scholarly journals Lactate Like Fluconazole Reduces Ergosterol Content in the Plasma Membrane and Synergistically Kills Candida albicans

2021 ◽  
Vol 22 (10) ◽  
pp. 5219
Author(s):  
Jakub Suchodolski ◽  
Jakub Muraszko ◽  
Przemysław Bernat ◽  
Anna Krasowska

Candida albicans is an opportunistic pathogen that induces vulvovaginal candidiasis (VVC), among other diseases. In the vaginal environment, the source of carbon for C. albicans can be either lactic acid or its dissociated form, lactate. It has been shown that lactate, similar to the popular antifungal drug fluconazole (FLC), reduces the expression of the ERG11 gene and hence the amount of ergosterol in the plasma membrane. The Cdr1 transporter that effluxes xenobiotics from C. albicans cells, including FLC, is delocalized from the plasma membrane to a vacuole under the influence of lactate. Despite the overexpression of the CDR1 gene and the increased activity of Cdr1p, C. albicans is fourfold more sensitive to FLC in the presence of lactate than when glucose is the source of carbon. We propose synergistic effects of lactate and FLC in that they block Cdr1 activity by delocalization due to changes in the ergosterol content of the plasma membrane.

2006 ◽  
Vol 5 (2) ◽  
pp. 321-329 ◽  
Author(s):  
Martine Bassilana ◽  
Robert A. Arkowitz

ABSTRACT We investigated the role of the highly conserved G protein Rac1 in the opportunistic pathogen Candida albicans. We identified and disrupted RAC1 and show here that, in contrast to CDC42, it is not necessary for viability or serum-induced hyphal growth but is essential for filamentous growth when cells are embedded in a matrix. Rac1 is localized to the plasma membrane, yet its distribution is more homogenous than that of Cdc42, with no enrichment at the tips of either buds or hyphae. In addition, fluorescence recovery after photobleaching results indicate that Rac1 and Cdc42 have different dynamics at the membrane. Furthermore, overexpression of Rac1 does not complement Cdc42 function, and conversely, overexpression of Cdc42 does not complement Rac1 function. Thus, Rac1 and Cdc42, although highly similar to one another, have different roles in C. albicans development.


2021 ◽  
Vol 7 (1) ◽  
pp. 57
Author(s):  
Hélène Authier ◽  
Marie Salon ◽  
Mouna Rahabi ◽  
Bénédicte Bertrand ◽  
Claude Blondeau ◽  
...  

Candida albicans is an opportunistic pathogen that causes mucosal gastrointestinal (GI) candidiasis tightly associated with gut inflammatory status. The emergence of drug resistance, the side effects of currently available antifungals and the high frequency of recurrent candidiasis indicate that new and improved therapeutics are needed. Probiotics have been suggested as a useful alternative for the management of candidiasis. We demonstrated that oral administration of Lactobacillus gasseri LA806 alone or combined with Lactobacillus helveticus LA401 in Candida albicans-infected mice decrease the Candida colonization of the oesophageal and GI tract, highlighting a protective role for these strains in C. albicans colonization. Interestingly, the probiotic combination significantly modulates the composition of gut microbiota towards a protective profile and consequently dampens inflammatory and oxidative status in the colon. Moreover, we showed that L. helveticus LA401 and/or L. gasseri LA806 orient macrophages towards a fungicidal phenotype characterized by a C-type lectin receptors signature composed of Dectin-1 and Mannose receptor. Our findings suggest that the use of the LA401 and LA806 combination might be a promising strategy to manage GI candidiasis and the inflammation it causes by inducing the intrinsic antifungal activities of macrophages. Thus, the probiotic combination is a good candidate for managing GI candidiasis by inducing fungicidal functions in macrophages while preserving the GI integrity by modulating the microbiota and inflammation.


2021 ◽  
Vol 1863 (1) ◽  
pp. 183486
Author(s):  
Francisco J. Ruiz-Castilla ◽  
Jan Bieber ◽  
Gabriel Caro ◽  
Carmen Michán ◽  
Hana Sychrova ◽  
...  

2015 ◽  
Vol 44 (1-2) ◽  
pp. 77-90 ◽  
Author(s):  
Barbara Chudzik ◽  
Mateusz Koselski ◽  
Aleksandra Czuryło ◽  
Kazimierz Trębacz ◽  
Mariusz Gagoś

Author(s):  
Andrea Boyd Tressler ◽  
Metabel Markwei ◽  
Chelsea Fortin ◽  
Meng Yao ◽  
Gary W. Procop ◽  
...  

2021 ◽  
Author(s):  
Rodrigo L Fabri ◽  
Jhamine C O Freitas ◽  
Ari S O Lemos ◽  
Lara M Campos ◽  
Irley O M Diniz ◽  
...  

Abstract Spilanthol is a bioactive alkylamide from the native Amazon plant species, Acmella oleracea. However, antifungal activities of spilanthol and its application to the therapeutic treatment of candidiasis remains to be explored. This study sought to evaluate the in vitro and in vivo antifungal activity of spilanthol previously isolated from A. oleracea (spilanthol(AcO)) against Candida albicans ATCC® 10231™, a multidrug-resistant fungal strain. Microdilution methods were used to determine inhibitory and fungicidal concentrations of spilanthol(AcO). In planktonic cultures, the fungal growth kinetics, yeast cell metabolic activity, cell membrane permeability and cell wall integrity were investigated. The effect of spilanthol(AcO) on the proliferation and adhesion of fungal biofilms was evaluated by whole slide imaging and scanning electron microscopy. The biochemical composition of the biofilm matrix was also analyzed. In parallel, spilanthol(AcO) was tested in vivo in an experimental vulvovaginal candidiasis model. Our in vitro analyses in C. albicans planktonic cultures detected a significant inhibitory effect of spilanthol(AcO), which affects both yeast cell membrane and cell wall integrity, interfering with the fungus growth. C. albicans biofilm proliferation and adhesion, as well as, carbohydrates and DNA in biofilm matrix were reduced after spilanthol(AcO) treatment. Moreover, infected rats treated with spilanthol(AcO) showed consistent reduction of both fungal burden and inflammatory processes compared to the untreated animals. Altogether, our findings demonstrated that spilanthol(AcO) is an bioactive compound against planktonic and biofilm forms of a multidrug resistant C. albicans strain. Furthermore, spilanthol(AcO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans. Lay Abstract This study sought to evaluate the antifungal activity of spilanthol against Candida albicans ATCC® 10 231™, a multidrug-resistant fungal strain. Our findings demonstrated that spilanthol(AcO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans.


Polymers ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 796 ◽  
Author(s):  
Le Yang ◽  
Zaijun Yang ◽  
Feng Zhang ◽  
Lijin Xie ◽  
Zhu Luo ◽  
...  

Long chain branched poly (lactic acid) (LCBPLA) was prepared via transesterification between high molecular weight poly (lactic acid) (PLA) and low molar mass monomer trimethylolpropane triacrylate (TMPTA) during melt blending in the presence of zinc oxide nanoparticles (nano-ZnO) as a transesterification accelerant in a torque rheometer. Compared with the traditional processing methods, this novel way is high-efficiency, environmentally friendly, and gel-free. The results revealed that chain restructuring reactions occurred and TMPTA was grafted onto the PLA backbone. The topological structures of LCBPLA were verified and investigated in detail. It was found that the concentration of the accelerants and the sampling occasion had very important roles in the occurrence of branching structures. When the nano-ZnO dosage was 0.4 phr and PLA was sampled at the time corresponding to the reaction peak in the torque curve, PLA exhibited a star-shaped topological structure with a high branching degree which could obviously affect the melt strength, extrusion foaming performances, and crystallization behaviors. Compared with pristine PLA, LCBPLA showed a higher melt strength, smaller cell diameter, and slower crystallization speed owing to the synergistic effects of nano-ZnO and the long chain branches introduced by the transesterification reaction in the system. However, severe degradation of the LCBPLAs would take place under a mixing time that was too long and lots of short linear chains generated due to the excessive transesterification reaction, with a sharp decline in melt strength.


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