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  1. Article ; Online: Mechanistic Insights into the Anticandidal Action of Vanillin Reveal Disruption of Cell Surface Integrity and Mitochondrial Functioning.

    Saibabu, Venkata / Fatima, Zeeshan / Khan, Luqman Ahmad / Hameed, Saif

    Infectious disorders drug targets

    2020  Volume 21, Issue 3, Page(s) 405–415

    Abstract: Background: Considering the emergence of multidrug resistance (MDR) in prevalent human fungal pathogen, Candida albicans, there is a parallel spurt in the development of novel strategies aimed to disrupt MDR. Compounds from natural resources could be ... ...

    Abstract Background: Considering the emergence of multidrug resistance (MDR) in prevalent human fungal pathogen, Candida albicans, there is a parallel spurt in the development of novel strategies aimed to disrupt MDR. Compounds from natural resources could be exploited as efficient antifungal drugs owing to their structural diversity, cost effectiveness and negligible side effects.
    Objective: The present study elucidates the antifungal mechanisms of Vanillin (Van), a natural food flavoring agent against Candida albicans.
    Methods: Antifungal activities were assessed by broth microdilution and spot assays. Membrane and cell wall perturbations were studied by PI uptake, electron microscopy, plasma membrane H+ extrusion activity and estimation of ergosterol and chitin contents. Mitochondrial functioning was studied by growth on non-fermentable carbon sources, rhodamine B labeling and using retrograde signaling mutants. Gene expressions were validated by semi-quantitative RT-PCR.
    Results: We observed that the antifungal activity of Van was not only limited to clinical isolates of C. albicans but also against non-albicans species of Candida. Mechanistic insights revealed the effect of Van on cell surface integrity as evident from hypersensitivity against membrane perturbing agent SDS, depleted ergosterol levels, transmission electron micrographs and diminished plasma membrane H+ extrusion activity. In addition, spot assays with cell wall perturbing agents, scanning electron micrographs, delayed sedimentation rate and lower chitin content further substantiate cell wall damage by Van. Furthermore, Van treated cells underwent mitochondrial dysfunctioning via impaired retrograde signaling leading to abrogated iron homeostasis and DNA damage. All the perturbed phenotypes were also validated by RT-PCR depicting differential regulation of genes (NPC2, KRE62, FTR2 and CSM3) in response to Van.
    Conclusion: Together, our results suggested that Van is promising antifungal agent that may be advocated for further investigation in therapeutic strategies to treat Candida infections.
    MeSH term(s) Antifungal Agents/pharmacology ; Benzaldehydes ; Candida albicans ; Cell Membrane ; Humans
    Chemical Substances Antifungal Agents ; Benzaldehydes ; vanillin (CHI530446X)
    Language English
    Publishing date 2020-07-02
    Publishing country United Arab Emirates
    Document type Journal Article
    ZDB-ID 2234298-9
    ISSN 2212-3989 ; 1871-5265
    ISSN (online) 2212-3989
    ISSN 1871-5265
    DOI 10.2174/1871526520666200702134110
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Efficiency of vanillin in impeding metabolic adaptability and virulence of Candida albicans by inhibiting glyoxylate cycle, morphogenesis, and biofilm formation

    Venkata Saibabu / Zeeshan Fatima / Kamal Ahmad / Luqman Khan / Saif Hameed

    Current Medical Mycology, Vol 6, Iss 1, Pp 1-

    2020  Volume 8

    Abstract: Background and Purpose: Candida albicans is the fourth most common cause of nosocomial fungal infections across the world. The current drug regimens are suffering from such drawbacks as drug resistance, toxicity, and costliness; accordingly, they ... ...

    Abstract Background and Purpose: Candida albicans is the fourth most common cause of nosocomial fungal infections across the world. The current drug regimens are suffering from such drawbacks as drug resistance, toxicity, and costliness; accordingly, they highlight the need for the discovery of novel drug agents. The metabolic adaptability under low-carbon conditions and expression of functional virulence traits mark the success of pathogens to cause infection. The metabolic pathways, such as glyoxylate cycle (GC), enable C. albicans to survive under glucose-deficient conditions prevalent in the hostile niche. Therefore, the key enzymes, namely isocitrate lyase (ICL) and malate synthase (MLS), represent attractive agents against C. albicans. Similarly, virulence traits, such as morphogenesis and biofilm formation, are the crucial determinants of C. albicans pathogenicity. Regarding this, the present study was conducted to uncover the role of vanillin (Van), a natural food flavoring agent, in inhibiting GC, yeast-to-hyphal transition, and biofilm formation in human fungal pathogen C. albicans. Materials and Methods: For the determination of hypersensitivity under low-glucose conditions, phenotypic susceptibility assay was utilized. In addition, enzyme activities were estimated based on crude extracts while in-silico binding was confirmed by molecular docking. The assessment of morphogenesis was accomplished using hyphalinducing media, and biofilm formation was estimated using calcofluor staining, MTT assay, and biomass measurement. Additionally, the in vivo efficacy of Van was demonstrated using Caenorhabditis elegans nematode model. Results: Based on the results, Van was found to be a potent GC inhibitor that phenocopied ICL1 deletion mutant and displayed hypersensitivity under low-carbon conditions. Accordingly, Van facilitated the inhibition of ICL and MLS activities in vitro. Molecular docking analyses revealed the in-silico binding affinity of Van with Icl1p and Mls1p. Those analyses were also confirmative of the ...
    Keywords biofilm ; caenorhabditis elegans ; candida ; glyoxylate cycle ; morphogenesis ; vanillin ; Internal medicine ; RC31-1245 ; Biology (General) ; QH301-705.5
    Subject code 616
    Language English
    Publishing date 2020-03-01T00:00:00Z
    Publisher Mazandaran University of Medical Sciences
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article: Efficiency of vanillin in impeding metabolic adaptability and virulence of

    Venkata, Saibabu / Zeeshan, Fatima / Kamal, Ahmad / Luqman, Ahmad Khan / Saif, Hameed

    Current medical mycology

    2020  Volume 6, Issue 1, Page(s) 1–8

    Abstract: Background and purpose: Candida albicans: Materials and methods: For the determination of hypersensitivity under low-glucose conditions, phenotypic susceptibility assay was utilized. In addition, enzyme activities were estimated based on crude ... ...

    Abstract Background and purpose: Candida albicans
    Materials and methods: For the determination of hypersensitivity under low-glucose conditions, phenotypic susceptibility assay was utilized. In addition, enzyme activities were estimated based on crude extracts while in-silico binding was confirmed by molecular docking. The assessment of morphogenesis was accomplished using hyphal-inducing media, and biofilm formation was estimated using calcofluor staining, MTT assay, and biomass measurement. Additionally, the in vivo efficacy of Van was demonstrated using
    Results: Based on the results, Van was found to be a potent GC inhibitor that phenocopied
    Conclusion: As the findings of the present study indicated, Van is a persuasive natural compound that warrants further attention to exploit its anticandidal potential.
    Language English
    Publishing date 2020-05-11
    Publishing country Iran
    Document type Journal Article
    ZDB-ID 3015705-5
    ISSN 2423-3420 ; 2423-3439
    ISSN (online) 2423-3420
    ISSN 2423-3439
    DOI 10.18502/cmm.6.1.2501
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Octyl gallate triggers dysfunctional mitochondria leading to ROS driven membrane damage and metabolic inflexibility along with attenuated virulence in Candida albicans.

    Saibabu, Venkata / Fatima, Zeeshan / Ahmad, Kamal / Khan, Luqman Ahmad / Hameed, Saif

    Medical mycology

    2019  Volume 58, Issue 3, Page(s) 380–392

    Abstract: Recently the high incidence of worldwide Candida infections has substantially increased. The growing problem about toxicity of antifungal drugs and multidrug resistance aggravates the need for the development of new effective strategies. Natural ... ...

    Abstract Recently the high incidence of worldwide Candida infections has substantially increased. The growing problem about toxicity of antifungal drugs and multidrug resistance aggravates the need for the development of new effective strategies. Natural compounds in this context represent promising alternatives having potential to be exploited for improving human health. The present study was therefore designed to evaluate the antifungal effect of a naturally occurring phenolic, octyl gallate (OG), on Candida albicans and to investigate the underlying mechanisms involved. We demonstrated that OG at 25 μg/ml could effectively inhibit C. albicans. Mechanistic insights revealed that OG affects mitochondrial functioning as Candida cells exposed to OG did not grow on non-fermentable carbon sources. Dysfunctional mitochondria triggered generation of reactive oxygen species (ROS), which led to membrane damage mediated by lipid peroxidation. We explored that OG inhibited glucose-induced reduction in external pH and causes decrement in ergosterol levels by 45%. Furthermore, OG impedes the metabolic flexibility of C. albicans by inhibiting the glyoxylate enzyme isocitrate lyase, which was also confirmed by docking analysis. Additionally, OG affected virulence traits such as morphological transition and cell adherence. Furthermore, we depicted that OG not only prevented biofilm formation but eliminates the preformed biofilms. In vivo studies with Caenorhabditis elegans nematode model confirmed that OG could enhance the survival of C. elegans after infection with Candida. Toxicity assay using red blood cells showed only 27.5% haemolytic activity. Taken together, OG is a potent inhibitor of C. albicans that warrants further structural optimization and pharmacological investigations.
    MeSH term(s) Animals ; Biological Products/pharmacology ; Caenorhabditis elegans ; Candida albicans/drug effects ; Candida albicans/pathogenicity ; Cell Membrane/drug effects ; Cell Membrane/pathology ; Gallic Acid/analogs & derivatives ; Gallic Acid/pharmacology ; Isocitrate Lyase/antagonists & inhibitors ; Mitochondria/drug effects ; Mitochondria/pathology ; Molecular Docking Simulation ; Reactive Oxygen Species/metabolism ; Virulence/drug effects
    Chemical Substances Biological Products ; Reactive Oxygen Species ; octyl gallate (079IIA2811) ; Gallic Acid (632XD903SP) ; Isocitrate Lyase (EC 4.1.3.1)
    Language English
    Publishing date 2019-06-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 1421796-x
    ISSN 1460-2709 ; 1369-3786
    ISSN (online) 1460-2709
    ISSN 1369-3786
    DOI 10.1093/mmy/myz054
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Nonphotodynamic Roles of Methylene Blue: Display of Distinct Antimycobacterial and Anticandidal Mode of Actions.

    Pal, Rahul / Ansari, Moiz A / Saibabu, Venkata / Das, Shrayanee / Fatima, Zeeshan / Hameed, Saif

    Journal of pathogens

    2018  Volume 2018, Page(s) 3759704

    Abstract: Significance of methylene blue (MB) in photodynamic therapy against microbes is well established. Previously, we have reported the antifungal potential of MB ... ...

    Abstract Significance of methylene blue (MB) in photodynamic therapy against microbes is well established. Previously, we have reported the antifungal potential of MB against
    Language English
    Publishing date 2018-01-31
    Publishing country Egypt
    Document type Journal Article
    ZDB-ID 2662334-1
    ISSN 2090-3065 ; 2090-3057
    ISSN (online) 2090-3065
    ISSN 2090-3057
    DOI 10.1155/2018/3759704
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Insights into the intracellular mechanisms of citronellal in Candida albicans: implications for reactive oxygen species-mediated necrosis, mitochondrial dysfunction, and DNA damage.

    Saibabu, Venkata / Singh, Shweta / Ansari, Moiz A / Fatima, Zeeshan / Hameed, Saif

    Revista da Sociedade Brasileira de Medicina Tropical

    2017  Volume 50, Issue 4, Page(s) 524–529

    Abstract: Introduction: Citronellal (Cit) possesses antifungal activity and has possible implications for reactive oxygen species (ROS) generation in Candida albicans. In this study, the effects of Cit on ROS generation and the mechanisms by which Cit exerts anti- ...

    Abstract Introduction: Citronellal (Cit) possesses antifungal activity and has possible implications for reactive oxygen species (ROS) generation in Candida albicans. In this study, the effects of Cit on ROS generation and the mechanisms by which Cit exerts anti-Candida effects were examined.
    Methods: A 2',7'-dichlorodihydrofluorescein diacetate assay was used to assess oxidative damage. Cell necrosis was determined by flow cytometry after FITC-Annexin V staining. Mitochondrial function was studied based on mitochondrial potential, metabolic activity (MTT assay), and phenotypic susceptibility on a non-fermentable carbon source. Membrane intactness and DNA damage were estimated by a propidium iodide (PI) uptake assay and 4',6-diamidino-2-phenylindole (DAPI) staining.
    Results: ROS generation was enhanced in response to Cit, leading to necrosis (2%). Additional hallmarks of cell death in response to Cit, such as mitochondrial membrane depolarization and DNA damage, were also observed. Cit treatment resulted in dysfunctional mitochondria, as evidenced by poor labeling with the mitochondrial membrane potential-sensitive probe rhodamine B, reduced metabolic activity (61.5%), and inhibited growth on a non-fermentable carbon source. Furthermore, Cit induced DNA damage based on DAPI staining. These phenotypes were reinforced by RT-PCR showing differences in gene expression (30-60%) between control and Cit-treated cells. Finally, PI uptake in the presence of sodium azide confirmed non-intact membranes and suggested that Cit activity is independent of the energy status of the cell.
    Conclusions: Cit possesses dual anticandidal mechanisms, including membrane-disruptive and oxidative damage. Taken together, our data demonstrated that cit could be used as a prominent antifungal drug.
    Language English
    Publishing date 2017-07
    Publishing country Brazil
    Document type Journal Article
    ZDB-ID 1038126-0
    ISSN 1678-9849 ; 0037-8682
    ISSN (online) 1678-9849
    ISSN 0037-8682
    DOI 10.1590/0037-8682-0114-2017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Therapeutic Potential of Dietary Phenolic Acids.

    Saibabu, Venkata / Fatima, Zeeshan / Khan, Luqman Ahmad / Hameed, Saif

    Advances in pharmacological sciences

    2015  Volume 2015, Page(s) 823539

    Abstract: Although modern lifestyle has eased the quality of human life, this lifestyle's related patterns have imparted negative effects on health to acquire multiple diseases. Many synthetic drugs are invented during the last millennium but most if not all of ... ...

    Abstract Although modern lifestyle has eased the quality of human life, this lifestyle's related patterns have imparted negative effects on health to acquire multiple diseases. Many synthetic drugs are invented during the last millennium but most if not all of them possess several side effects and proved to be costly. Convincing evidences have established the premise that the phytotherapeutic potential of natural compounds and need of search for novel drugs from natural sources are of high priority. Phenolic acids (PAs) are a class of secondary metabolites spread throughout the plant kingdom and generally involved in plethora of cellular processes involved in plant growth and reproduction and also produced as defense mechanism to sustain various environmental stresses. Extensive research on PAs strongly suggests that consumption of these compounds hold promise to offer protection against various ailments in humans. This paper focuses on the naturally derived PAs and summarizes the action mechanisms of these compounds during disease conditions. Based on the available information in the literature, it is suggested that use of PAs as drugs is very promising; however more research and clinical trials are necessary before these bioactive molecules can be made for treatment. Finally this review provides greater awareness of the promise that natural PAs hold for use in the disease prevention and therapy.
    Language English
    Publishing date 2015-09-09
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2397786-3
    ISSN 1687-6342 ; 1687-6334
    ISSN (online) 1687-6342
    ISSN 1687-6334
    DOI 10.1155/2015/823539
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Nonphotodynamic Roles of Methylene Blue: Display of Distinct Antimycobacterial and Anticandidal Mode of Actions

    Pal, Rahul / Ansari, Moiz A / Saibabu, Venkata / Das, Shrayanee / Fatima, Zeeshan / Hameed, Saif

    Journal of pathogens. 2018 Jan. 31, v. 2018

    2018  

    Abstract: Significance of methylene blue (MB) in photodynamic therapy against microbes is well established. Previously, we have reported the antifungal potential of MB against Candida albicans. The present study attempts to identify additional antimicrobial effect ...

    Abstract Significance of methylene blue (MB) in photodynamic therapy against microbes is well established. Previously, we have reported the antifungal potential of MB against Candida albicans. The present study attempts to identify additional antimicrobial effect of MB against another prevalent human pathogen, Mycobacterium tuberculosis (MTB). We explored that MB is efficiently inhibiting the growth of Mycobacterium at 15.62 μg/ml albeit in bacteriostatic manner similar to its fungistatic nature. We uncovered additional cell surface phenotypes (colony morphology and cell sedimentation rate) which were impaired only in Mycobacterium. Mechanistic insights revealed that MB causes energy dependent membrane perturbation in both C. albicans and Mycobacterium. We also confirmed that MB leads to enhanced reactive oxygen species generation in both organisms that could be reversed upon antioxidant supplementation; however, DNA damage could only be observed in Mycobacterium. We provided evidence that although biofilm formation was disrupted in both organisms, cell adherence to human epithelial cells was inhibited only in Mycobacterium. Lastly, RT-PCR results showed good correlation with the biochemical assay. Together, apart from the well-established role of MB in photodynamic therapy, this study provides insights into the distinct antimicrobial mode of actions in two significant human pathogens, Candida and Mycobacterium, which can be extrapolated to improve our understanding of finding novel therapeutic options.
    Keywords Candida albicans ; DNA damage ; Mycobacterium tuberculosis ; animal pathogens ; antibacterial properties ; antifungal properties ; biofilm ; energy ; epithelial cells ; humans ; mechanism of action ; methylene blue ; microorganisms ; phenotype ; photochemotherapy ; reactive oxygen species ; reverse transcriptase polymerase chain reaction ; sedimentation rate
    Language English
    Dates of publication 2018-0131
    Publishing place Hindawi
    Document type Article
    ZDB-ID 2662334-1
    ISSN 2090-3065 ; 2090-3057
    ISSN (online) 2090-3065
    ISSN 2090-3057
    DOI 10.1155/2018/3759704
    Database NAL-Catalogue (AGRICOLA)

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  9. Article ; Online: Therapeutic Potential of Dietary Phenolic Acids

    Venkata Saibabu / Zeeshan Fatima / Luqman Ahmad Khan / Saif Hameed

    Advances in Pharmacological Sciences, Vol

    2015  Volume 2015

    Abstract: Although modern lifestyle has eased the quality of human life, this lifestyle’s related patterns have imparted negative effects on health to acquire multiple diseases. Many synthetic drugs are invented during the last millennium but most if not all of ... ...

    Abstract Although modern lifestyle has eased the quality of human life, this lifestyle’s related patterns have imparted negative effects on health to acquire multiple diseases. Many synthetic drugs are invented during the last millennium but most if not all of them possess several side effects and proved to be costly. Convincing evidences have established the premise that the phytotherapeutic potential of natural compounds and need of search for novel drugs from natural sources are of high priority. Phenolic acids (PAs) are a class of secondary metabolites spread throughout the plant kingdom and generally involved in plethora of cellular processes involved in plant growth and reproduction and also produced as defense mechanism to sustain various environmental stresses. Extensive research on PAs strongly suggests that consumption of these compounds hold promise to offer protection against various ailments in humans. This paper focuses on the naturally derived PAs and summarizes the action mechanisms of these compounds during disease conditions. Based on the available information in the literature, it is suggested that use of PAs as drugs is very promising; however more research and clinical trials are necessary before these bioactive molecules can be made for treatment. Finally this review provides greater awareness of the promise that natural PAs hold for use in the disease prevention and therapy.
    Keywords Medicine (General) ; R5-920
    Subject code 571
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Hindawi Publishing Corporation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Insights into the intracellular mechanisms of citronellal in Candida albicans

    Venkata Saibabu / Shweta Singh / Moiz A. Ansari / Zeeshan Fatima / Saif Hameed

    Revista da Sociedade Brasileira de Medicina Tropical, Vol 50, Iss 4, Pp 524-529

    implications for reactive oxygen species-mediated necrosis, mitochondrial dysfunction, and DNA damage

    Abstract: Abstract INTRODUCTION Citronellal (Cit) possesses antifungal activity and has possible implications for reactive oxygen species (ROS) generation in Candida albicans. In this study, the effects of Cit on ROS generation and the mechanisms by which Cit ... ...

    Abstract Abstract INTRODUCTION Citronellal (Cit) possesses antifungal activity and has possible implications for reactive oxygen species (ROS) generation in Candida albicans. In this study, the effects of Cit on ROS generation and the mechanisms by which Cit exerts anti-Candida effects were examined. METHODS A 2′,7′-dichlorodihydrofluorescein diacetate assay was used to assess oxidative damage. Cell necrosis was determined by flow cytometry after FITC-Annexin V staining. Mitochondrial function was studied based on mitochondrial potential, metabolic activity (MTT assay), and phenotypic susceptibility on a non-fermentable carbon source. Membrane intactness and DNA damage were estimated by a propidium iodide (PI) uptake assay and 4',6-diamidino-2-phenylindole (DAPI) staining. RESULTS ROS generation was enhanced in response to Cit, leading to necrosis (2%). Additional hallmarks of cell death in response to Cit, such as mitochondrial membrane depolarization and DNA damage, were also observed. Cit treatment resulted in dysfunctional mitochondria, as evidenced by poor labeling with the mitochondrial membrane potential-sensitive probe rhodamine B, reduced metabolic activity (61.5%), and inhibited growth on a non-fermentable carbon source. Furthermore, Cit induced DNA damage based on DAPI staining. These phenotypes were reinforced by RT-PCR showing differences in gene expression (30-60%) between control and Cit-treated cells. Finally, PI uptake in the presence of sodium azide confirmed non-intact membranes and suggested that Cit activity is independent of the energy status of the cell. CONCLUSIONS Cit possesses dual anticandidal mechanisms, including membrane-disruptive and oxidative damage. Taken together, our data demonstrated that cit could be used as a prominent antifungal drug.
    Keywords Reactive oxygen species ; Necrosis ; Mitochondria ; DNA ; Propidium iodide ; Candida albicans ; Arctic medicine. Tropical medicine ; RC955-962
    Subject code 610
    Language English
    Publisher Sociedade Brasileira de Medicina Tropical (SBMT)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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