Role of chromium reductases, antioxidants, and biosorption against oxidative damage of metals by Bacillus cereus.

Current research was performed to look for the performance of Bacillus cereus PY3 for metal detoxification. Strain PY3 was recognized as B. cereus using 16 S rRNA. Higher rate of removal of Zn and Cr (VI) by PY3 was obtained between pH 6-8 and 100-500 µg/mL in 24 h. Highest removal of Cr6+ by strain PY3 was achieved at acidic, neutral, and alkaline atmosphere, 100-300 µg Cr6+ /mL and 25-35°C. Supernatant of PY3 detoxified Cr6+ into Cr3+ then cell pellet (debris) adsorbed them. The mechanism of metal removal was due to the release of cytolic extracts. Release of antioxidants and bio-film played a protective role against cell damage. Metals increased antioxidants and bio-film formation. SEM images showed the smooth external structure of PY3 when cells were exposed to metals thus confirming the role of cells for detoxification. Results Above facts conclude that PY3 can remove metallic pollution in polluted soil.

Seaweed-Derived Phlorotannins: A Review of Multiple Biological Roles and Action Mechanisms.

Phlorotannins are a group of phenolic secondary metabolites isolated from a variety of brown algal species belonging to the Fucaceae, Sargassaceae, and Alariaceae families. The isolation of phlorotannins from various algal species has received a lot of interest owing to the fact that they have a range of biological features and are very biocompatible in their applications. Phlorotannins have a wide range of therapeutic biological actions, including antimicrobial, antidiabetic, antioxidant, anticancer, anti-inflammatory, anti-adipogenesis, and numerous other biomedical applications. The current review has extensively addressed the application of phlorotannins, which have been extensively investigated for the above-mentioned biological action and the underlying mechanism of action. Furthermore, the current review offers many ways to use phlorotannins to avoid certain downsides, such as low stability. This review article will assist the scientific community in investigating the greater biological significance of phlorotannins and developing innovative techniques for treating both infectious and non-infectious diseases in humans.

Mixed biofilms of pathogenic Candida-bacteria: regulation mechanisms and treatment strategies.

Mixed-species biofilm is one of the most frequently recorded clinical problems. Mixed biofilms develop as a result of interactions between microorganisms of a single or multiple species (e.g. bacteria and fungi). Candida spp., particularly Candida albicans, are known to associate with various bacterial species to form a multi-species biofilm. Mixed biofilms of Candida spp. have been previously detected in vivo and on the surfaces of many biomedical instruments. Treating infectious diseases caused by mixed biofilms of Candida and bacterial species has been challenging due to their increased resistance to antimicrobial drugs. Here, we review and discuss the clinical significance of mixed Candida-bacteria biofilms as well as the signalling mechanisms involved in Candida-bacteria interactions. We also describe possible approaches for combating infections associated with mixed biofilms, such as the use of natural or synthetic drugs and combination therapy. The review presented here is expected to contribute to the advances in the biomedical field on the understanding of underlying interaction mechanisms of pathogens in mixed biofilm, and alternative approaches to treating the related infections.

Black Seed Oil-Based Curcumin Nanoformulations Ameliorated Cuprizone-Induced Demyelination in the Mouse Hippocampus.

Multiple sclerosis (MS) is a neurodegenerative disease characterized by the demyelination of nerves, axonal damage, and neuroinflammation. Cognition impairment, pain, and loss of mobility are some of the usual complications of MS. It has been postulated that the overproduction of proinflammatory cytokines and reactive oxygen species (ROS) are the main factors that contribute to MS pathology. Among various animal models, the cuprizone model is the most widely used model for investigating MS-related pathology. We assessed the effects of cuprizone along with the protective effects of some black seed oil-based nanoformulations of curcumin with and without piperine, in mice hippocampus in terms of the changes in antioxidant enzymes, transcription factors, and cytokines during demyelination and remyelination processes. The results of behavioral studies point toward impairment in working memory following the feeding of cuprizone for 5 weeks. However, in treatment groups, mice seemed to prevent the toxic effects of cuprizone. Nanoformulations used in this study were found to be highly effective in lowering the amount of ROS as indicated by the levels of antioxidant enzymes like catalase, superoxide dismutase, glutathione, and glutathione peroxidase. Moreover, nanoformulations CCF and CCPF were observed resisting the toxic effects of cuprizone. We observed greater expression of NFκB-p65 in the CPZ group than in the control group. CCF nanoformulation had a better inhibitory effect on NFκB-p65 than other formulations. Histological examination of the hippocampus was also conducted. Nanoformulations used here were found effective in reversing MS-related pathophysiology and hence have the potential to be applied as adjuvant therapy for MS treatment.

Antibiofilm activity of certain phytocompounds and their synergy with fluconazole against Candida albicans biofilms.

OBJECTIVES: The aim of this study was to evaluate four phytocompounds (cinnamaldehyde, citral, eugenol and geraniol) for their in vitro inhibitory activity against pre-formed biofilms of Candida albicans alone or in combination with fluconazole and amphotericin B. These compounds were also tested at subinhibitory concentrations for their ability to inhibit biofilm formation. METHODS: The XTT reduction assay, light microscopy and scanning electron microscopy (SEM) were employed to determine the inhibitory effect of the test compounds on biofilms. A chequerboard method was used for combination studies. RESULTS: Both clinical and reference strains of C. albicans (C. albicans 04 and C. albicans SC5314, respectively) displayed formation of strong biofilms. Pre-formed Candida biofilms showed ≥1024× increased resistance to antifungal drugs and 2× increased resistance to cinnamaldehyde and geraniol, but no increased tolerance of eugenol. The test compounds were more active against pre-formed biofilms than amphotericin B and fluconazole. At 0.5× MIC, eugenol and cinnamaldehyde were the most inhibitory compounds against biofilm formation. Light and electron microscopic studies revealed the deformity of three-dimensional structures of biofilms formed in the presence of sub-MICs of eugenol and cinnamaldehyde. The cell membrane appeared to be the target site of compounds in both planktonic and sessile C. albicans cells, as observed by SEM. Combination studies showed that synergy was highest between eugenol and fluconazole (fractional inhibitory concentration index = 0.14) against pre-formed biofilms of C. albicans SC5314. CONCLUSIONS: Promising antibiofilm activity was displayed by eugenol and cinnamaldehyde, which also showed synergy with fluconazole in vitro. Further evaluation in in vivo systems is required to determine whether these findings can be exploited in treating biofilm-associated candidiasis.

Anti-candidal activity of essential oils alone and in combination with amphotericin B or fluconazole against multi-drug resistant isolates of Candida albicans.

Therapy for candidiasis is becoming problematic due to the toxicities of currently available antifungal agents and the increasing prevalence of resistance among the etiologic agents. Therefore, new antifungals and alternative approaches are needed. In this study, 20 fluconazole-resistant strains of Candida albicans were found to have varying levels of resistance to other azoles, i.e., itraconazole (MIC of 4-128 µg/ml) and ketoconazole (2-256 µg/ml). In addition, 13 of these isolates appeared resistant to amphotericin B (32-128 µg/ml). A total of 21 plant essential oils were screened for their antifungal activity against these multi-drug resistant isolates. The oils of Cymbopogon martini, i.e., citral and cinnamaldehyde, exhibited strong inhibitory activity with minimum inhibitory concentrations (MIC(50)) ranging from 90-100 µg/ml. The test oils were more effective than fluconazole and amphotericin B in inhibiting azole- and amphotericin B-resistant, as well as amphotericin B-susceptible isolates. The test oils and especially eugenol, exhibited significant synergy with fluconazole or amphotericin B against the test isolates. These findings suggest the possible effective use of certain oils alone or in combination with fluconazole or amphotericin B, against multi-drug resistant isolates of C. albicans.

Flaxseed oil ameliorates mercuric chloride-induced liver damage in rats.

BACKGROUND: Mercury is a relentless pollutant, and its toxicity contributes to significant health problems due to exposure to the environment. The present study has determined the impact of flaxseed oil on mercuric chloride (HgCl2)-mediated hepatic oxidative toxicity in rats. METHODS: Twenty-four healthy male Wistar rats were divided into four groups with six animals in each group. Group-A was the Control group treated with saline; Group-B received 1.0 ml oral dosage of flaxseed oil; Group-C was given 200 µl intraperitoneal injection of HgCl2, and Group-D received 1.0 ml oral dosage of flaxseed oil (one hour after treatment with 200 µl intraperitoneal injection of HgCl2. RESULTS: Mercuric chloride (HgCl2) increased the production of malondialdehyde (MDA), reactive oxygen species (ROS), glutathione (GSH), and the concentration of HgCl2 in the liver tissue with a simultaneous decrease in the activities of Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Furthermore, serum HgCl2 elevated the activity of alanine transaminase (ALT) and Lactate dehydrogenase (LDH). Histopathological changes showed that liver injury was caused by mercuric chloride. Treatment with flaxseed oil ameliorated ROS production and reversed enzymes in serum and liver. Also, a noticeable improvement was observed in all the histopathological characteristics in the rats. CONCLUSIONS: The findings of this study concluded that flaxseed oil had an outstanding remedial effect on mercuric chloride-mediated hepatic cytotoxicity.

Antifungal activity of essential oils and their synergy with fluconazole against drug-resistant strains of Aspergillus fumigatus and Trichophyton rubrum.

The aim of this study was to screen certain plant essential oils and active compounds for antifungal activity and their in vitro interaction with fluconazole against drug-resistant pathogenic fungi. The methods employed in this work included disc diffusion, broth macrodilution, time kill methods and checkerboard microtiter tests. Oil compositions were evaluated by gas chromatography-mass spectrometry (GC-MS) analysis. Transmission electron microscopy was used to assess the effect of essential oils on cellular structures of test fungi. Test fungal strains exhibited resistance to at least two drugs (fluconazole and itraconazole). Among the 21 essential oils or active compounds tested, ten showed promising antifungal activity. GC-MS analysis revealed the presence of major active compounds in the essential oils used. Cinnamaldehyde showed the most promising antifungal activity and killing potency against Aspergillus fumigatus MTCC2550 and Trichophyton rubrum IOA-9. Cinnamaldehyde showed strongest synergy with fluconazole against A. fumigatus and T. rubrum by reducing the minimum inhibitory concentration of fluconazole up to 8-fold. Zones of lysis of the cell wall and cell membrane appeared to be where cinnamaldehyde acted on fungi. This study highlights the broad spectrum antifungal activity of essential oils and active compounds and their synergy with fluconazole against drug-resistant fungi.

ROS-Mediated Necrosis by Glycolipid Biosurfactants on Lung, Breast, and Skin Melanoma Cells.

Cancer is one of the major leading causes of death worldwide. Designing the new anticancer drugs is remained a challenging task due to ensure complexicity of cancer etiology and continuosly emerging drug resistance. Glycolipid biosurfactants are known to possess various biological activities including antimicrobial, anticancer and antiviral properties. In the present study, we sought to decipher the mechanism of action of the glycolipids (lactonic-sophorolipd, acidic-sophorolipid, glucolipid, and bolalipid) against cancer cells using lung cancer cell line (A549), breast cancer cell line (MDA-MB 231), and mouse skin melanoma cell line (B16F10). Scratch assay and fluorescence microscopy revealed that glycolipids inhibit tumorous cell migration possibly by inhibiting actin filaments. Fluorescence activated cell sorter (FACS) analysis exhibited that lactonic sophorolipid and glucolipid both induced the reactive oxygen species, altered the mitochondrial membrane potential (ΔΨ) and finally led to the cell death by necrosis. Furthermore, combinatorial effect of lactonic-sophorolipd and glucolipid demonstrated synergistic interaction on A549 cell line whereas additive effect on MDA-MB 231 and B16F10 cell lines. Our study has highlighted that lactonic-sophorolipd and glucolipid could be useful for developing new anticancer drugs either alone or in combination.

Brain Metabolite, N-Acetylaspartate Is a Potent Protein Aggregation Inhibitor.

Deposition of toxic protein inclusions is a common hallmark of many neurodegenerative disorders including Alzheimer's disease, Parkinson disease etc. N-acetylaspartate (NAA) is an important brain metabolite whose levels got altered under various neurodegenerative conditions. Indeed, NAA has been a widely accepted biological marker for various neurological disorders. We have also reported that NAA is a protein stabilizer. In the present communication, we investigated the role of NAA in modulating the aggregation propensity on two model proteins (carbonic anhydrase and catalase). We discovered that NAA suppresses protein aggregation and could solubilize preformed aggregates.

Preparation and In Vitro-In Vivo Evaluation of Luteolin Loaded Gastroretentive Microsponge for the Eradication of Helicobacter pylori Infections.

The current study aimed to develop a luteolin gastric floating microsponge for targeting Helicobacter pylori. The microsponge formulations were prepared by a quasi-emulsion method, and then evaluated for various physicochemical variables. The best microsponge was further assessed for drug-polymer interactions, surface morphology, in vivo floating, and in vitro anti H. pylori activity. The formulation which exhibited comparatively good production yield (64.45% ± 0.83), high entrapment efficiency (67.33% ± 3.79), prolonged in vitro floating time (>8 h), and sustained in-vitro drug release was selected as the best microsponge. The SEM study revealed that the best microsponge was spherical in shape and has a porous surface with interconnecting channels. DSC and XRD studies demonstrated the dispersion of luteolin in the polymeric matrix of the microsponge. Ultrasonography confirmed that the best microsponge could in the rat stomach for 4 h. The in vitro MIC results indicate that the anti H. pylori activity of the best microsponge was almost doubled and more sustained compared to pure luteolin. To conclude, it can be said that the developed luteolin gastric floating microsponge could be a better option to effectively eradicate H. pylori infections and the histopathological and pharmacodynamic assessments of our best microsponge can be expected to provide a rewarding outcome.

Screening of certain medicinal plants from India for their anti-quorum sensing activity.

Discovery of quorum sensing (QS) system to coordinate virulence and biofilm formation in bacterial pathogens has triggered search for safe, stable and non-toxic anti-QS compounds from natural products. Ethanolic extracts of 24 Indian medicinal plants were tested by agar well and disc diffusion assay for anti-QS activity using Chromobacterium violaceum (CV12472 and CVO26) reporter strains. AHL from C. violaceum CV31532 was isolated and partially purified for its use in CVO26 based bioassay. Effect on swarming-motility of Pseudomonas aeruginosa (PAO1) was also recorded at sub-MIC concentrations of extracts. Of the 24 medicinal plants screened Hemidesmus indicus (L.) Schult (root), Holarrhena antidysenterica (Roth) A.DC. (bark), Mangifera indica L. (seed) Punica granatum L. (pericarp) and Psoralea corylifolia L. (seed) demonstrated varying level of inhibition of violacein production in the reporter strains. Moreover, a significant reduction in swarms was recorded over control. The inhibition of violacein production and swarming motility may be due to direct or indirect interference on QS by active constituents or the interactive effect of different phytocompounds present in the extracts. These plant extracts may be selected for activity guided fractionation to identify and characterize the active principle.

Modulation of quorum sensing controlled behaviour of bacteria by growing seedling, seed and seedling extracts of leguminous plants.

Effect of growing seedling, seeds and seedlings extracts from seven leguminous plants (Pisum sativum, Vigna radiata, Vigna mungo, Cajanus cajan, Lentil culinaris, Cicer arietinum and Trigonella foenum graecum) were screened for their ability to influence quorum sensing controlled pigment production in Chromobacterium violaceum indicator strains (CV12472 and CVO26). Germinating seedling and seedling extracts of only P. sativum (pea) showed inhibition of violacein production. Interestingly, the T. foenum graecum (fenugreek) seed extracts enhances the pigment production. Quorum sensing regulated swarming motility in Pseudomonas aerugionsa PAO1 was reduced by pea seedling extract while enhanced by the fenugreek seed extracts. These findings suggest that plant metabolites of some legumes interact actively with bacterial quorum sensing and could modulate its associated functions.

Synergistic interaction of eugenol and antimicrobial drugs in eradication of single and mixed biofilms of Candida albicans and Streptococcus mutans.

In vitro eradication of the C. albicans and S. mutans mixed biofilms by eugenol alone and in combination with the antimicrobial drugs. Previously characterized strains of C. albicans (CAJ-01 and CAJ-12) and S. mutans MTCC497 were used to evaluate the eradication of biofilms using XTT reduction assay, viability assay, time dependent killing assay and scanning electron microscopy (SEM). Synergistic interaction was assessed by checkerboard method. Sessile MIC (SMIC) of eugenol was equivalent to the planktonic MIC (PMIC) against C. albicans and S. mutans mixed biofilms. SMIC of fluconazole and azithromycin was increased upto 1000-folds over PMIC. Eradication of single or mixed biofilms was evident from the viability assay and SEM. At 1 × MIC of eugenol, log10CFU count of C. albicans cells were decreased from 6.3 to 4.2 and 3.8 (p < 0.05) in single and mixed biofilms, respectively. SEM studies revealed the eradication of C. albicans and S. mutans cells from glass surface at 800 µg/mL concentration of eugenol. Time dependent killing assay showed dose dependent effect of eugenol on pre-formed CAJ-01, CAJ-12 and S. mutans biofilm cells. Eugenol was highly synergistic with fluconazole (FICI = 0.156) against CAJ-12 single biofilms. However, the combination of eugenol and azithromycin showed maximum synergy (FICI = 0.140) against pre-formed C. albicans and S. mutans mixed biofilms. These findings highlighted the promising efficacy of eugenol in the eradication of biofilms of two oral pathogens (C. albicans and S. mutans) in vitro and could also be exploited in synergy with fluconazole and azithromycin in controlling oral infections.

Expedition into Taurine Biology: Structural Insights and Therapeutic Perspective of Taurine in Neurodegenerative Diseases.

Neurodegenerative diseases (NDs) are characterized by the accumulation of misfolded proteins. The hallmarks of protein aggregation in NDs proceed with impairment in the mitochondrial function, besides causing an enhancement in endoplasmic reticulum (ER) stress, neuroinflammation and synaptic loss. As accumulation of misfolded proteins hampers normal neuronal functions, it triggers ER stress, which leads to the activation of downstream effectors formulating events along the signaling cascade-referred to as unfolded protein response (UPRER) -thereby controlling cellular gene expression. The absence of disease-modifying therapeutic targets in different NDs, and the exponential increase in the number of cases, makes it critical to explore new approaches to treating these devastating diseases. In one such approach, osmolytes (low molecular weight substances), such as taurine have been found to promote protein folding under stress conditions, thereby averting aggregation of the misfolded proteins. Maintaining the structural integrity of the protein, taurine-mediated resumption of protein folding prompts a shift in folding homeostasis more towards functionality than towards aggregation and degradation. Together, taurine enacts protection in NDs by causing misfolded proteins to refold, so as to regain their stability and functionality. The present study provides recent and useful insights into understanding the progression of NDs, besides summarizing the genetics of NDs in correlation with mitochondrial dysfunction, ER stress, neuroinflammation and synaptic loss. It also highlights the structural and functional aspects of taurine in imparting protection against the aggregation/misfolding of proteins, thereby shifting the focus more towards the development of effective therapeutic modules that could avert the development of NDs.

In vitro efficacy of eugenol in inhibiting single and mixed-biofilms of drug-resistant strains of Candida albicans and Streptococcus mutans.

BACKGROUND: Candida albicans is frequently associated with mixed infections of Streptococcus mutans in plaque biofilms. These pathogens under chemical interactions resulting in mixed biofilm development have turned it into a prevalent and costly oral disease, which is not successfully being treated by existing chemotherapeutics. HYPOTHESIS: Considering the need for newer drugs to overcome this challenge, the present study was aimed to investigate the efficacy of eugenol in inhibiting single and mixed biofilms of C. albicans and S. mutans. METHODS: The broth dilution assay was used to determine drug resistance in the test strains. Biofilm formation on polystyrene microtiter plate was studied by XTT reduction assay whereas biofilm development on glass coverslips was assessed using 0.1% crystal violet and visualised under light microscope. Single and mixed biofilms formed on glass coverslips in the presence and absence of eugenol was analysed by scanning electron microscopy. RESULTS: In our study, all the thirteen strains of C. albicans were resistant to fluconazole, itraconazole, ketoconazole, amphotericin B except C. albicans (CAJ-01) and C. albicans MTCC3017 which were sensitive to fluconazole. S. mutans MTCC497 was resistant to ampicillin, azithromycin, ceftriaxone and vancomycin. Among all the strains of C. albicans, CAJ-01, C. albicans ATCC90028 and C. albicans MTCC3017 formed strong biofilms and rest of the strains considered as moderate to weak biofilm formers. S. mutans MTCC497 was also formed strong biofilms. Eugenol showed concentration dependent anti-biofilm activity against single and mixed biofilms of C. albicans (CAJ-01) and S. mutans MTCC497. At sub-MIC of eugenol (100 µg/ml), the biofilm formation was 36.37% and 29.72% in CAJ-01 and S. mutans MTCC497, respectively, whereas 52.65% in mixed biofilms. The cell viability assay showed significant reduction (p < 0.05) in the log10 CFU/ml from 6.3 to 4.8 at 200 µg/ml of eugenol for CAJ-01, whereas, from 6.4 to 3.8 and 5.3 for S. mutans MTCC497 strains in single and mixed biofilms, respectively. Scanning electron microscopy showed the disruption of cell membrane and matrix structure in both single and mixed biofilms. CONCLUSIONS: Eugenol at sub-MICs effectively inhibited single and mixed biofilms formed by the drug resistant strains of two oral pathogens, C. albicans and S. mutans through multiple mode of action.

Translational Shift of HSP90 as a Novel Therapeutic Target from Cancer to Neurodegenerative Disorders: An Emerging Trend in the Cure of Alzheimer's and Parkinson's Diseases.

BACKGROUND: Despite having extensive research, the apparent pathogenic mechanism of Alzheimer's disease (AD), Parkinson's disease (PD) and other neurodegenerative diseases (NDs) have not yet fully understood. The Heat Shock Protein 90 (HSP90), a ubiquitous molecular chaperone, found to have an important role in averting protein misfolding and aggregation through inhibition of apoptotic activity in neuro-inflammatory diseases. Various researchers have confirmed its role in maintaining aberrant neuronal protein's functional stability to a great capacity. It is also involved in regulating the activity of the heat shock factor-1 (HSF-1), a vital regulator of the heat shock response mechanism that cells employ to protect themselves against stress conditions. This quality makes the HSP90 an ideal candidate for novel inhibitory target for therapeutic modality in NDs. METHODS: An extensive literature search was conducted for relevant studies on PubMed, ScienceDirect, Springer- Link etc. The articles were carefully read in their entirety to determine whether they contained information on the topic of interest. Additionally, the reference sections of these articles were searched manually to get more relevant and eligible studies. RESULTS: We have taken an attempt to reveal how HSP90 play important roles with key neuronal proteins involved in supporting the AD and PD pathology. We have further on structure-function relationship of HSP90 to understand its efficacy as a new target in AD and PD by utilizing new generation of HSP90 inhibitors such as geldanamycin and its derivatives, 17-AAG, 17-DMAG, IPI-504, radicicol and its derivatives. HSP90 inhibition leads to suppress atypical neuronal activity by assisting in improving protein aggregation and its related toxicity. Further, the formation of neuronal aggregates is also influenced by HSP90 inhibitors and provides protection from toxicity of protein through HSF-1 activation and HSP70 induction in AD. CONCLUSION: HSP90 inhibition has emerged as a potential target in treating diverse array of diseases especially NDs. In spite of a large amount of research in this direction, the clear cut molecular mechanisms of HSPs associated with neuroprotection are still poorly elucidated and hence more focus is needed toward HSPs and its inhibitory mechanism. The development of HSP90 inhibitors that induce heat-shock response without cytotoxicity for treatment of NDs are still in its early stage. A panel of novel designed research and clinical trial studies are greatly needed to establish the therapeutic reliability and efficacy of HSPs in order to provide best cure for NDs.

Carum copticum and Thymus vulgaris oils inhibit virulence in Trichophyton rubrum and Aspergillus spp.

Emergence of drug-resistant strains has demanded for alternative means of combating fungal infections. Oils of Carum copticum and Thymus vulgaris have long been used in ethnomedicine for ailments of various fungal infections. Since their activity has not been reported in particular against drug-resistant fungi, this study was aimed to evaluate the effects of oils of C. copticum and T. vulgaris on the growth and virulence of drug-resistant strains of Aspergillus spp. and Trichophyton rubrum. The gas chromatography-mass spectrometry analysis revealed thymol constituting 44.71% and 22.82% of T. vulgaris and C. copticum, respectively. Inhibition of mycelial growth by essential oils was recorded in the order of thymol > T. vulgaris > C. copticum against the tested strains. RBC lysis assay showed no tested oils to be toxic even up to concentration two folds higher than their respective MFCs. Thymol exhibited highest synergy in combination with fluconazole against Aspergillus fumigatus MTCC2550 (FICI value 0.187) and T. rubrum IOA9 (0.156) as determined by checkerboard method. Thymol and T. vulgaris essential oil were equally effective against both the macro and arthroconidia growth (MIC 72 µg/mL). A > 80% reduction in elastase activity was recorded for A. fumigatus MTCC2550 by C. copticum, T. vulgaris oils and thymol. The effectiveness of these oils against arthroconidia and synergistic interaction of thymol and T. vulgaris with fluconazole can be exploited to potentiate the antifungal effects of fluconazole against drug-resistant strains of T. rubrum and Aspergillus spp.

Phenyl aldehyde and propanoids exert multiple sites of action towards cell membrane and cell wall targeting ergosterol in Candida albicans.

In the present study, two phyto-compounds phenyl aldehyde (cinnamaldehyde) and propanoid (eugenol) were selected to explore their modes of action against Candida albicans. Electron microscopy, flow cytometry and spectroscopic assays were employed to determine the targets of these compounds. Treatment of C. albicans (CA04) with sub-MICs of cinnamaldehyde (50 µg/mL) and eugenol (200 µg/mL) indicated multiple sites of action including damages to cell walls, cell membranes, cytoplasmic contents and other membranous structures as observed under electron microscopy. Concentration and time dependent increase in the release of cytoplasmic contents accompanied with change in extracellular K+ concentration was recorded. Exposure of Candida cells at 4 × MIC of cinnaamldehyde and eugenol resulted in 40.21% and 50.90% dead cells, respectively as revealed by flow cytometry analysis. Treatment of Candida cells by cinnamaldehyde and eugenol at 0.5 × MIC showed 67.41% and 76.23% reduction in ergosterol biosynthesis, respectively. The binding assays reflected the ability of compounds to bind with the ergosterol. Our findings have suggested that the membrane damaging effects of phenyl aldehyde and propanoids class of compounds is attributed to their ability to inhibit ergosterol biosynthesis and simultaneously binding with ergosterol. Indirect or secondary action of these compounds on cell wall is also expected as revealed by electron microscopic studies.