Growth, biofilm formation, antifungal susceptibility and oxidative stress resistance of Candida glabrata are affected by different glucose concentrations

Ng, Tzu Shan; Desa, Mohd Nasir Mohd; Sandai, Doblin; Chong, Pei Pei; Than, Leslie Thian Lung

doi:10.1016/j.meegid.2015.09.004

Cited by 30 publications

(25 citation statements)

References 41 publications

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“…11 In order to thrive in these changing nutrient environments, C. glabrata has evolved sophisticated regulatory mechanisms, including major metabolic changes that have been associated with virulence and, in particular, biofilm formation. 15,16,69 Once established, Candida biofilms are very difficult to eradicate due to their intrinsic tolerance to antifungals. In fact, azole resistance among Candida species, especially C. glabrata, is currently one of the greatest clinical challenges.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, low-glucose environments were found to induce the formation of C. glabrata biofilms and confer resistance to antifungal treatment. 15 This behavior suggests that this pathogen has the capacity to adjust its lifestyle in accordance to nutrient availability and determine the outcome of the next phase: either to continue as part of a biofilm population or disperse to find new colonization sites. However, little is known about the physiological effect of acidic environments, containing alternative non-fermentable carbon sources such as acetate, on the antifungal treatment of C. glabrata biofilms.…”

Section: Introductionmentioning

confidence: 99%

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Transcriptional responses of Candida glabrata biofilm cells to fluconazole are modulated by the carbon source

Alves

Kastora

Gomes-Gonçalves

et al. 2020

npj Biofilms Microbiomes

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Candida glabrata is an important human fungal pathogen known to trigger serious infections in immune-compromised individuals. Its ability to form biofilms, which exhibit high tolerance to antifungal treatments, has been considered as an important virulence factor. However, the mechanisms involving antifungal resistance in biofilms and the impact of host niche environments on these processes are still poorly defined. In this study, we performed a whole-transcriptome analysis of C. glabrata biofilm cells exposed to different environmental conditions and constraints in order to identify the molecular pathways involved in fluconazole resistance and understand how acidic pH niches, associated with the presence of acetic acid, are able to modulate these responses. We show that fluconazole treatment induces gene expression reprogramming in a carbon source and pH-dependent manner. This is particularly relevant for a set of genes involved in DNA replication, ergosterol, and ubiquinone biosynthesis. We also provide additional evidence that the loss of mitochondrial function is associated with fluconazole resistance, independently of the growth condition. Lastly, we propose that C. glabrata Mge1, a cochaperone involved in iron metabolism and protein import into the mitochondria, is a key regulator of fluconazole susceptibility during carbon and pH adaptation by reducing the metabolic flux towards toxic sterol formation. These new findings suggest that different host microenvironments influence directly the physiology of C. glabrata, with implications on how this pathogen responds to antifungal treatment. Our analyses identify several pathways that can be targeted and will potentially prove to be useful for developing new antifungals to treat biofilm-based infections.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transcriptional responses of Candida glabrata biofilm cells to fluconazole are modulated by the carbon source

Alves

Kastora

Gomes-Gonçalves

et al. 2020

npj Biofilms Microbiomes

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“…Glucose is commonly known as an important carbon source and energy for many organisms. Several studies have attempted to establish the linkage between glucose availability and physiological response of Candida species, including the biofilm formation, oxidative stress, and antifungal resistance (Rodaki et al, 2009 ; Uppuluri et al, 2010 ; Ene et al, 2012 ; Ng et al, 2015b ). The regulatory effect by glucose found in these studies is suggestive of the importance of glucose sensing and uptake mechanism in contributing to the fitness of Candida species.…”

Section: Introductionmentioning

confidence: 99%

SNF3 as High Affinity Glucose Sensor and Its Function in Supporting the Viability of Candida glabrata under Glucose-Limited Environment

Chew

Rangasamy

et al. 2015

Front. Microbiol.

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Candida glabrata is an emerging human fungal pathogen that has efficacious nutrient sensing and responsiveness ability. It can be seen through its ability to thrive in diverse range of nutrient limited-human anatomical sites. Therefore, nutrient sensing particularly glucose sensing is thought to be crucial in contributing to the development and fitness of the pathogen. This study aimed to elucidate the role of SNF3 (Sucrose Non Fermenting 3) as a glucose sensor and its possible role in contributing to the fitness and survivability of C. glabrata in glucose-limited environment. The SNF3 knockout strain was constructed and subjected to different glucose concentrations to evaluate its growth, biofilm formation, amphotericin B susceptibility, ex vivo survivability and effects on the transcriptional profiling of the sugar receptor repressor (SRR) pathway-related genes. The CgSNF3Δ strain showed a retarded growth in low glucose environments (0.01 and 0.1%) in both fermentation and respiration-preferred conditions but grew well in high glucose concentration environments (1 and 2%). It was also found to be more susceptible to amphotericin B in low glucose environment (0.1%) and macrophage engulfment but showed no difference in the biofilm formation capability. The deletion of SNF3 also resulted in the down-regulation of about half of hexose transporters genes (four out of nine). Overall, the deletion of SNF3 causes significant reduction in the ability of C. glabrata to sense limited surrounding glucose and consequently disrupts its competency to transport and perform the uptake of this critical nutrient. This study highlighted the role of SNF3 as a high affinity glucose sensor and its role in aiding the survivability of C. glabrata particularly in glucose limited environment.

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“…Depending on the carbon source used for growth, fungi also reshape their cell wall in order to improve osmotic resistance and elasticity (Ene IV, 2015). General adaptation mechanisms to stress, such as fungal growth, biofilm formation and antifungal susceptibility, are regulated in response to glucose as shown recently in C. glabrata (Ng et al, 2016).…”

Section: Sensing Of Nutrients In a Carbon Limited Environmentmentioning

confidence: 99%

Fungal sensing of host environment

Braunsdorf

Mailänder-Sánchez²,

Schaller

2016

Cellular Microbiology

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Summary To survive inside a host, fungi have to adapt to a changing and often hostile environment and therefore need the ability to recognize what is going on around them. To adapt to different host niches, they need to sense external conditions such as temperature, pH and to recognize specific host factors. The ability to respond to physiological changes inside the host, independent of being in a commensal, pathogenic or even symbiotic context, implicates mechanisms for sensing of specific host factors. Because the cell wall is constantly in contact with the surrounding, fungi express receptors on the surface of their cell wall, such as pheromone receptors, which have important roles, besides mediating chemotropism for mating. We are not restricting the discussion to the human host because the receptors and mechanisms used by different fungal species to sense their environment are often similar even for plant pathogens. Furthermore, the natural habitat of opportunistic pathogenic fungi with the potential to cause infection in a human host is in soil and on plants. While the hosts' mechanisms of sensing fungal pathogens have been addressed in the literature, the focus of this review is to fill the gap, giving an overview on fungal sensing of a host‐(ile) environment. Expanding our knowledge on host–fungal interactions is extremely important to prevent and treat diseases of pathogenic fungi, which are important issues in human health and agriculture but also to understand the delicate balance of fungal symbionts in our ecosystem.

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Growth, biofilm formation, antifungal susceptibility and oxidative stress resistance of Candida glabrata are affected by different glucose concentrations

Cited by 30 publications

References 41 publications

Transcriptional responses of Candida glabrata biofilm cells to fluconazole are modulated by the carbon source

Transcriptional responses of Candida glabrata biofilm cells to fluconazole are modulated by the carbon source

SNF3 as High Affinity Glucose Sensor and Its Function in Supporting the Viability of Candida glabrata under Glucose-Limited Environment

Fungal sensing of host environment

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