improved anticandidal activity compared to their linear analogs against both planktonic and biofilm cultures. On the other hand, linear lipopeptides in combination with fluconazole showed a synergistic effect. It was found that the minimum inhibitory concentrations of the tested compounds in combination with fluconazole were at least four times lower than when used separately. Our results indicate that combination therapy of VVC with USCLs and fluconazole at low non-toxic concentrations can be beneficial owing to the synergistic effect. However, further in vivo studies are needed to confirm this hypothesis.

Antifungal Activity of Linear and Disulfide-Cyclized Ultrashort Cationic Lipopeptides Alone and in Combination with Fluconazole Against Vulvovaginal Candida spp.

Vulvovaginal candidiasis (VVC) occurs in over 75% of women at least once during their lifetime and is an infection that significantly affects their health. Candida strains resistant to standard azole antifungal therapy and relapses of VVC are more and more common. Hypothetically, biofilm is one of the main reasons of relapses and failure of the therapy. Ultrashort cationic lipopeptides (USCLs) exhibit high antimicrobial activities. Our previous study on USCLs revealed that disulfide cyclization can result in selective antifungal compounds. Therefore, four USCL were selected and their antifungal activity were studied on 62 clinical strains isolated from VVC. The results showed that cyclic analogs have increased selectivity between fungal cells and keratinocytes and improved anticandidal activity than their linear analogs against both planktonic and biofilm cultures. On the other hand, linear lipopeptides in combination with fluconazole showed the synergistic effect. It was found that the minimum inhibitory concentrations of the tested compounds in combination with fluconazole were at least four times lower than when used separately. Our results indicate that combination therapy of VVC with USCLs and fluconazole at low non-toxic concentrations can be beneficial owing to the synergistic effect. However, further in vivo studies are needed to confirm this hypothesis.

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

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.

Anticandidal Activity of Omiganan and Its Retro Analog Alone and in Combination with Fluconazole

Vulvovaginal candidiasis (VVC) is a vaginal infection that manifests itself as several symptoms which can lead to various life-threatening complications. The majority of VVC is caused by Candida albicans strains, and it is estimated that approximately 75% of women worldwide would suffer from this condition at least once during their lifetime. Surprisingly, the detailed pathomechanism of yeast-like fungi invasions in vagina is not yet fully understood. However, the ability to form biofilm on vaginal mucosa is considered as one of the critical factors associated with failure of the therapy and recurrences of the disease. Antimicrobial peptides (AMPs) are a promising class of compounds that are receiving a growing interest owing to their antibacterial, antifungal, and antibiofilm properties. Omiganan is a synthetic analog of Indolicidin that is characterized by wide spectrum of antimicrobial and antibiofilm activities. Recent reports suggest improved activity of analogs with a reversed sequence (retro-analog concept). Therefore, Omiganan and its retro analog were tested against planktonic forms and biofilm of 18 Candida strains isolated from VVC. Moreover, the synergy between the AMPs and fluconazole was studied as well. The AMPs appeared to be effective against C. albicans biofilm, and the reversion of the sequence generally led to an improved antimicrobial activity. Furthermore, confocal and scanning electron microscopic visualizations revealed the effectiveness of AMPs-fluconazole combinations also against fluconazole-resistant strains. Graphical Abstract