Riboflavin Targets the Cellular Metabolic and Ribosomal Pathways of Candida albicans
            <i>In Vitro</i>
            and Exhibits Efficacy against Oropharyngeal Candidiasis

Lei, Junwen; Huang, Jian; Xin, Caiyan; Liu, Fangyan; Zhang, Jinping; Xie, Yuxin; Mao, Yihua; Chen, Wenbi; Song, Zhimin

doi:10.1128/spectrum.03801-22

Cited by 8 publications

(4 citation statements)

References 65 publications

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“…To further explore the structural damage caused by VD3, C. neoformans cell membrane permeability was evaluated by PI staining. In principle, PI can permeate damaged fungal cell membranes, bind to nucleic acids, and emit red fluorescence [28]. As shown in Figure 4A,B, the untreated fungal cells did not emit red fluorescence, whereas the VD3-treated fungal cells emitted strong red fluorescence, with the fluorescence intensity increasing.…”

Section: Vd3-altered Cell Membrane Permeability Of C Neoformansmentioning

confidence: 91%

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Antifungal Effect of Vitamin D3 against Cryptococcus neoformans Coincides with Reduced Biofilm Formation, Compromised Cell Wall Integrity, and Increased Generation of Reactive Oxygen Species

Huang

Lei

et al. 2023

JoF

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Cryptococcus neoformans is an invasive fungus that causes both acute and chronic infections, especially in immunocompromised patients. Owing to the increase in the prevalence of drug-resistant pathogenic fungi and the limitations of current treatment strategies, drug repositioning has become a feasible strategy to accelerate the development of new drugs. In this study, the minimum inhibitory concentration of vitamin D3 (VD3) against C. neoformans was found to be 0.4 mg/mL by broth microdilution assay. The antifungal activities of VD3 were further verified by solid dilution assays and “time-kill” curves. The results showed that VD3 reduced fungal cell adhesion and hydrophobicity and inhibited biofilm formation at various developmental stages, as confirmed by crystal violet staining and the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay. Fluorescence staining of cellular components and a stress susceptibility assay indicated that VD3 compromised cell integrity. Reverse transcription quantitative PCR demonstrated that VD3 treatment upregulated the expression of fungal genes related to cell wall synthesis (i.e., CDA3, CHS3, FKS1, and AGS1). Moreover, VD3 enhanced cell membrane permeability and caused the accumulation of intracellular reactive oxygen species. Finally, VD3 significantly reduced the tissue fungal burden and prolonged the survival of Galleria mellonella larvae infected with C. neoformans. These results showed that VD3 could exert significant antifungal activities both in vitro and in vivo, demonstrating its potential application in the treatment of cryptococcal infections.

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Section: Vd3-altered Cell Membrane Permeability Of C Neoformansmentioning

confidence: 91%

“…The primers used in this study are listed in Supplemental Table S1. The relative expression levels of genes were calculated using 2 −∆∆CT method against glycerol-3-phosphate dehydrogenase 1 (GPD1) as the housekeeping gene [24,28].…”

Section: Rna Isolation and Reverse Transcription Quantitative Pcrmentioning

confidence: 99%

Antifungal Effect of Vitamin D3 against Cryptococcus neoformans Coincides with Reduced Biofilm Formation, Compromised Cell Wall Integrity, and Increased Generation of Reactive Oxygen Species

Huang

Lei

et al. 2023

JoF

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“…Invasive pathogens often occur in people with compromised immunity (Xie et al 2022 ). Therefore, antifungal agents could act by either having a direct antifungal (fungicidal or fungistatic) effect on pathogenic fungi or playing a role in upregulating a patient’s immunity (Arastehfar et al 2020 ; Lei et al 2023 , 2022 ). There is an urgent need to develop new antifungal drugs, drugs that help to increase the activity of existing antifungal drugs, or drugs with immunomodulatory effects on the host.…”

Section: Introductionmentioning

confidence: 99%

The potential role of plant secondary metabolites on antifungal and immunomodulatory effect

Zhou

Zeng

Huang

et al. 2023

Appl Microbiol Biotechnol

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With the widespread use of antibiotic drugs worldwide and the global increase in the number of immunodeficient patients, fungal infections have become a serious threat to global public health security. Moreover, the evolution of fungal resistance to existing antifungal drugs is on the rise. To address these issues, the development of new antifungal drugs or fungal inhibitors needs to be targeted urgently. Plant secondary metabolites are characterized by a wide variety of chemical structures, low price, high availability, high antimicrobial activity, and few side effects. Therefore, plant secondary metabolites may be important resources for the identification and development of novel antifungal drugs. However, there are few studies to summarize those contents. In this review, the antifungal modes of action of plant secondary metabolites toward different types of fungi and fungal infections are covered, as well as highlighting immunomodulatory effects on the human body. This review of the literature should lay the foundation for research into new antifungal drugs and the discovery of new targets. Key points • Immunocompromised patients who are infected the drug-resistant fungi are increasing. • Plant secondary metabolites toward various fungal targets are covered. • Plant secondary metabolites with immunomodulatory effect are verified in vivo.

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“…Besides them, metabolism-based resistance has been recently documented (Peng et al, 2015a , b ; Lopatkin et al, 2021 ; Fan et al, 2023 ; Jiang et al, 2023 ), indicating that metabolic adaptation may represent a class of resistance mechanisms by which cells alter their metabolic response to mitigate downstream toxic aspects of antibiotic lethality (Lopatkin et al, 2021 ). A metabolic state-reprogramming system can be developed to reverse antibiotic resistance (Peng et al, 2015a , b ; Cheng et al, 2019 ; Zhao et al, 2021 ; Zhou et al, 2022 ; Chen et al, 2023 ; Lei et al, 2023 ). Therefore, further exploration of the metabolic mechanism of antibiotic resistance is helpful in developing previously unknown approaches to eliminate antibiotic-resistant pathogens (Peng et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

A glucose-mediated antibiotic resistance metabolic flux from glycolysis, the pyruvate cycle, and glutamate metabolism to purine metabolism

Xiang,

Wang,

Tao

et al. 2023

Front. Microbiol.

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IntroductionBacterial metabolic environment influences antibiotic killing efficacy. Thus, a full understanding for the metabolic resistance mechanisms is especially important to combat antibiotic-resistant bacteria.MethodsIsobaric tags for relative and absolute quantification-based proteomics approach was employed to compare proteomes between ceftazidime-resistant and -sensitive Edwarsiella tarda LTB4 (LTB4-RCAZ and LTB4-S, respectively).ResultsThis analysis suggested the possibility that the ceftazidime resistance mediated by depressed glucose is implemented through an inefficient metabolic flux from glycolysis, the pyruvate cycle, glutamate metabolism to purine metabolism. The inefficient flux was demonstrated by the reduced expression of genes and the decreased activity of enzymes in the four metabolic pathways. However, supplement upstream glucose and downstream guanosine separately restored ceftazidime killing, which not only supports the conclusion that the inefficient metabolic flux is responsible for the resistance, but also provides an effective approach to reverse the resistance. In addition, the present study showed that ceftazidime is bound to pts promoter in E. tarda.DiscussionOur study highlights the way in fully understanding metabolic resistance mechanisms and establishing metabolites-based metabolic reprogramming to combat antibiotic resistance.

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Riboflavin Targets the Cellular Metabolic and Ribosomal Pathways of Candida albicans In Vitro and Exhibits Efficacy against Oropharyngeal Candidiasis

Abstract: Candida species are common pathogens in fungal infections, causing mucosal infection and invasive infection in immunodeficient patients. Given the limited classes of drugs and resistance to these drugs, new antifungal agents need to be developed.

Cited by 8 publications

References 65 publications

Antifungal Effect of Vitamin D3 against Cryptococcus neoformans Coincides with Reduced Biofilm Formation, Compromised Cell Wall Integrity, and Increased Generation of Reactive Oxygen Species

Antifungal Effect of Vitamin D3 against Cryptococcus neoformans Coincides with Reduced Biofilm Formation, Compromised Cell Wall Integrity, and Increased Generation of Reactive Oxygen Species

The potential role of plant secondary metabolites on antifungal and immunomodulatory effect

A glucose-mediated antibiotic resistance metabolic flux from glycolysis, the pyruvate cycle, and glutamate metabolism to purine metabolism

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