Influence of subinhibitory antifungal concentrations on extracellular hydrolases and biofilm production by Candida albicans recovered from Egyptian patients

El-Houssaini, Houdaii H.; Elnabawy, Omnia M.; Nasser, Hebatallah A.; Elkhatib, Walid F.

doi:10.1186/s12879-019-3685-0

Cited by 14 publications

(16 citation statements)

References 45 publications

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“…Many different antifungal drugs affect key virulence attributes of fungal pathogens when present at subinhibitory concentrations. For example, in Candida extracellular hydrolase production (43), phospholipase production (44), hemolytic activity (45), and biofilm formation (43,46) are inhibited by various antifungal drugs, including AMB, NYS, FLC, and caspofungin. The capacity of Candida to make biofilms is a key virulence factor, as these protect the organism from the immune system and antifungal drug treatment, allowing it to persist inside the host (47).…”

Section: Discussionmentioning

confidence: 99%

Lactoferrin Is Broadly Active against Yeasts and Highly Synergistic with Amphotericin B

Fernandes

Weeks

Carter

2020

Antimicrob Agents Chemother

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Lactoferrin (LF) is a multifunctional milk protein with antimicrobial activity against a range of pathogens. While numerous studies report that LF is active against fungi, there are considerable differences in the level of antifungal activity and the capacity of LF to interact with other drugs. Here we undertook a comprehensive evaluation of the antifungal spectrum of activity of three defined sources of LF across 22 yeast and 24 mold species and assessed its interactions with six widely used antifungal drugs. LF was broadly and consistently active against all yeast species tested (MICs, 8 to 64 μg/ml), with the extent of activity being strongly affected by iron saturation. LF was synergistic with amphotericin B (AMB) against 19 out of 22 yeast species tested, and synergy was unaffected by iron saturation but was affected by the extent of LF digestion. LF-AMB combination therapy significantly prolonged the survival of Galleria mellonella wax moth larvae infected with Candida albicans or Cryptococcus neoformans and decreased the fungal burden 12- to 25-fold. Evidence that LF directly interacts with the fungal cell surface was seen via scanning electron microscopy, which showed pore formation, hyphal thinning, and major cell collapse in response to LF-AMB synergy. Important virulence mechanisms were disrupted by LF-AMB treatment, which significantly prevented biofilms in C. albicans and C. glabrata, inhibited hyphal development in C. albicans, and reduced cell and capsule size and phenotypic diversity in Cryptococcus. Our results demonstrate the potential of LF-AMB as an antifungal treatment that is broadly synergistic against important yeast pathogens, with the synergy being attributed to the presence of one or more LF peptides.

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Section: Discussionmentioning

confidence: 99%

Lactoferrin Is Broadly Active against Yeasts and Highly Synergistic with Amphotericin B

Fernandes

Weeks

Carter

2020

Antimicrob Agents Chemother

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“…Mechanisms of resistance to polyene antifungals often occur due to overexpression and mutation in ERG1, ERG2, ERG3, ERG4, ERG6, ERG11 and ERG11 genes, which are involved in ergosterol biosynthesis. This leads to the accumulation of sterols other than ergosterol, resulting in dramatic disruption of cell membrane permeability [ 11 , 12 , 13 ]. For decades, polyenes were thought to provoke their toxic effects by intercalating into membranes containing ergosterol and forming channels that cross through the membrane, cause leakage of cellular components, and ultimately lead to cell death.…”

Section: Introductionmentioning

confidence: 99%

Docking Prediction, Antifungal Activity, Anti-Biofilm Effects on Candida spp., and Toxicity against Human Cells of Cinnamaldehyde

et al. 2020

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Objective: This study evaluated the antifungal activity of cinnamaldehyde on Candida spp. In vitro and in situ assays were carried out to test cinnamaldehyde for its anti-Candida effects, antibiofilm activity, effects on fungal micromorphology, antioxidant activity, and toxicity on keratinocytes and human erythrocytes. Statistical analysis was performed considering α = 5%. Results: The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of cinnamaldehyde ranged from 18.91 μM to 37.83 μM. MIC values did not change in the presence of 0.8 M sorbitol, whereas an 8-fold increase was observed in the presence of ergosterol, suggesting that cinnamaldehyde may act on the cell membrane, which was subsequently confirmed by docking analysis. The action of cinnamaldehyde likely includes binding to enzymes involved in the formation of the cytoplasmic membrane in yeast cells. Cinnamaldehyde-treated microcultures showed impaired cellular development, with an expression of rare pseudo-hyphae and absence of chlamydoconidia. Cinnamaldehyde reduced biofilm adherence by 64.52% to 33.75% (p < 0.0001) at low concentrations (378.3–151.3 µM). Cinnamaldehyde did not show antioxidant properties. Conclusions: Cinnamaldehyde showed fungicidal activity through a mechanism of action likely related to ergosterol complexation; it was non-cytotoxic to keratinocytes and human erythrocytes and showed no antioxidant activity.

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“…Fluconazole, in turn, needed concentrations greater than 4 × MIC to obtain activity similar to A1Cl. El‐Houssaini et al (2019) showed that fluconazole has no antibiofilm effect at subinhibitory concentrations. Our results on ex vivo models were promising as it mimics human nail infections as much as possible.…”

Section: Discussionmentioning

confidence: 99%

Antifungal activity of 2-chloro-N-phenylacetamide, docking and molecular dynamics studies against clinical isolates of Candida tropicalis and Candida parapsilosis

Silva

Pereira

Cordeiro

et al. 2022

Journal of Applied Microbiology

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Aims This study evaluated the antifungal, antibiofilm and molecular docking of 2‐chloro‐N‐phenylacetamide against clinical isolates of Candida tropicalis and Candida parapsilosis. Methods and results Minimum inhibitory concentration (MIC) of the test drugs was determined by microdilution. A1Cl obtained MIC values ranging from 16 and 256 μg/ml. Fluconazole MIC ranging from 16 and 512 μg/ml. MIC of A1Cl showed fungicide activity, emphasizing the solid antifungal potential of this drug. An association study was performed with A1Cl and fluconazole (checkerboard), revealing indifference by decreasing. Thus, we conducted this study using A1Cl isolated. In the micromorphological assay, the test drugs reduced the production of virulence structures compared to the control (concentration‐dependent effect). A1Cl inhibited in vitro biofilm formation at all concentrations tested (1/4MIC to 8 × MIC) (p < 0.05) and reduced mature biofilm biomass (p < 0.05) against C. tropicalis and C. parapsilosis. In the ex vivo biofilm susceptibility testing (human nails fragments), A1Cl inhibited biofilm formation and reduced mature biofilm biomass (p < 0.05) more than 50% at MIC. Fluconazole had a similar effect at 4 × MIC. In silico studies suggest that the mechanism of antifungal activity of A1Cl involves the inhibition of the enzyme dihydrofolate reductase (DHFR) rather than geranylgeranyltransferase‐I. Conclusions The results suggest that A1Cl is a promising antifungal agent. Furthermore, this activity is related to attenuation of expression of virulence factors and antibiofilm effects against C. tropicalis and C. parapsilosis. Significance and impact of the study Our study provides the first evidence that A1Cl, a novel synthetic drug, has fungicidal effects against C. tropicalis and C. parapsilosis. Furthermore, in vitro and ex vivo biofilms assays have demonstrated the potential antibiofilm of A1Cl. The mechanism of action involves inhibiting the enzyme DHFR, which was supported by in silico analyses. Therefore, this potential can be explored as a therapeutic alternative for onychomycosis and, at the same time, contribute to decreasing the resistance of clinical isolates of C. tropicalis and C. parapsilosis.

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Influence of subinhibitory antifungal concentrations on extracellular hydrolases and biofilm production by Candida albicans recovered from Egyptian patients

Cited by 14 publications

References 45 publications

Lactoferrin Is Broadly Active against Yeasts and Highly Synergistic with Amphotericin B

Lactoferrin Is Broadly Active against Yeasts and Highly Synergistic with Amphotericin B

Docking Prediction, Antifungal Activity, Anti-Biofilm Effects on Candida spp., and Toxicity against Human Cells of Cinnamaldehyde

Antifungal activity of 2-chloro-N-phenylacetamide, docking and molecular dynamics studies against clinical isolates of Candida tropicalis and Candida parapsilosis

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