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Biofilm-associated genes as potential molecular targets of nano-Fe3O4 in Candida albicans

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Abstract

Background

There are few effective treatments for Candida biofilm-associated infections. The present study demonstrated changes in the expression of biofilm-associated genes in Candida albicans treated with magnetic iron oxide nanoparticles (denoted as nano-Fe3O4).

Methods

Nano-Fe3O4 was biologically synthesized using Bacillus licheniformis, Bacillus cereus, and Fusarium oxysporum. Additionally, the biologically synthesized nano-Fe3O4 was characterized by visual observation; ultraviolet–visible spectroscopy, scanning electron microscopy, X-ray diffraction spectroscopy, and Fourier transform infrared spectroscopy. The biologically synthesized nano-Fe3O4 was tested for growth and biofilm formation in C. albicans. Furthermore, quantitative real-time reverse transcriptase–polymerase chain reaction (RT-PCR) was used to study the inhibition of biofilm-associated genes in C. albicans treated with nano-Fe3O4.

Results

The production of biologically synthesized nano-Fe3O4 was confirmed using extensive characterization methods. The nano-Fe3O4 inhibited growth and biofilm formation. Nano-Fe3O4 exhibited growth inhibition with minimum inhibition concentrations (MICs) of 50 to 200 μg mL−1. The anti-biofilm effects of nano-Fe3O4 were shown by 2,3-bis (2-methoxy-4-nitro-5 sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide (XTT) reduction assay, crystal violet staining, and light field microscopy. The gene expression results showed that the downregulation of BCR1, ALS1, ALS3, HWP1, and ECE1 genes inhibited the biofilm formation in C. albicans. ALS1 reduction was greater than others, with downregulation of 1375.83-, 1178.71-, and 768.47-fold at 2 × MIC, 1 × MIC, and ½ × MIC of nano-Fe3O4, respectively.

Conclusion

Biofilm-associated genes as potential molecular targets of nano-Fe3O4 in C. albicans may be an effective novel treatment strategy for biofilm-associated infections.

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Data availability

Data generated/analyzed during this study are included in the article and its supplementary information files or are available on request from the corresponding author.

Abbreviations

ALS :

Agglutinin-like protein

ANOVA:

Analysis of variance

BCR1 :

Biofilm and cell wall regulator 1

BRG1 :

Biofilm regulator 1

cDNA:

Complementary DNA

CDR1 :

Candida Drug resistance 1

CEK1-MAPK:

Candida albicans extracellular signal-regulated kinase 1-Mitogen-activated protein kinase

CV:

Crystal violet

EAP1 :

Enhanced adherence to polystyrene 1

ECE1 :

Extent of cell elongation 1

EFG1 :

Enhanced filamentous growth protein 1

ERG11 :

Ergosterol biosynthesis gene 11

FAV2 :

Factor activated 2

FCC:

Face-centered cubic

FDA:

Food and drug administration

FTIR:

Fourier transform infrared

GM:

Geometric mean

GSC1 :

Glucan synthase catalytic subunit 1

HWP1 :

Hyphal-specific wall protein 1

HYR1 :

Hyphally regulated 1

ICDD:

International centre of diffraction data

IFF :

Individual protein file family F

MDR1 :

Multidrug resistance 1

MFC:

Minimum fungicidal concentration

MIC:

Minimum inhibition concentration

MNN1 :

Mannosyl transferase 1

MSB2 :

Multicopy suppressor of bud emergence 2

NDT80 :

Non-dityrosine 80

ORF:

Open reading frame

PBS:

Phosphate-buffered saline

PGA :

Putative glycosylphosphatidylinositol-anchored proteins

Ras-cAMP-EFG1 :

Rat sarcoma- cyclic adenosine monophosphate-Enhanced filamentous growth protein 1

RCF:

Relative centrifugal force

ROB1 :

Regulator of biofilm 1

RPM:

Revolutions per minute

RPMI:

Roswell park memorial institute medium

RT-PCR:

Real-time reverse transcriptase–Polymerase chain reaction

SEM:

Scanning electron microscopy

SIM1 :

Secreted beta-glucosidase 1

TEC1 :

Transposon enhancement control 1

UV–Vis:

Ultraviolet–visible

XRD:

X-ray diffraction

XTT:

2,3-Bis (2-methoxy-4-nitro-5 sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide

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Acknowledgements

The authors wish to thank the Islamic Azad University of Shiraz for infrastructure facilities. The results presented in this study are part of a PhD thesis (IR.IAU.SHIRAZ.REC.1401.034).

Funding

This research received no external funding.

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Authors and Affiliations

  1. Department of Microbiology, Shiraz Branch, Islamic Azad University, Shiraz, Iran

    Mahbobeh Baghiat Esfahani & Nima Bahador

  2. Department of Biology, Gachsaran Branch, Islamic Azad University, Gachsaran, Iran

    Alireza Khodavandi & Fahimeh Alizadeh

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  1. Mahbobeh Baghiat Esfahani
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Contributions

AK, FA, and NB: made substantial contributions to the conception and design of the study. MBE, AK, and FA: conducted the search, analyzed the data, and wrote the manuscript. All authors read and approved the final content.

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Correspondence to Alireza Khodavandi.

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Baghiat Esfahani, M., Khodavandi, A., Alizadeh, F. et al. Biofilm-associated genes as potential molecular targets of nano-Fe3O4 in Candida albicans. Pharmacol. Rep 75, 682–694 (2023). https://doi.org/10.1007/s43440-023-00467-3

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