The role of Candida albicans stress response pathways in antifungal tolerance and resistance

Iyer, Kali R.; Robbins, Nicole; Cowen, Leah E.

doi:10.1016/j.isci.2022.103953

Cited by 48 publications

(27 citation statements)

References 85 publications

(142 reference statements)

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“…The synthesized zinc oxide nanoparticle shows effective antifungal activity against C. albicans, the most important fungal pathogen that is a threat to human health . This observation is in line with the earlier reported works on zinc oxide nanoparticles and C.…”

Section: Resultssupporting

confidence: 91%

Biogenic Synthesis of Zinc Oxide Nanoparticles Mediated by the Extract of Terminalia catappa Fruit Pericarp and Its Multifaceted Applications

Fernandes,

Jesudoss M,

Nizam

et al. 2023

ACS Omega

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Zinc oxide nanoparticles (ZnO-NPs) were biosynthesized by using the pericarp aqueous extract from Terminalia catappa Linn. These NPs were characterized using various analytical techniques such as X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, ultraviolet (UV) spectroscopy, dynamic light scattering (DLS), and scanning electron microscopy (SEM), and XRD studies of the nanoparticles reported mean size as 12.58 nm nanocrystals with highest purity. Further SEM analysis emphasized the nanoparticles to be spherical in shape. The functional groups responsible for capping and stabilizing the NPs were identified with FTIR studies. DLS studies of the synthesized NPs reported ζ potential as −10.1 mV and exhibited stable colloidal solution. These characterized ZnO-NPs were evaluated for various biological applications such as antibacterial, antifungal, antioxidant, genotoxic, biocompatibility, and larvicidal studies. To explore its multidimensional application in the field of medicine. NPs reported a potential antimicrobial activity at a concentration of 200 μg/mL against bacterial strains in the decreasing order of Streptococcus pyogenes > Streptococcus aureus > Streptococcus typhi > Streptococcus aeruginosa and against the fungi Candida albicans. In vitro studies of RBC hemolysis with varying concentrations of NPs confirm their biocompatibility with IC 50 value of 211.4 μg/mL. The synthesized NPs' DPPH free radical scavenging activity was examined to extend their antioxidant applications. The antiproliferation and genetic toxicity were studied with meristematic cells of Allium cepa reported with mitotic index (MI index) of 1.2% at the concentration of 1000 μg/mL. NPs exhibited excellent Larvicidal activity against Culex quinquefasciatus larvae with the highest mortality rate as 98% at 4 mg/L. Our findings elicit the therapeutic potentials of the synthesized zinc oxide NPs.

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Section: Resultssupporting

confidence: 91%

Biogenic Synthesis of Zinc Oxide Nanoparticles Mediated by the Extract of Terminalia catappa Fruit Pericarp and Its Multifaceted Applications

Fernandes,

Jesudoss M,

Nizam

et al. 2023

ACS Omega

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“…Candida albicans is an opportunistic pathogenic yeast commonly associated with superficial and systemic infections [ 1 ]. C. albicans has become difficult to kill due to its virulence factors and increasing antifungal resistance [ 2 , 3 ]. The virulence factors include yeast-to-hyphae transition and biofilm formation [ 2 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Antifungal Properties of Biogenic Selenium Nanoparticles Functionalized with Nystatin for the Inhibition of Candida albicans Biofilm Formation

et al. 2023

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In the present study, biogenic selenium nanoparticles (SeNPs) have been prepared using Paenibacillus terreus and functionalized with nystatin (SeNP@PVP_Nystatin nanoconjugates) for inhibiting growth, morphogenesis, and a biofilm in Candida albicans. Ultraviolet–visible spectroscopy analysis has shown a characteristic absorption at 289, 303, and 318 nm, and X-ray diffraction analysis has shown characteristic peaks at different 2θ values for SeNPs. Electron microscopy analysis has shown that biogenic SeNPs are spherical in shape with a size in the range of 220–240 nm. Fourier transform infrared spectroscopy has confirmed the functionalization of nystatin on SeNPs (formation of SeNP@PVP_Nystatin nanoconjugates), and the zeta potential has confirmed the negative charge on the nanoconjugates. Biogenic SeNPs are inactive; however, nanoconjugates have shown antifungal activities on C. albicans (inhibited growth, morphogenesis, and a biofilm). The molecular mechanism for the action of nanoconjugates via a real-time polymerase chain reaction has shown that genes involved in the RAS/cAMP/PKA signaling pathway play an important role in antifungal activity. In cytotoxic studies, nanoconjugates have inhibited only 12% growth of the human embryonic kidney cell line 293 cells, indicating that the nanocomposites are not cytotoxic. Thus, the biogenic SeNPs produced by P. terreus can be used as innovative and effective drug carriers to increase the antifungal activity of nystatin.

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“…Calcineurin, a calcium-calmodulin-activated phosphatase consisting of a heterodimer with the catalytic and regulatory subunits Cna1 and Cnb1 16 controls the expression of several genes by dephosphorylating the transcriptional regulator Crz1 through binding to calmodulin, a calcium sensor 17 , 18 . It is essential for the growth of Cryptococcus neoformans , a pathogenic basidiomycete yeast like T. asahii , at 37 °C, as well as its virulence in a rabbit model of cryptococcal meningitis and cation homeostasis 19 , 20 .…”

Section: Introductionmentioning

confidence: 99%

A critical role of calcineurin in stress responses, hyphal formation, and virulence of the pathogenic fungus Trichosporon asahii

Matsumoto

Yoshikawa

Nagamachi

et al. 2022

Sci Rep

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Trichosporon asahii is a conditional pathogenic fungus that causes severe and sometimes fatal infections in immunocompromised patients. While calcineurin, an essential component of a calcium-dependent signaling pathway, is known to regulate stress resistance and virulence of some pathogenic fungi, its role in T. asahii has not been investigated. Here, we demonstrated that calcineurin gene-deficient T. asahii mutants are sensitive to high temperature as well as cell-membrane and cell-wall stress, and exhibit decreased hyphal formation and virulence against silkworms. Growth of T. asahii mutants deficient in genes encoding subunits of calcineurin, cna1 and cnb1, was delayed at 40 °C. The cna1 and cnb1 gene-deficient mutants also showed sensitivity to sodium dodecyl sulfate, Congo red, dithiothreitol, and tunicamycin. On the other hand, these mutants exhibited no sensitivity to caffeine, sorbitol, monensin, CaCl2, LiCl, NaCl, amphotericin B, fluconazole, or voriconazole. The ratio of hyphal formation in the cna1 and cnb1 gene-deficient mutants was decreased. Moreover, the virulence of the cna1 and cnb1 gene-deficient mutants against silkworms was attenuated. These phenotypes were restored by re-introducing each respective gene into the gene-deficient mutants. Our findings suggest that calcineurin has a role in regulating the cellular stress response and virulence of T. asahii.

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The role of Candida albicans stress response pathways in antifungal tolerance and resistance

Cited by 48 publications

References 85 publications

Biogenic Synthesis of Zinc Oxide Nanoparticles Mediated by the Extract of Terminalia catappa Fruit Pericarp and Its Multifaceted Applications

Biogenic Synthesis of Zinc Oxide Nanoparticles Mediated by the Extract of Terminalia catappa Fruit Pericarp and Its Multifaceted Applications

Antifungal Properties of Biogenic Selenium Nanoparticles Functionalized with Nystatin for the Inhibition of Candida albicans Biofilm Formation

A critical role of calcineurin in stress responses, hyphal formation, and virulence of the pathogenic fungus Trichosporon asahii

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