Antifungal drug resistance in oral Candida isolates from HIV-infected and healthy individuals and efficacy of chitosan as an alternative antifungal agent

Thanyasrisung, Panida; Satitviboon, Wuttika; Howattanapanich, Sukanya; Matangkasombut, Oranart

doi:10.1016/j.archoralbio.2023.105628

Cited by 3 publications

(10 citation statements)

References 37 publications

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“…Chitosan has broad applications in medical and cosmetics industries because of its high biocompatibility, biodegradability and antibacterial and antifungal activities [ 7 ]. We previously reported chitosan derivatives that are effective against common oral Candida species, including clinical isolates and biofilms [ 9 , 10 , 20 ]. Importantly, oligomer and polymer chitosan were effective against most fluconazole-resistant isolates from HIV-infected individuals, emphasizing their potential as a promising antifungal agent against azole-resistant Candida [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…We previously reported chitosan derivatives that are effective against common oral Candida species, including clinical isolates and biofilms [ 9 , 10 , 20 ]. Importantly, oligomer and polymer chitosan were effective against most fluconazole-resistant isolates from HIV-infected individuals, emphasizing their potential as a promising antifungal agent against azole-resistant Candida [ 10 ]. Furthermore, chitosan can serve as an active carrier to deliver and enhance the activity of antimicrobial drugs, and its mucoadhesive property can provide retention on the mucosa or under denture to prevent or treat denture stomatitis [ 7 , 9 ].…”

Section: Discussionmentioning

confidence: 99%

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Effects of efflux pumps on antifungal activity of chitosan against Candida albicans

Muangsawat,

Chaiyosang,

Sinkanarak

et al. 2024

Journal of Oral Microbiology

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Background Antifungal resistance is a major problem, commonly caused by drug-efflux pump overexpression. To evaluate if chitosan could be effective in drug-resistant Candida infections, we investigated the effects of efflux pumps on antifungal activity of chitosan. Materials and Methods The minimal fungicidal concentration (MFC) of oligomer (7–9 kD) and polymer (900–1,000 kD) chitosan against Saccharomyces cerevisiae and Candida albicans were evaluated by broth and agar dilution methods. The MFCs of S. cerevisiae with single deletion of efflux pump genes, with deletion of seven efflux pumps ( AD∆ ), and AD∆ overexpressing C. albicans efflux pump genes ( CDR1 , CDR2 and MDR1 ) were determined. C. albicans with homozygous deletions of CDR1 and of CDR2 were generated using CRISPR-Cas9 system and tested for chitosan susceptibility. Results While deleting any individual efflux pump genes had no effect on chitosan susceptibility, simultaneous deletion of multiple pumps (in AD∆ ) increased sensitivity to both types of chitosan. Interestingly, the overexpression of CDR1 , CDR2 or MDR1 in AD∆ barely affected its sensitivity. Moreover, C. albicans with homozygous deletions of CDR1 and/or CDR2 showed similar sensitivity to wildtype. Conclusion Thus, C. albicans susceptibility to chitosan was not affected by drug-efflux pumps. Chitosan may be a promising antifungal agent against pump-overexpressing azole-resistant C . albicans .

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of efflux pumps on antifungal activity of chitosan against Candida albicans

Muangsawat,

Chaiyosang,

Sinkanarak

et al. 2024

Journal of Oral Microbiology

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“…Candidiasis is a common opportunistic infection in HIV-infected patients [1]. There has been a gradual emergence of non-albicans Candida (NCAC) species as a cause of refractory mucosal and invasive candidiasis, particularly in patients with advanced immunosuppression, and the resistance to antifungal agents in the Candida species (particularly to azoles) is a point of concern [2][3][4]. Predisposing factors include age (children or older people), smoking, diabetes mellitus, nutritional disorders, endocrinopathies, immunosuppressive conditions (e.g., chemotherapy) and malignancies (e.g., cancer) [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

“…In the past, oropharyngeal candidiasis (OC) was used as a way to diagnose AIDS by being one of the first clinical signs of this disease, affecting 50 to 95% of HIV-positive individuals [2][3][4][5][6]. OC can cause dysphagia, odynophagia, retrosternal chest pain and extreme weight loss [4].…”

Section: Introductionmentioning

confidence: 99%

Antifungal Susceptibility and Candida sp. Biofilm Production in Clinical Isolates of HIV-Positive Brazilian Patients under HAART Therapy

Alves,

de Brito,

de Araújo

et al. 2024

Biomedicines

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The aim of the present study was to characterize biofilms formed by Candida spp. clinical isolates (n = 19), isolated from the oral mucosa of HIV-positive patients. For characterizing the biofilms formed by several Candida sp. strains, isolated from HIV-positive patients, in terms of formed biomass, matrix composition and antifungal susceptibility profile, clinical isolates (n = 19) were collected from oral mucosa and identified. The biofilm of the samples was cultured with fluconazole (1250 mg/L), voriconazole (800 mg/L), anidulafungin (2 mg/L) or amphotericin B (2 mg/L). Afterwards, the quantification of the total biomass was performed using crystal violet assay, while the proteins and carbohydrates levels were quantified in the matrix. The results showed a predominance of C. albicans, followed by C. krusei. Around 58% of the Candida spp. biofilm had susceptibility to fluconazole and voriconazole (800 mg/L), 53% to anidulafungin and 74% to amphotericin B. C. krusei presented both the lowest and the highest biofilm matrix contents in polysaccharides and proteins. The low resistance to antifungal agents reported here was probably due to the fact that none of the participants had a prolonged exposure to these antifungals. A predominance of less virulent Candida spp. strains with low or no resistance to antifungals was observed. This can be attributed to a low fungal selective pressure. This most probably happened due to a low fungal selective pressure but also due to a good adherence to HAART therapy, which guarantees a stable and stronger immune patient response.

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“…Fungal invasive infections are associated with a wide range of side effects and high mortality rates, especially in immunocompromised patients [ 1 , 2 , 3 , 4 ]. Amphotericin B (AmB) remains the gold standard in the therapy of serious systemic fungal diseases due to its broad activity spectrum, low resistance, and high clinical efficacy [ 5 , 6 , 7 ] in various cases including post-COVID fungal infections [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Triggering the Amphotericin B Pore-Forming Activity by Phytochemicals

2023

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The macrolide polyene antibiotic amphotericin B (AmB), remains a valuable drug to treat systemic mycoses due to its wide antifungal activity and low probability of developing resistance. The high toxicity of AmB, expressed in nephropathy and hemolysis, could be partially resolved by lowering therapeutic AmB concentration while maintaining efficacy. This work discusses the possibility of using plant polyphenols and alkaloids to enhance the pore-forming and consequently antifungal activity of AmB. We demonstrated that phloretin, phlorizin, naringenin, taxifolin, quercetin, biochanin A, genistein, resveratrol, and quinine led to an increase in the integral AmB-induced transmembrane current in the bilayers composed of palmitoyloleoylphosphocholine and ergosterol, while catechin, colchicine, and dihydrocapsaicin did not practically change the AmB activity. Cardamonin, 4′-hydroxychalcone, licochalcone A, butein, curcumin, and piperine inhibited AmB-induced transmembrane current. Absorbance spectroscopy revealed no changes in AmB membrane concentration with phloretin addition. A possible explanation of the potentiation is related to the phytochemical-produced changes in the elastic membrane properties and the decrease in the energy of formation of the lipid mouth of AmB pores, which is partially confirmed by differential scanning microcalorimetry. The possibility of AmB interaction with cholesterol in the mammalian cell membranes instead of ergosterol in fungal membranes, determines its high toxicity. The replacement of ergosterol with cholesterol in the membrane lipid composition led to a complete loss or a significant decrease in the potentiating effects of tested phytochemicals, indicating low potential toxicity of these compounds and high therapeutic potential of their combinations with the antibiotic. The discovered combinations of AmB with plant molecules that enhance its pore-forming ability in ergosterol-enriched membranes, seem to be promising for further drug development in terms of the toxicity decrease and efficacy improvement.

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Antifungal drug resistance in oral Candida isolates from HIV-infected and healthy individuals and efficacy of chitosan as an alternative antifungal agent

Cited by 3 publications

References 37 publications

Effects of efflux pumps on antifungal activity of chitosan against Candida albicans

Effects of efflux pumps on antifungal activity of chitosan against Candida albicans

Antifungal Susceptibility and Candida sp. Biofilm Production in Clinical Isolates of HIV-Positive Brazilian Patients under HAART Therapy

Triggering the Amphotericin B Pore-Forming Activity by Phytochemicals

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