scholarly journals Novel Colloidal Nanocarrier of Cetylpyridinium Chloride: Antifungal Activities on Candida Species and Cytotoxic Potential on Murine Fibroblasts

2020 ◽  
Vol 6 (4) ◽  
pp. 218
Author(s):  
Heitor Ceolin Araujo ◽  
Laís Salomão Arias ◽  
Anne Caroline Morais Caldeirão ◽  
Lanay Caroline de Freitas Assumpção ◽  
Marcela Grigoletto Morceli ◽  
...  

Nanocarriers have been used as alternative tools to overcome the resistance of Candida species to conventional treatments. This study prepared a nanocarrier of cetylpyridinium chloride (CPC) using iron oxide nanoparticles (IONPs) conjugated with chitosan (CS), and assessed its antifungal and cytotoxic effects. CPC was immobilized on CS-coated IONPs, and the nanocarrier was physico-chemically characterized. Antifungal effects were determined on planktonic cells of Candida albicans and Candida glabrata (by minimum inhibitory concentration (MIC) assays) and on single- and dual-species biofilms of these strains (by quantification of cultivable cells, total biomass and metabolic activity). Murine fibroblasts were exposed to different concentrations of the nanocarrier, and the cytotoxic effect was evaluated by MTT reduction assay. Characterization methods confirmed the presence of a nanocarrier smaller than 313 nm. IONPs-CS-CPC and free CPC showed the same MIC values (0.78 µg mL−1). CPC-containing nanocarrier at 78 µg mL−1 significantly reduced the number of cultivable cells for all biofilms, surpassing the effect promoted by free CPC. For total biomass, metabolic activity, and cytotoxic effects, the nanocarrier and free CPC produced statistically similar outcomes. In conclusion, the IONPs-CS-CPC nanocarrier was more effective than CPC in reducing the cultivable cells of Candida biofilms without increasing the cytotoxic effects of CPC, and may be a useful tool for the treatment of oral fungal infections.

2021 ◽  
Vol 7 (7) ◽  
pp. 500
Author(s):  
Anne Caroline Morais Caldeirão ◽  
Heitor Ceolin Araujo ◽  
Laís Salomão Arias ◽  
Wilmer Ramírez Carmona ◽  
Gustavo Porangaba Miranda ◽  
...  

The contribution of different Candida species in oral fungal infections has stimulated the search for more effective therapies. This study assessed the antibiofilm effects of nanocarriers of miconazole (MCZ) or fluconazole (FLZ) on Candida biofilms, and their cytotoxic effects on murine fibroblasts. Three-species biofilms (Candida albicans/Candida glabrata/Candida tropicalis) were formed on 96-well plates, and they were treated with nanocarriers (iron oxide nanoparticles coated with chitosan—“IONPs-CS”) of MCZ or FLZ at 39/78/156 µg/mL; antifungals alone at 156 µg/mL and artificial saliva were tested as positive and negative controls, respectively. Biofilms were analyzed by colony forming units (CFU), biomass, metabolic activity, and structure/viability. The cytotoxicity (L929 cells) of all treatments was determined via 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) reduction assay. Data were submitted to one- or two-way ANOVA, followed by Tukey’s or Fisher LSD’s tests (p < 0.05). IONPs-CS-MCZ at 78 µg/mL promoted similar antibiofilm and cytotoxic effects compared with MCZ at 156 µg/mL. In turn, IONPs-CS-FLZ at 156 µg/mL was overall the most effective FLZ antibiofilm treatment, surpassing the effects of FLZ alone; this nanocarrier was also less cytotoxic compared with FLZ alone. It can be concluded that both nanocarriers are more effective alternatives to fight Candida biofilms compared with their respective positive controls in vitro, being a promising alternative for the treatment of oral fungal infections.


2020 ◽  
Vol 15 (4) ◽  
pp. 273-285 ◽  
Author(s):  
Taynara MT de Lima ◽  
Laís S Arias ◽  
Letícia F Afanaci ◽  
Raphael FB Ferraresse ◽  
Francisco N de S Neto ◽  
...  

Aim: To assemble, characterize and assess the antifungal effects of a new fluconazole (FLZ)-carrier nanosystem. Materials & methods: The nanosystem was prepared by loading FLZ on chitosan (CS)-coated iron oxide nanoparticles (IONPs). Antifungal effects were evaluated on planktonic cells (by minimum inhibitory concentration determination) and on biofilms (by quantification of cultivable cells, total biomass, metabolism and extracellular matrix) of Candida albicans and Candida glabrata. Results: Characterization results ratified the formation of a nanosystem (<320 nm) with FLZ successfully embedded. IONPs-CS-FLZ nanosystem reduced minimum inhibitory concentration values and, in general, showed similar antibiofilm effects compared with FLZ alone. Conclusion: IONPs-CS-FLZ nanosystem was more effective than FLZ mainly in inhibiting Candida planktonic cells. This nanocarrier has potential to fight fungal infections.


Pathogens ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 84
Author(s):  
Anderson França da Silva ◽  
Cláudia Quintino da Rocha ◽  
Luís Cláudio Nascimento da Silva ◽  
Alexsander Rodrigues Carvalho Júnior ◽  
Iven Neylla Farias Vale Mendes ◽  
...  

Vulvovaginal candidiasis is a common fungal infection in women. In this study, Platonia insignis hydroalcoholic extract (PiHE) and its fractions were evaluated for antifungal and antivirulence activities against vaginal Candida species. Dichloromethane (DCMF) and ethyl acetate fractions (EAF) obtained from PiHE effectively inhibited the pathogen. Electrospray ionization mass spectrometry was used for identifying the main compounds in extracts. Minimal inhibitory and fungicidal concentrations (MIC and MFC, respectively) were determined by a broth microdilution assay. Furthermore, we evaluated the effect of the extract and fractions on the virulence properties of Candida albicans, and their cytotoxicity effect was determined on RAW 264.7 cells. Compounds found in extracts were flavonoid glycosides, mainly derivatives of quercetin and myricetin. Extracts showed antifungal potential, with the lowest MIC value for EAF (1.3 mg/mL) and inhibited Candida adherence and biofilm formation. EAF disrupted 48 h biofilms with an inhibition rate of more than 90%. The extract and its fractions exhibited no cytotoxicity. The antifungal effects were attributed to the ability of these extracts to alter the mitochondrial membrane potential for the release of pro-apoptotic factors in the cytosol. In conclusion, our data suggest that PiHE and EAF could act as novel candidates for the development of new therapeutic treatments against fungal infections.


2021 ◽  
Vol 7 (2) ◽  
pp. 130
Author(s):  
Nathan P. Wiederhold

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.


2021 ◽  
Vol 22 (7) ◽  
pp. 3666
Author(s):  
Bettina Szerencsés ◽  
Attila Gácser ◽  
Gabriella Endre ◽  
Ildikó Domonkos ◽  
Hilda Tiricz ◽  
...  

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.


2021 ◽  
Vol 7 (6) ◽  
pp. 440
Author(s):  
Juan Vicente Mulet Bayona ◽  
Nuria Tormo Palop ◽  
Carme Salvador García ◽  
Begoña Fuster Escrivá ◽  
Mercedes Chanzá Aviñó ◽  
...  

In addition to the increase in fungal infections that has been observed in the last few decades, it has been reported that severe clinical COVID-19 can increase the risk of invasive fungal infections. The main objective of this study was to evaluate if there had been an increase in candidaemia and invasive pulmonary aspergillosis (IPA) cases since the onset of the SARS-CoV-2 pandemic. Data were retrospectively collected from April 2019 to March 2021, from patients admitted to Consorcio Hospital General Universitario de Valencia (Spain). A total of 152 candidaemia cases (56 of which were due to Candida auris) and 108 possible IPA cases were detected. A great increase in candidaemia cases was produced during the first and the third epidemic waves of the SARS-CoV-2 pandemic (June 2020, and January 2021, respectively), while an increase in IPA cases was produced during the third wave. The 28-day mortality rates in patients affected by candidaemia and IPA increased in 2020 and 2021. C. auris has displaced the other Candida species, becoming the most isolated Candida species in blood cultures since the onset of the SARS-CoV-2 pandemic. Antifungal consumption increased in 2020 when compared to 2019, especially echinocandins, voriconazole and isavuconazole.


2021 ◽  
Author(s):  
Rossana de Aguiar Cordeiro ◽  
Bruno Nascimento da Silva ◽  
Ana Luiza Ribeiro de Aguiar ◽  
Livia Maria Galdino Pereira ◽  
Fernando Victor Monteiro Portela ◽  
...  

Abstract Invasive fungal infections (IFIs) are important worldwide health problem, affecting the growing population of immunocompromised patients. Although the majority of IFIs are caused by Candida spp., other fungal species have been increasingly recognized as relevant opportunistic pathogens. Trichosporon spp. are members of skin and gut human microbiota. Since 1980’s, invasive trichosporonosis has been considered a significant cause of fungemia in patients with hematological malignancies. As prolonged antibiotic therapy is an important risk factor for IFIs, the present study investigated if vancomycin enhances growth and virulence of Trichosporon. Vancomycin was tested against T. inkin (n = 6) and T. asahii (n = 6) clinical strains. Planktonic cells were evaluated for their metabolic activity and virulence against Caenorhabditis elegans. Biofilms were evaluated for metabolic activity, biomass production, amphotericin B tolerance, induction of persister cells, and ultrastructure. Vancomycin stimulated planktonic growth of Trichosporon spp., increased tolerance to AMB, and potentiates virulence against C. elegans. Vancomycin stimulated growth (metabolic activity and biomass) of Trichosporon spp. biofilms during all stages of development. The antibiotic increased the number of persister cells inside Trichosporon biofilms. These cells showed higher tolerance to AMB than persister cells from VAN-free biofilms. Microscopic analysis showed that VAN increased production of extracellular matrix and cells in T. inkin and T. asahii biofilms. These results suggest that antibiotic exposure may have a direct impact on the pathophysiology of opportunistic trichosporonosis in patients at risk. Lay abstract This study showed that the vancomycin stimulated Trichosporon growth, induced morphological and physiological changes on their biofilms, and also enhanced their in vivo virulence. Although speculative, the stimulatory effect of vancomycin on fungal cells should be considered in a clinical scenario.


2016 ◽  
Vol 62 (1) ◽  
pp. 65-76
Author(s):  
Gordana Mirchevska ◽  
Maja Jurhar Pavlova ◽  
Elena Trajkovska-Dokic ◽  
Zaklina Cekovska ◽  
Gordana Jankoska ◽  
...  

Candida species are opportunistic yeasts that can be a serious threat for immunocompromised and critically ill patients, and a cause for increased morbidity and mortality in hospitalized patients. The aim of this study was to determine the frequency and distribution of different Candida species in clinical specimens in patients with increased risk for fungal infections, and to determine the antifungal susceptibility profile of invasive Candida species to antifungal agents. During a two year period, clinical specimens from 120 patients divided into 4 groups were analysed at the Institute of microbiology and parasitology, Faculty of Medicine, Skopje, Republic of Macedonia. Each of these 4 groups consisted of specimens from 30 patients, with primary immune deficiency, critically ill patients treated in the intensive care units (ICU), patients with mucosal candidiasis only, and patients with cystic fibrosis. All specimens were investigated with conventional mycological methods. Identification of Candida species was performed with VITEK-2 system (bioMérieux, France). E-test strips of fluconazole, voriconazole, amphotericin B and caspofungin (AB bioMerieux, France) were used for determination of the antifungal susceptibility profile. In this study, a total of 115 isolates of Candida species were confirmed in different clinical specimens (91 isolates from mucosal surfaces and 24 isolates from blood culture). Colonisation of mucosal membranes of gastrointestinal, respiratory and/or urinary tracts was registered in 56.67% (17/30), 56.67% (17/30), 90% (27/30) and 100% (30/30) of the specimens in the first, second, third and fourth group respectively. In all four groups of patients, the following Candida species were confirmed: C. albicans - 55%, C. glabrata - 17.6%, C. parapsilosis - 7.7%, C. tropicalis - 6.6%, unidentified Candida species - 4.4%, C. dubliniensis - 3.3%, C. kefyr - 2.2%, and one isolate of C. rugosa, C. pelliculosa and C. krusei each. Positive blood culture was registered in 23.33% specimens from the first group, 43.33% in the second group, 23.08% of the third group, and in one specimen of the fourth group. The most frequent isolates from blood culture were C. tropicalis and C. krusei, followed by C. albicans, C. parapsilosis and C. tropicalis, and in the second group C. albicans and C. pelliculosa were equally distributed, followed by C. parapsilosis and C. glabrata. All invasive isolates of Candida species were susceptible to amphotericin B, voriconazole and caspofungin. Resistance to fluconazole was registered in 8.3% (2/24) of all confirmed Candida species. Dose-dependent susceptibility to fluconazole was confirmed in 46% (11/24) of the isolates. Our study confirms high prevalence of colonisation and candidemia with non-albicans Candida species. Resistance to antifungal agents was registered only in two isolates of C. krusei. An epidemiological study is necessary for surveillance of dynamics of candidemia and antifungal susceptibility profile of invasive isolates of Candida species in our patients.


2020 ◽  
Vol 4 (5) ◽  
pp. 116-119
Author(s):  
Parul Uppal Malhotra ◽  
Neera Ohri ◽  
Yagyeshwar Malhotra ◽  
Anindita Mallik

Candida albicans is the most common Candida species isolated from the oral cavity both in healthy and diseased. Candida albicans is a dimorphic fungus existing both in blastopore phase (yeast phase) and the hyphal or mycelial phase. Although these organisms typically colonize mucocutaneous surfaces, the latter can be portals of entry into deeper tissues when host defences are compromised. Denture stomatitis is a common form of oral candidiasis that manifests as a diffuse inflammation of the maxillary denture bearing areas & is associated with angular cheilitis. At least 70% of individuals with clinical signs of denture stomatitis exhibit fungal growth & these conditions most likely result from yeast colonization of the oral mucosa combined with Bacterial colonization. Candida species act as an endogenous infecting agent on tissue predisposed by chronic trauma to microbial invasion. At one time, oral fungal infections were rare findings in general dentist's office. They were more commonly seen in hospitalized and severely debilitated patients. However with enhanced medical and pharmaceutical technology, increasing numbers of ambulatory immunosuppressed individuals with oral fungal infections are seeking out general dentists for diagnosis and treatment of these lesions.


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