Echinocandin Treatment of Candida albicans Biofilms Enhances Neutrophil Extracellular Trap Formation

Hoyer, Amanda R.; Johnson, Chad; Hoyer, Matthew R; Kernien, John F.; Nett, Jeniel E.

doi:10.1128/aac.00797-18

Cited by 14 publications

(20 citation statements)

References 23 publications

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“…Activation of NETosis in contact with fungal biofilm exposing eRNA/eDNA in ECM could also be supported by the antifungal treatment, such as with echinocandins. By influencing the fungal cell organization, it can augment the innate immune response of the host ( Hoyer et al., 2018 ). A better understanding of fungal biofilm formation, composition and stability during infection progression will open new avenues for the development of effective antifungal therapies.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Nucleic Acids Present in the Candida albicans Biofilm Trigger the Release of Neutrophil Extracellular Traps

Smolarz

Zawrotniak

Satała

et al. 2021

Front. Cell. Infect. Microbiol.

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Neutrophils, the first line of the host’s defense, use a variety of antimicrobial mechanisms to fight invading pathogens. One of the most crucial is the production of neutrophil extracellular traps (NETs) in the process called NETosis. The unique structure of NETs effectively inhibits the spread of pathogens and ensures their exposure to a high concentration of NET-embedded antimicrobial compounds. NETosis strategy is often used by the host to defend against fungal infection caused by Candida albicans. In immunocompromised patients, this microorganism is responsible for developing systemic fungal infections (candidiasis). This is correlated with the use of a vast array of virulence factors, leading to the acquisition of specific resistance to host defense factors and available drug therapies. One of the most important features favoring the development of drug resistance is a C. albicans ability to form biofilms that protect fungal cells mainly through the production of an extracellular matrix (ECM). Among the main ECM-building macromolecules extracellular nucleic acids have been identified and their role is probably associated with the stbilization of the biofilm structure. The complex interactions of immune cells with the thick ECM layer, comprising the first line of contact between these cells and the biofilm structure, are still poorly understood. Therefore, the current studies aimed to assess the release of extracellular nucleic acids by C. albicans strains at different stages of biofilm formation, and to determine the role of these molecules in triggering the NETosis. We showed for the first time that fungal nucleic acids, purified directly from mature C. albicans biofilm structure or obtained from the whole fungal cells, have the potential to induce NET release in vitro. In this study, we considered the involvement of TLR8 and TLR9 in NETosis activation. We showed that DNA and RNA molecules initiated the production of reactive oxygen species (ROS) by activation of the NADPH oxidase complex, essential for ROS-dependent NETosis. Furthermore, analysis of the cell migration showed that the nucleic acids located in the extracellular space surrounding the biofilm may be also effective chemotactic factors, driving the dynamic migration of human neutrophils to the site of ongoing fungal infection.

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Section: Discussionmentioning

confidence: 99%

Extracellular Nucleic Acids Present in the Candida albicans Biofilm Trigger the Release of Neutrophil Extracellular Traps

Smolarz

Zawrotniak

Satała

et al. 2021

Front. Cell. Infect. Microbiol.

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“…The fungal components involved in triggering this response are not certain. The finding that neutrophils are also activated by biofilms following treatment with echinocandin drugs, which unmask β-1,3 glucan, suggests a role for this polysaccharide (Katragkou et al, 2010;Hoyer et al, 2018;Simitsopoulou et al, 2018).…”

Section: Role Of Candida Biofilm Matrix In Immunitymentioning

confidence: 99%

“…may vary in morphology and density, the structures uniformly contain a polymeric extracellular matrix that encases and protects the fungal cells. The components of the extracellular matrix differ from those found in the Candida cell wall, and these moieties are proposed to modulate host recognition by concealing the cell wall components that typically interact with the immune system (Johnson et al, 2016;Zawrotniak et al, 2017;Hoyer et al, 2018). In addition, cells dispersed from biofilms exhibit characteristics distinct from cells growing under non-biofilm conditions (Sellam et al, 2009;Uppuluri et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

How Biofilm Growth Affects Candida-Host Interactions

Eix

Nett

2020

Front. Microbiol.

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Candida spp. proliferate as surface-associated biofilms in a variety of clinical niches. These biofilms can be extremely difficult to eradicate in healthcare settings. Cells within biofilm communities grow as aggregates and produce a protective extracellular matrix, properties that impact the ability of the host to respond to infection. Cells that disperse from biofilms display a phenotype of enhanced pathogenicity. In this review, we highlight host-biofilm interactions for Candida, focusing on how biofilm formation influences innate immune responses.

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“…In addition, Hoyer et al. ( 56 ) reported that C. albicans biofilms treated with appropriate concentrations of echinocandin unexpectedly stimulated the formation of NETs. In summary, although some elements of biofilms were found to trigger NET formation, the inhibitory action exhibited by biofilms as a whole has been confirmed.…”

Section: Multiple Virulence Factors Of C Albicans ...mentioning

confidence: 99%

Neutrophil Extracellular Traps in Candida albicans Infection

Liu

Chen

et al. 2022

Front. Immunol.

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Candida albicans is the most common pathogen causing clinical Candida infections. Neutrophils are a key member of the host innate immunity that plays an essential role in clearing invading C. albicans. In addition to the well-known defensive approaches such as phagocytosis, degranulation, and reactive oxygen species production, the formation of neutrophil extracellular traps (NETs) has also become an important way for neutrophils to defend against various pathogens. C. albicans has been reported to be capable of activating neutrophils to release NETs that subsequently kill fungi. The induction of NETs is affected by both the morphology and virulence factors of C. albicans, which also develops specific strategies to respond to the attack by NETs. Our review specifically focuses on the mechanisms by which C. albicans triggers NET formation and their subsequent interactions, which might provide meaningful insight into the innate immunity against C. albicans infection.

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Echinocandin Treatment of Candida albicans Biofilms Enhances Neutrophil Extracellular Trap Formation

Cited by 14 publications

References 23 publications

Extracellular Nucleic Acids Present in the Candida albicans Biofilm Trigger the Release of Neutrophil Extracellular Traps

Extracellular Nucleic Acids Present in the Candida albicans Biofilm Trigger the Release of Neutrophil Extracellular Traps

How Biofilm Growth Affects Candida-Host Interactions

Neutrophil Extracellular Traps in Candida albicans Infection

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