Repurposing pantoprazole and haloperidol as efflux pump inhibitors in azole resistant clinical Candida albicans and non-albicans isolates

El-Ganiny, Amira M.; Kamel, Hend A; Yossef, Nehal E.; Mansour, Basem; El-Baz, Ahmed M.

doi:10.1016/j.jsps.2022.01.011

Cited by 14 publications

(15 citation statements)

References 60 publications

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“…These findings support the worldwide shift of Candida infections in the last few decades towards NAC species. However, Kadry et al [13] and El-Ganiny et al [14] had reported lower prevalence of NACs of 42.6% and 29.3%, respectively.…”

Section: Discussionmentioning

confidence: 94%

Phenotypic identification and antifungal susceptibility patterns of Candida species isolated from various clinical specimens in Suez Canal University Hospitals

Aboueldahab

El-Sayed

Shehata

et al. 2023

Microbes and Infectious Diseases

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Background: Candida is the most common cause of fungal infections. Candida species are identified by different phenotypic methods. Accurate identification of Candida species enables appropriate selection of antifungal agents by clinicians. Azoles are the most frequently used antifungal drugs to treat Candida infections. However, resistance among previously susceptible Candida species has emerged which made antifungal susceptibility testing crucial. Aim: This study aimed to phenotypically identify the different Candida species isolated from various clinical specimens in Suez Canal University Hospitals (SCUHs), and to assess their antifungal susceptibility patterns. Method: One hundred and five clinical specimens were collected from different departments in SCUHs. Isolates were identified as Candida by colony morphology on Sabouraud dextrose agar and Gram staining. Candida species were phenotypically identified using germ tube test, hypertonic Sabouraud broth, corn meal agar, chromogenic Candida agar, KB006 HiCandida Identification Kit and Vitek 2 YST-ID system. Antifungal susceptibility to fluconazole, voriconazole and amphotericin B was done by disk diffusion method. Results: Prevalence of Candida was 54.3%. C. tropicalis was the most common species followed by C. albicans, C. dubliniensis, C. glabrata, C. parapsilosis and lastly C. kefyr. Only one strain was resistant to amphotericin B. Eight strains were susceptible dose dependent, and 2 were resistant to fluconazole. No resistance was detected to voriconazole. Conclusions: The prevalence of candidiasis is remarkable. Non-albicans Candida species (NACs) cause most of these infections. Fluconazole and amphotericin B showed low resistance rates. No resistance to voriconazole was reported in this study. Therefore, voriconazole could be more effective as empirical therapy than fluconazole and amphotericin B. Accurate identification of Candida species is essential for therapeutic and prognostic impact, appropriate selection of antifungal agents by clinicians and controlling the increase of resistant Candida strains.

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Section: Discussionmentioning

confidence: 94%

Phenotypic identification and antifungal susceptibility patterns of Candida species isolated from various clinical specimens in Suez Canal University Hospitals

Aboueldahab

El-Sayed

Shehata

et al. 2023

Microbes and Infectious Diseases

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“…The b§iofilm formation assay was carried out as previously described [ 20 ]. Briefly, overnight C. albicans cultures were diluted with SDB and adjusted to 1 × 10 6 CFU/mL.…”

Section: Methodsmentioning

confidence: 99%

Promising Antifungal Activity of Encephalartos laurentianus de Wild against Candida albicans Clinical Isolates: In Vitro and In Vivo Effects on Renal Cortex of Adult Albino Rats

Negm

El‐Aasr

Attia

et al. 2022

JoF

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Candida albicans can cause various infections, especially in immunocompromised patients. Its ability to develop resistance to the current antifungal drugs as well as its multiple virulence factors have rendered the problem even more complicated. Thus, in the present investigation, we elucidated an in vitro and in vivo antifungal activity of Encephalartos laurentianus methanol extract (ELME) against C. albicans clinical isolates for the first time. A phytochemical identification of 64 compounds was conducted in ELME using LC-MS/MS. Interestingly, ELME exhibited antifungal activity with MIC values that ranged from 32–256 µg/mL. Furthermore, we investigated the antibiofilm activity of ELME against the biofilms formed by C. albicans isolates. ELME displayed antibiofilm activity using a crystal violet assay as it decreased the percentages of cells, moderately and strongly forming biofilms from 62.5% to 25%. Moreover, the antibiofilm impact of ELME was elucidated using SEM and fluorescent microscope. A significant reduction in the biofilm formation by C. albicans isolates was observed. In addition, we observed that ELME resulted in the downregulation of the biofilm-related tested genes (ALS1, BCR1, PLB2, and SAP5) in 37.5% of the isolates using qRT-PCR. Besides, the in vivo antifungal activity of ELME on the kidney tissues of rats infected with C. albicans was investigated using histological and immunohistochemical studies. ELME was found to protect against C. albicans induced renal damage, decrease desmin and inducible nitric oxide synthase, increase alkaline phosphatase, and increase infected rats’ survival rate. Additionally, the cytotoxicity of ELME was elucidated on Human Skin Fibroblast normal cells using MTT assay. ELME had an IC50 of 31.26 µg/mL. Thus, we can conclude that ELME might be a promising future source for antifungal compounds.

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“…It was performed as described previously [ 4 ]. C. glabrata isolates were overnight grown on SDA then fungal suspensions (0.5 McFarland) were prepared.…”

Section: Methodsmentioning

confidence: 99%

“…qRT-PCR was accomplished using SensiFAST™ SYBR Green PCR Master Mix (Bioline, UK), as described by the manufacturer. The utilized primers are listed in Table S1 , using the URA3 gene as a reference gene [ 4 ]. Gene expression in C. glabrata isolates before treatment was considered to be one.…”

Section: Methodsmentioning

confidence: 99%

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Encephalartos villosus Lem. Displays a Strong In Vivo and In Vitro Antifungal Potential against Candida glabrata Clinical Isolates

Alqahtani

Elekhnawy

Negm

et al. 2022

JoF

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Recently, Candida glabrata has been recognized as one of the most common fungal species that is highly associated with invasive candidiasis. Its spread could be attributed to its increasing resistance to antifungal drugs. Thus, there is a high need for safer and more efficient therapeutic alternatives such as plant extracts. Here, we investigated the antifungal potential of Encephalartos villosus leaves methanol extract (EVME) against C. glabrata clinical isolates. Tentative phytochemical identification of 51 metabolites was conducted in EVME using LC–MS/MS. EVME demonstrated antifungal activity with minimum inhibitory concentrations that ranged from 32 to 256 µg/mL. The mechanism of the antifungal action was studied by investigating the impact of EVME on nucleotide leakage. Additionally, a sorbitol bioassay was performed, and we found that EVME affected the fungal cell wall. In addition, the effect of EVME was elucidated on the efflux activity of C. glabrata isolates using acridine orange assay and quantitative real-time PCR. EVME resulted in downregulation of the expression of the efflux pump genes CDR1, CDR2, and ERG11 in the tested isolates with percentages of 33.33%, 41.67%, and 33.33%, respectively. Moreover, we investigated the in vivo antifungal activity of EVME using a murine model with systemic infection. The fungal burden was determined in the kidney tissues. Histological and immunohistochemical studies were carried out to investigate the effect of EVME. We noticed that EVME reduced the congestion of the glomeruli and tubules of the kidney tissues of the rats infected with C. glabrata. Furthermore, it decreased both the proinflammatory cytokine tumor necrosis factor-alpha and the abnormal collagen fibers. Our results reveal, for the first time, the potential in vitro (by inhibition of the efflux activity) and in vivo (by decreasing the congestion and inflammation of the kidney tissues) antifungal activity of EVME against C. glabrata isolates.

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Repurposing pantoprazole and haloperidol as efflux pump inhibitors in azole resistant clinical Candida albicans and non-albicans isolates

Cited by 14 publications

References 60 publications

Phenotypic identification and antifungal susceptibility patterns of Candida species isolated from various clinical specimens in Suez Canal University Hospitals

Phenotypic identification and antifungal susceptibility patterns of Candida species isolated from various clinical specimens in Suez Canal University Hospitals

Promising Antifungal Activity of Encephalartos laurentianus de Wild against Candida albicans Clinical Isolates: In Vitro and In Vivo Effects on Renal Cortex of Adult Albino Rats

Encephalartos villosus Lem. Displays a Strong In Vivo and In Vitro Antifungal Potential against Candida glabrata Clinical Isolates

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