Immunometabolism in fungal infections: the need to eat to compete

Weerasinghe, Harshini; Traven, Ana

doi:10.1016/j.mib.2020.07.001

Cited by 26 publications

(24 citation statements)

References 67 publications

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“…Glucose metabolism involves in not only glycolysis but also pentose phosphate pathway (PPP), as well as cell wall biosynthesis in fungi ( Fleck et al., 2011 ; Oka et al., 2015 ). Recent studies have demonstrated the importance of glucose and glycolysis for host antifungal defenses against fungal infection ( Tucey et al., 2020 ; Weerasinghe and Traven, 2020 ). Maintaining host glucose homeostasis is important to prevent life-threatening fungal infection ( Tucey et al., 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Phosphoglucose Isomerase Plays a Key Role in Sugar Homeostasis, Stress Response, and Pathogenicity in Aspergillus flavus

Zhou

Odiba

et al. 2021

Front. Cell. Infect. Microbiol.

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Aspergillus flavus is one of the important human and plant pathogens causing not only invasive aspergillosis in immunocompromised patients but also crop contamination resulting from carcinogenic aflatoxins (AFs). Investigation of the targeting factors that are involved in pathogenicity is of unmet need to dismiss the hazard. Phosphoglucose isomerase (PGI) catalyzes the reversible conversion between glucose-6-phosphate and fructose-6-phosphate, thus acting as a key node for glycolysis, pentose phosphate pathway, and cell wall biosynthesis in fungi. In this study, we constructed an A. flavus pgi deletion mutant, which exhibited specific carbon requirement for survival, reduced conidiation, and slowed germination even under optimal experimental conditions. The Δpgi mutant lost the ability to form sclerotium and displayed hypersusceptibility to osmotic, oxidative, and temperature stresses. Furthermore, significant attenuated virulence of the Δpgi mutant was documented in the Caenorhabditis elegans infection model, Galleria mellonella larval model, and crop seeds. Our results indicate that PGI in A. flavus is a key enzyme in maintaining sugar homeostasis, stress response, and pathogenicity of A. flavus. Therefore, PGI is a potential target for controlling infection and AF contamination caused by A. flavus.

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Section: Discussionmentioning

confidence: 99%

Phosphoglucose Isomerase Plays a Key Role in Sugar Homeostasis, Stress Response, and Pathogenicity in Aspergillus flavus

Zhou

Odiba

et al. 2021

Front. Cell. Infect. Microbiol.

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“…The development of immunotherapeutic approaches to boost host defense is urgently needed to reduce the mortality of C. albicans BSI (Pfaller and Diekema, 2007). Although increased evidence supports the interconnection between immunometabolism and fungal infections, we are just beginning to understand the metabolic reprogramming associated with the monocyte immune response and its impact on host defense against fungal infections (Tucey et al, 2018;Weerasinghe and Traven, 2020). Here, we describe the changes in proteins and metabolites in human monocytes after stimulation with heat-inactivated C. albicans.…”

Section: Discussionmentioning

confidence: 99%

GLUT3 as an Intersection of Glycerophospholipid Metabolism and the Innate Immune Response to Candida albicans

Zhang

Yang

et al. 2021

Front. Cell. Infect. Microbiol.

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Immune cells can optimize the management of metabolic resources to balance their energy requirements in order to regulate immune responses. The interconnection between immunometabolism and fungal infections is becoming increasingly apparent. Using proteome and metabolome assays, we found that stimulation of primary human monocytes by Candida albicans was accompanied by upregulation of glucose transporter 3 (GLUT3) and activation of the glycerophospholipid metabolism pathway. Upregulated GLUT3 expression has been preliminarily confirmed in monocytes from patients with C. albicans bloodstream infection. Our findings support the importance of GLUT3 in the complex network of glycerophospholipid metabolism and the innate immune responses against C. albicans. In summary, this study might contribute to decipher the regulatory mechanism between the monocyte metabolic reprogramming and innate immune response and reveal potential targets for the antifungal treatments.

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“…Recognition of fungal cell wall components triggers glycolysis in innate immune cells [166][167][168][169]. This metabolic adaptation has been described in response to Candida albicans [166][167][168], Aspergillus fumigatus [170] and Cryptococcus gatti [171] infection.…”

Section: Fungimentioning

confidence: 97%

Lactate cross-talk in host–pathogen interactions

Llibre

Grudzinska

O’Shea

et al. 2021

Biochemical Journal

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Lactate is the main product generated at the end of anaerobic glycolysis or during the Warburg effect and its role as an active signalling molecule is increasingly recognised. Lactate can be released and used by host cells, by pathogens and commensal organisms, thus being essential for the homeostasis of host–microbe interactions. Infection can alter this intricate balance, and the presence of lactate transporters in most human cells including immune cells, as well as in a variety of pathogens (including bacteria, fungi and complex parasites) demonstrates the importance of this metabolite in regulating host–pathogen interactions. This review will cover lactate secretion and sensing in humans and microbes, and will discuss the existing evidence supporting a role for lactate in pathogen growth and persistence, together with lactate's ability to impact the orchestration of effective immune responses. The ubiquitous presence of lactate in the context of infection and the ability of both host cells and pathogens to sense and respond to it, makes manipulation of lactate a potential novel therapeutic strategy. Here, we will discuss the preliminary research that has been carried out in the context of cancer, autoimmunity and inflammation.

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Immunometabolism in fungal infections: the need to eat to compete

Cited by 26 publications

References 67 publications

Phosphoglucose Isomerase Plays a Key Role in Sugar Homeostasis, Stress Response, and Pathogenicity in Aspergillus flavus

Phosphoglucose Isomerase Plays a Key Role in Sugar Homeostasis, Stress Response, and Pathogenicity in Aspergillus flavus

GLUT3 as an Intersection of Glycerophospholipid Metabolism and the Innate Immune Response to Candida albicans

Lactate cross-talk in host–pathogen interactions

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