scholarly journals Selective Antifungal Activity and Fungal Biofilm Inhibition of Tryptophan Center Symmetrical Short Peptide

2021 ◽  
Vol 22 (15) ◽  
pp. 8231
Author(s):  
Shuli Chou ◽  
Qiuke Li ◽  
Hua Wu ◽  
Jinze Li ◽  
Yung-Fu Chang ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Antifungal Agents ◽  
Fungal Cell ◽  
Biofilm Inhibition ◽  
Resistance Selection ◽  
Medicinal Treatment ◽  
Receptor Recognition ◽  
Membrane Physiology ◽  
High Binding Affinity ◽  
Lipoteichoic Acids

Candida albicans, an opportunistic fungus, causes dental caries and contributes to mucosal bacterial dysbiosis leading to a second infection. Furthermore, C. albicans forms biofilms that are resistant to medicinal treatment. To make matters worse, antifungal resistance has spread (albeit slowly) in this species. Thus, it has been imperative to develop novel, antifungal drug compounds. Herein, a peptide was engineered with the sequence of RRFSFWFSFRR-NH2; this was named P19. This novel peptide has been observed to exert disruptive effects on fungal cell membrane physiology. Our results showed that P19 displayed high binding affinity to lipopolysaccharides (LPS), lipoteichoic acids (LTA) and the plasma membrane phosphatidylinositol (PI), phosphatidylserine (PS), cardiolipin, and phosphatidylglycerol (PG), further indicating that the molecular mechanism of P19 was not associated with the receptor recognition, but rather related to competitive interaction with the plasma membrane. In addition, compared with fluconazole and amphotericin B, P19 has been shown to have a lower potential for resistance selection than established antifungal agents.

Recent Status and Advancements in the Development of Antifungal Agents: Highlights on Plant and Marine Based Antifungals

2019 ◽  
Vol 19 (10) ◽  
pp. 812-830 ◽  
Author(s):  
P. Marie Arockianathan ◽  
Monika Mishra ◽  
Rituraj Niranjan
Keyword(s):  
Cell Wall ◽  
Antifungal Agents ◽  
Fungal Diseases ◽  
Fungal Cell Wall ◽  
Fungal Resistance ◽  
Ergosterol Biosynthesis ◽  
Fungal Cell ◽  
Ergosterol Synthesis ◽  
Glucan Synthesis ◽  
Anti Fungal

The developing resistance in fungi has become a key challenge, which is being faced nowadays with the available antifungal agents in the market. Further search for novel compounds from different sources has been explored to meet this problem. The current review describes and highlights recent advancement in the antifungal drug aspects from plant and marine based sources. The current available antifungal agents act on specific targets on the fungal cell wall, like ergosterol synthesis, chitin biosynthesis, sphingolipid synthesis, glucan synthesis etc. We discuss some of the important anti-fungal agents like azole, polyene and allylamine classes that inhibit the ergosterol biosynthesis. Echinocandins inhibit β-1, 3 glucan synthesis in the fungal cell wall. The antifungals poloxins and nikkomycins inhibit fungal cell wall component chitin. Apart from these classes of drugs, several combinatorial therapies have been carried out to treat diseases due to fungal resistance. Recently, many antifungal agents derived from plant and marine sources showed potent activity. The renewed interest in plant and marine derived compounds for the fungal diseases created a new way to treat these resistant strains which are evident from the numerous literature publications in the recent years. Moreover, the compounds derived from both plant and marine sources showed promising results against fungal diseases. Altogether, this review article discusses the current antifungal agents and highlights the plant and marine based compounds as a potential promising antifungal agents.

scholarly journals Sublethal Injury and Resuscitation of Candida albicans after Amphotericin B Treatment

2003 ◽  
Vol 47 (4) ◽  
pp. 1200-1206 ◽  
Author(s):  
Robert S. Liao ◽  
Robert P. Rennie ◽  
James A. Talbot
Keyword(s):  
Cell Death ◽  
Candida Albicans ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Sybr Green ◽  
Sequential Treatment ◽  
Tetrazolium Salt ◽  
Fungal Cell ◽  
Sublethal Injury

ABSTRACT Amphotericin B treatment was previously shown to inhibit Candida albicans reproduction and reduce the fluorescence of vitality-specific dyes without causing a corresponding increase in the fluorescence of the mortality-specific dyes bis-(1,3-dibutylbarbituric acid)trimethine oxonol and SYBR Green Ι. In the present study, we have confirmed these results and have shown that the numbers of CFU are reduced by 99.9% by treatment with 0.5 μg of amphotericin B per ml for 10 h at 35°C. This reduction was not due to fungal cell death. First, the level of reduction of the tetrazolium salt 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide increased in the presence of concentrations of amphotericin B that caused greater than 90% reductions in the numbers of CFU. Second, fungal cells treated with amphotericin B at a concentration of 0.5 μg/ml were resuscitated by further incubation at 22°C for 15 h in the continued presence of amphotericin B. Third, recovery of the ability to replicate was prevented by sequential treatment with 20 μg of miconazole per ml, which also increased the fluorescence of mortality-specific dyes to near the maximal levels achieved with 0.9 μg of amphotericin B per ml. Sequential treatment with fluconazole and flucytosine did not increase the levels of staining with the mortality-specific dyes. Itraconazole was less effective than ketoconazole, which was less effective than miconazole. The practice of equating the loss of the capacity of C. albicans to form colonies with fungal cell death may give incorrect results in assays with amphotericin B, and the results of assays with caution with other antifungal agents that are lipophilic or that possess significant postantifungal effects may need to be interpreted.

scholarly journals Plant-Derived Substances in the Fight Against Infections Caused by Candida Species

2020 ◽  
Vol 21 (17) ◽  
pp. 6131
Author(s):  
Ibeth Guevara-Lora ◽  
Grazyna Bras ◽  
Justyna Karkowska-Kuleta ◽  
Miriam González-González ◽  
Kinga Ceballos ◽  
...  
Keyword(s):  
Candida Species ◽  
Biofilm Formation ◽  
Defense Mechanisms ◽  
Antifungal Agents ◽  
Standard Treatment ◽  
Antifungal Drugs ◽  
Host Immune System ◽  
Plant Metabolites ◽  
Fungal Cell ◽  
Mucosal Surfaces

Yeast-like fungi from the Candida genus are predominantly harmless commensals that colonize human skin and mucosal surfaces, but under conditions of impaired host immune system change into dangerous pathogens. The pathogenicity of these fungi is typically accompanied by increased adhesion and formation of complex biofilms, making candidal infections challenging to treat. Although a variety of antifungal drugs have been developed that preferably attack the fungal cell wall and plasma membrane, these pathogens have acquired novel defense mechanisms that make them resistant to standard treatment. This causes an increase in the incidence of candidiasis and enforces the urgent need for an intensified search for new specifics that could be helpful, alone or synergistically with traditional drugs, for controlling Candida pathogenicity. Currently, numerous reports have indicated the effectiveness of plant metabolites as potent antifungal agents. These substances have been shown to inhibit growth and to alter the virulence of different Candida species in both the planktonic and hyphal form and during the biofilm formation. This review focuses on the most recent findings that provide evidence of decreasing candidal pathogenicity by different substances of plant origin, with a special emphasis on the mechanisms of their action. This is a particularly important issue in the light of the currently increasing frequency of emerging Candida strains and species resistant to standard antifungal treatment.

scholarly journals What Makes Oral Candidiasis Recurrent Infection? A Clinical View

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Azmi M. G. Darwazeh ◽  
Tamer A. Darwazeh
Keyword(s):  
Health Care ◽  
Oral Health ◽  
Oral Cavity ◽  
Antifungal Agents ◽  
Oral Candidiasis ◽  
Recurrent Infection ◽  
Predisposing Factor ◽  
Fungal Cell ◽  
Incorrect Diagnosis ◽  
The Common

Clinical oral Candida infection (candidiasis) is one of the common oral mucosal infections, and its management is usually frustrating due to either treatment failure or recurrence. Historically, oral candidiasis has been branded as disease of diseased. The unsuccessful management of oral candidiasis can due to either incorrect diagnosis, failure to identify (or correct) the underlying predisposing factor(s), or inaccurate prescription of antifungal agents. Failure to properly treat oral candidiasis will lead to persistence of the fungal cell in the oral cavity and hence recurrence of infection. The oral health care provider should be aware of these fall pits in order to successfully manage oral candidiasis.

scholarly journals Up against the Wall: Is Yeast Cell Wall Integrity Ensured by Mechanosensing in Plasma Membrane Microdomains?

2014 ◽  
Vol 81 (3) ◽  
pp. 806-811 ◽  
Author(s):  
Christian Kock ◽  
Yves F. Dufrêne ◽  
Jürgen J. Heinisch
Keyword(s):  
Cell Wall ◽  
Plasma Membrane ◽  
Yeast Cell ◽  
Antifungal Drugs ◽  
Cell Wall Integrity ◽  
Yeast Cell Wall ◽  
Membrane Microdomains ◽  
Wall Structure ◽  
Fungal Cell ◽  
Membrane Spanning

ABSTRACTYeast cell wall integrity (CWI) signaling serves as a model of the regulation of fungal cell wall synthesis and provides the basis for the development of antifungal drugs. A set of five membrane-spanning sensors (Wsc1 to Wsc3, Mid2, and Mtl1) detect cell surface stress and commence the signaling pathway upon perturbations of either the cell wall structure or the plasma membrane. We here summarize the latest advances in the structure/function relationship primarily of the Wsc1 sensor and critically review the evidence that it acts as a mechanosensor. The relevance and physiological significance of the information obtained for the function of the other CWI sensors, as well as expected future developments, are discussed.

scholarly journals Interaction of Cryptococcus neoformans Extracellular Vesicles with the Cell Wall

2014 ◽  
Vol 13 (12) ◽  
pp. 1484-1493 ◽  
Author(s):  
Julie M. Wolf ◽  
Javier Espadas-Moreno ◽  
Jose L. Luque-Garcia ◽  
Arturo Casadevall
Keyword(s):  
Cell Wall ◽  
Plasma Membrane ◽  
Cryptococcus Neoformans ◽  
Extracellular Vesicles ◽  
Protein Composition ◽  
Multivesicular Body ◽  
Dense Matrix ◽  
Fungal Cell ◽  
Content Type ◽  
Pass Through

ABSTRACTCryptococcus neoformansproduces extracellular vesicles containing a variety of cargo, including virulence factors. To become extracellular, these vesicles not only must be released from the plasma membrane but also must pass through the dense matrix of the cell wall. The greatest unknown in the area of fungal vesicles is the mechanism by which these vesicles are released to the extracellular space given the presence of the fungal cell wall. Here we used electron microscopy techniques to image the interactions of vesicles with the cell wall. Our goal was to define the ultrastructural morphology of the process to gain insights into the mechanisms involved. We describe single and multiple vesicle-leaving events, which we hypothesized were due to plasma membrane and multivesicular body vesicle origins, respectively. We further utilized melanized cells to “trap” vesicles and visualize those passing through the cell wall. Vesicle size differed depending on whether vesicles left the cytoplasm in single versus multiple release events. Furthermore, we analyzed different vesicle populations for vesicle dimensions and protein composition. Proteomic analysis tripled the number of proteins known to be associated with vesicles. Despite separation of vesicles into batches differing in size, we did not identify major differences in protein composition. In summary, our results indicate that vesicles are generated by more than one mechanism, that vesicles exit the cell by traversing the cell wall, and that vesicle populations exist as a continuum with regard to size and protein composition.

scholarly journals Econazole inhibits thapsigargin-induced platelet calcium influx by mechanisms other than cytochrome P-450 inhibition

1993 ◽  
Vol 295 (2) ◽  
pp. 525-529 ◽  
Author(s):  
J G Vostal ◽  
J C Fratantoni
Keyword(s):  
Plasma Membrane ◽  
Antifungal Agents ◽  
Calcium Influx ◽  
Calcium Stores ◽  
Alternative Mechanism ◽  
Resting Cells ◽  
Calcium Efflux ◽  
Plasma Membrane Permeability ◽  
Cytochrome P 450 ◽  
Internal Calcium

Cytochrome P-450 has been suggested as a mediator of the signal between depleted platelet calcium stores and an increase in plasma membrane permeability to calcium which follows depletion of the stores. This hypothesis is based on the observations that inhibitors of cytochrome P-450, such as the imidazole antifungal agents, also inhibit influx of a calcium surrogate (manganese) into calcium-depleted platelets. We tested the effects of econazole and of a cytochrome P-450 inhibitor, carbon monoxide (CO), on thapsigargin (TG)-induced platelet 45Ca2+ influx. TG specifically depletes internal calcium stores and activates store-regulated calcium influx. Econazole blocked 45Ca2+ influx when it was added before TG (IC50 11 microM). Econazole at a concentration (20 microM) that inhibited 83% of TG-induced calcium influx was not inhibitory to TG-induced calcium efflux from 45Ca(2+)-loaded platelets, and did not affect calcium fluxes in resting platelets. This econazole concentration was also inhibitory to calcium influx even when it was added after the stores had been calcium-depleted by EGTA and TG for 15 min and the signal to increase calcium influx had already been generated. Inhibition of cytochrome P-450 with CO bubbled through platelet suspensions did not change calcium influx in resting cells and potentiated TG-induced calcium influx (160% of control calcium accumulation at 20 min). This effect appeared to be concentration-dependent, such that a 5 min exposure to CO produced a greater influx potentiation than a 3 min exposure. These observations indicate that (1) cytochrome P-450 does not mediate store-regulated calcium influx, and (2) econazole probably inhibits store-regulated calcium influx by an alternative mechanism, such as interaction with plasma membrane calcium channels.

scholarly journals Fluconazole and Lipopeptide Surfactin Interplay During Candida albicans Plasma Membrane and Cell Wall Remodeling Increases Fungal Immune System Exposure

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 314 ◽  
Author(s):  
Jakub Suchodolski ◽  
Daria Derkacz ◽  
Jakub Muraszko ◽  
Jarosław J. Panek ◽  
Aneta Jezierska ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Plasma Membrane ◽  
Immune System ◽  
Antifungal Drugs ◽  
Stable Complex ◽  
Host Immune System ◽  
Chitin Synthesis ◽  
Fungal Cell ◽  
In Silico Studies

Recognizing the β-glucan component of the Candida albicans cell wall is a necessary step involved in host immune system recognition. Compounds that result in exposed β-glucan recognizable to the immune system could be valuable antifungal drugs. Antifungal development is especially important because fungi are becoming increasingly drug resistant. This study demonstrates that lipopeptide, surfactin, unmasks β-glucan when the C. albicans cells lack ergosterol. This observation also holds when ergosterol is depleted by fluconazole. Surfactin does not enhance the effects of local chitin accumulation in the presence of fluconazole. Expression of the CHS3 gene, encoding a gene product resulting in 80% of cellular chitin, is downregulated. C. albicans exposure to fluconazole changes the composition and structure of the fungal plasma membrane. At the same time, the fungal cell wall is altered and remodeled in a way that makes the fungi susceptible to surfactin. In silico studies show that surfactin can form a complex with β-glucan. Surfactin forms a less stable complex with chitin, which in combination with lowering chitin synthesis, could be a second anti-fungal mechanism of action of this lipopeptide.

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