“Under Pressure” – How fungi evade, exploit, and modulate cells of the innate immune system

Lange, Theresa; Kasper, Lydia; Gresnigt, Mark S.; Brunke, Sascha; Hube, Bernhard

doi:10.1016/j.smim.2023.101738

Cited by 5 publications

(9 citation statements)

References 277 publications

(405 reference statements)

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“…Hyphae‐associated superoxide dismutase 5 (SOD5) is useful to counter the oxidative stress (produced by immune cells or drugs). In addition, the toxin candidalysin secreted by hyphae can cause macrophage death and tissue damages 6,37 . In this scenario, the ability of FN to impede hyphal growth indicates its potential to block C. albicans invasion in tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Besides Candidaemia, C. albicans can also cause mucosal infections such as oral thrush and vulvovaginal candidiasis, although this fungus belongs to one of the commensal fungi residing in gastrointestinal and vaginal tracts 2 . The pathogenicity of C. albicans is closely associated with its ability to form hypha, which enables its difficulty to be engulfed by and easy escape from phagocytes, even death of phagocytes 6 . C. albicans hyphae also express superoxide dismutase 5 (SOD5) that detoxifies reactive oxygen species (ROS), and secret pore‐forming candidalysin that damages tissues 6 .…”

Section: Introductionmentioning

confidence: 99%

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Fangchinoline inhibits growth and biofilm of Candida albicans by inducing ROS overproduction

Yang,

Wang,

et al. 2024

J Cellular Molecular Medi

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Infections caused by Candida species, especially Candida albicans, threaten the public health and create economic burden. Shortage of antifungals and emergence of drug resistance call for new antifungal therapies while natural products were attractive sources for developing new drugs. In our study, fangchinoline, a bis‐benzylisoquinoline alkaloid from Chinese herb Stephania tetrandra S. Moore, exerted antifungal effects on planktonic growth of several Candida species including C. albicans, with MIC no more than 50 μg/mL. In addition, results from microscopic, MTT and XTT reduction assays showed that fangchinoline had inhibitory activities against the multiple virulence factors of C. albicans, such as adhesion, hyphal growth and biofilm formation. Furthermore, this compound could also suppress the metabolic activity of preformed C. albicans biofilms. PI staining, followed by confocal laser scanning microscope (CLSM) analysis showed that fangchinoline can elevate permeability of cell membrane. DCFH‐DA staining suggested its anti‐Candida mechanism also involved overproduction of intracellular ROS, which was further confirmed by N‐acetyl‐cysteine rescue tests. Moreover, fangchinoline showed synergy with three antifungal drugs (amphotericin B, fluconazole and caspofungin), further indicating its potential use in treating C. albicans infections. Therefore, these results indicated that fangchinoline could be a potential candidate for developing anti‐Candida therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fangchinoline inhibits growth and biofilm of Candida albicans by inducing ROS overproduction

Yang,

Wang,

et al. 2024

J Cellular Molecular Medi

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“…Immune evasion is a first strategy to avoid phagocytosis (reviewed, e.g., in Lange et al, 2023). One approach to counteract antimicrobial activities in early stages of infections is to hide the PAMPs, the pathogen-associated molecular patterns on the fungal surface, from immune detection.…”

Section: Avoiding Phagocytosismentioning

confidence: 99%

“…Overall, fungi that persist intracellularly pose a threat to humans as they can exploit phagocytes to evade the immune system, to disseminate undetected to other organs (Lange et al, 2023), and to serve as a starting point for causing reinfections of the host (Brunet et al, 2018).…”

Section: Recently Discovered Persistersmentioning

confidence: 99%

“…As described above, several airborne fungal pathogens can make phagocytes their home for long periods of time. In recent years, it has been suggested that C. glabrata , a commensal fungus, could employ a similar strategy by using macrophages as a persistence niche (Kasper et al, 2015; Lange et al, 2023). Unlike the filamenting C. albicans , C. glabrata replicates as a yeast cell and can persist inside the phagocytes for several days (Rai et al, 2013; Roetzer et al, 2010; Seider et al, 2011).…”

Section: Persistencementioning

confidence: 99%

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“We've got to get out”—Strategies of human pathogenic fungi to escape from phagocytes

Sonnberger,

Kasper,

Lange

et al. 2023

Molecular Microbiology

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Human fungal pathogens are a deadly and underappreciated risk to global health that most severely affect immunocompromised individuals. A virulence attribute shared by some of the most clinically relevant fungal species is their ability to survive inside macrophages and escape from these immune cells. In this review, we discuss the mechanisms behind intracellular survival and elaborate how escape is mediated by lytic and non‐lytic pathways as well as strategies to induce programmed host cell death. We also discuss persistence as an alternative to rapid host cell exit. In the end, we address the consequences of fungal escape for the host immune response and provide future perspectives for research and development of targeted therapies.

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Bibliometric analysis and thematic review of Candida pathogenesis: Fundamental omics to applications as potential antifungal drugs and vaccines

Lim,

Muhd Noor,

Sabri

et al. 2023

Medical Mycology

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Invasive candidiasis caused by the pathogenic Candida yeast species has resulted in elevating global mortality. The pathogenicity of Candida spp. is not only originated from its primary invasive yeast-to-hyphal transition; virulence factors (transcription factors, adhesins, invasins, and enzymes), biofilm, antifungal drug resistance, stress tolerance, and metabolic adaptation have also contributed to a greater clinical burden. However, the current research theme in fungal pathogenicity could hardly be delineated with the increasing research output. Therefore, our study analyzed the research trends in Candida pathogenesis over the past 37 years via a bibliometric approach against the Scopus and Web of Science databases. Based on the 3993 unique documents retrieved, significant international collaborations among researchers were observed, especially between Germany (Bernhard Hube) and the UK (Julian Naglik) whose focuses are on Candida proteinases, adhesins, and Candidalysin. The prominent researchers (Neils Gow, Alistair Brown and Frank Odds) at the University of Exeter and University of Aberdeen (second top performing affiliation), UK contribute significantly to the mechanisms of Candida adaptation, tolerance, and stress response. However, the science mapping of co-citation analysis performed herein could not identify a hub representative of subsequent work since the clusters were semi-redundant. The co-word analysis that was otherwise adopted, revealed three research clusters; the cluster-based thematic analyses indicated the severeness of Candida biofilm and antifungal resistance as well as the elevating trend on molecular mechanism elucidation for drug screening and repurposing. Importantly, the in vivo pathogen adaptation and interactions with hosts are crucial for potential vaccine development.

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“Under Pressure” – How fungi evade, exploit, and modulate cells of the innate immune system

Cited by 5 publications

References 277 publications

Fangchinoline inhibits growth and biofilm of Candida albicans by inducing ROS overproduction

Fangchinoline inhibits growth and biofilm of Candida albicans by inducing ROS overproduction

“We've got to get out”—Strategies of human pathogenic fungi to escape from phagocytes

Bibliometric analysis and thematic review of Candida pathogenesis: Fundamental omics to applications as potential antifungal drugs and vaccines

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