Regulatory Role of ERG3 and Efg1 in Azoles-Resistant Strains of Candida albicans Isolated from Patients Diagnosed with Vulvovaginal Candidiasis

Feng, Wenli; Yang, Jing; Xi, Zhiqin; Ji, Ying; Zhu, Xin; Yang, Lu; Ma, Yan

doi:10.1007/s12088-019-00833-x

Cited by 12 publications

(9 citation statements)

References 26 publications

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“…Therefore, combination therapy, while reducing the overuse of drugs, may give a suitable approach for combating resistance against commonly used antifungals. Furthermore, the synergistic effect of Ag NPs and azoles (a class of antifungals) against FLZ nonresponsive C. albicans has been discussed by researchers [ 6 , 68 ]. In the present work, we also observed that Ag-Ni NPs work synergistically with FLZ and made FLZ nonresponsive C. albicans cells susceptible to FLZ treatment.…”

Section: Resultsmentioning

confidence: 99%

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Combination Effect of Novel Bimetallic Ag-Ni Nanoparticles with Fluconazole against Candida albicans

Kamli

Alzahrani

Albukhari

et al. 2022

JoF

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The increasing frequency of antifungal drug resistance among pathogenic yeast “Candida” has posed an immense global threat to the public healthcare sector. The most notable species of Candida causing most fungal infections is Candida albicans. Furthermore, recent research has revealed that transition and noble metal combinations can have synergistic antimicrobial effects. Therefore, a one-pot seedless biogenic synthesis of Ag-Ni bimetallic nanoparticles (Ag–Ni NPs) using Salvia officinalis aqueous leaf extract is described. Various techniques, such as UV–vis, FTIR, XRD, SEM, EDX, and TGA, were used to validate the production of Ag-Ni NPs. The antifungal susceptibility of Ag-Ni NPs alone and in combination with fluconazole (FLZ) was tested against FLZ-resistant C. albicans isolate. Furthermore, the impacts of these NPs on membrane integrity, drug efflux pumps, and biofilms formation were evaluated. The MIC (1.56 μg/mL) and MFC (3.12 μg/mL) results indicated potent antifungal activity of Ag-Ni NPs against FLZ-resistant C. albicans. Upon combination, synergistic interaction was observed between Ag-Ni NPs and FLZ against C. albicans 5112 with a fractional inhibitory concentration index (FICI) value of 0.31. In-depth studies revealed that Ag-Ni NPs at higher concentrations (3.12 μg/mL) have anti-biofilm properties and disrupt membrane integrity, as demonstrated by scanning electron microscopy results. In comparison, morphological transition was halted at lower concentrations (0.78 μg/mL). From the results of efflux pump assay using rhodamine 6G (R6G), it was evident that Ag-Ni NPs blocks the efflux pumps in the FLZ-resistant C. albicans 5112. Targeting biofilms and efflux pumps using novel drugs will be an alternate approach for combatting the threat of multi-drug resistant (MDR) stains of C. albicans. Therefore, this study supports the usage of Ag-Ni NPs to avert infections caused by drug resistant strains of C. albicans.

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Section: Resultsmentioning

confidence: 99%

“…Several metals, including silver, cobalt, nickel, and palladium, have been examined in the form of NPs. They have distinctive properties that have pushed their use in various applications [ 6 , 7 , 8 , 9 ]. Metallic nanoparticles have a wide range of biological, catalytic, and electrochemical applications [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Combination Effect of Novel Bimetallic Ag-Ni Nanoparticles with Fluconazole against Candida albicans

Kamli

Alzahrani

Albukhari

et al. 2022

JoF

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“…Indeed, various multi-drug resistant, especially uconazole resistant C. albicans have been reported [9]. So, it is exigent to search for newer and more effective therapeutics [10]. In the last decade, much progress has been made in understanding the reasons responsible for antifungal resistance in C. albicans.…”

Section: Introductionmentioning

confidence: 99%

Silver nanoparticles offer a synergistic effect with fluconazole against fluconazole-resistant Candida albicans by abrogating drug efflux pumps and increasing endogenous ROS

Jia

Sun

2021

Infection, Genetics and Evolution

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Objectives: A frequent emergence of drug resistance has been observed and posed great threat to global public health recently. This work aimed to investigate the potential synergistic effect and the underlying mechanisms of AgNPs-uconazole combination more extensively through 2 clinically isolated uconazole-resistant Candida albicans (C. albicans) strains.Methods: Antifungal properties of AgNPs and uconazole alone or together against planktonic cells and bio lms were tested. Cellular and molecular targets associated with uconazole resistance were monitored after AgNPs treatment. Antifungal potential of AgNPs-uconazole combination was also explored in vivo using a mouse model of disseminated candidiasis. Tissue burden and survival rate were analyzed.Results: The results indicated that AgNPs worked synergistically with uconazole against both planktonic cells of uconazole-resistant C. albicans and bio lms formed < 12 hours. AgNPs treatment downregulated ERG1, ERG11, ERG25, and CDR2, decreased membrane ergosterol levels and membrane uidity, reduced membrane content of Cdr1p, Cdr2p, and thus e ux bump activity. The elevated ROS production was also a likely cause of the synergistic effect. In vivo, AgNPs and uconazole combination signi cantly decreased the fungal burden and improved the survival rate of infected mice. Conclusion:In conclusion, these results further con rm that AgNPs-uconazole combination is a hopeful strategy for the treatment of uconazole-resistant fungal infections.

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“…Previous study has implied that the drug resistance of C. albicans is a complex process involving multiple mechanisms 18,31 …”

Section: Discussionmentioning

confidence: 99%

“…Previous study has implied that the drug resistance of C. albicans is a complex process involving multiple mechanisms. 18 , 31 ERG11 has been proved to play an important role in drug resistance. We sequenced ERG11 gene in the all clinical strains, and found 17 kinds of synonymous mutations and 6 kinds of missense mutations.…”

Section: Discussionmentioning

confidence: 99%

The effects of secreted aspartyl proteinase inhibitor ritonavir on azoles‐resistant strains of Candida albicans as well as regulatory role of SAP2 and ERG11

Feng

Yang

et al. 2021

Immunity Inflam & Disease

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Background Candida albicans, the main human fungal pathogen, can cause fungal infection and seriously affect people's health and life. This study aimed to investigate the effects of ritonavir (RIT) on C. albicans and the correlation between SAP2 as well as ERG11 and drug resistance. Results Secreted aspartyl proteinases (Saps) activities and pathogenicity of C. albicans with different drug resistance were measured. M27‐A4 broth microdilution method was used to analyze the drug sensitivity of RIT combined with fluconazole (FCA) on C. albicans. After that, SAP2 and ERG11 mutations were examined by polymerase chain reaction (PCR) and sequencing, and quantitative real‐time PCR was utilized to determine the expression of the two genes. By analyzing pz values, the Saps activity of cross‐resistant strains was the highest, followed by voriconazole (VRC)‐resistant strains, FCA‐resistant strains, itraconazole (ITR)‐resistant strains, and sensitive strains. The pathogenicity of C. albicans in descending order was as follows: cross‐resistant strains, VRC‐resistant strains, ITR‐resistant strains, FCA‐resistant strains, and sensitive strains. With the increase of RIT concentrations, the Saps activity was gradually inhibited. Drug sensitivity results showed that there was no synergistic effect between RIT and FCA. Additionally, no gene mutation sites were found in SAP2 sequencing, and 17 synonymous mutations and 6 missense mutations occurred in ERG11 sequencing. Finally, the expression of SAP2 and ERG11 was significantly higher in the resistant strains compared with the sensitive strains, and there was a positive liner correlation between SAP2 and ERG11 messenger RNA expression (r = .6655, p < .001). Conclusion These findings may help to improve our understanding of azole‐resistant mechanisms of C. albicans and provide a novel direction for clinical therapeutics of C. albicans infection.

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Regulatory Role of ERG3 and Efg1 in Azoles-Resistant Strains of Candida albicans Isolated from Patients Diagnosed with Vulvovaginal Candidiasis

Cited by 12 publications

References 26 publications

Combination Effect of Novel Bimetallic Ag-Ni Nanoparticles with Fluconazole against Candida albicans

Combination Effect of Novel Bimetallic Ag-Ni Nanoparticles with Fluconazole against Candida albicans

Silver nanoparticles offer a synergistic effect with fluconazole against fluconazole-resistant Candida albicans by abrogating drug efflux pumps and increasing endogenous ROS

The effects of secreted aspartyl proteinase inhibitor ritonavir on azoles‐resistant strains of Candida albicans as well as regulatory role of SAP2 and ERG11

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