Candida albicans Hyphal Expansion Causes Phagosomal Membrane Damage and Luminal Alkalinization

Westman, Johannes; Moran, Gary P.; Mogavero, Selene; Hube, Bernhard; Grinstein, Sergio

doi:10.1128/mbio.01226-18

Cited by 95 publications

(76 citation statements)

References 54 publications

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“…The mature phagosome is acidic and nutrient deprived, which either completely inhibits or partly delays yeast‐to‐hypha transition (Slesiona et al, ). In vitro, C. albicans proliferation is delayed but not completely inhibited within the phagosome, and in most experimental setting, hyphal formation is induced after phagocytosis by macrophages (but not neutrophils; Fernandez‐Arenas et al, ; Fradin et al, ; Rubin‐Bejerano, Fraser, Grisafi, & Fink, ; Westman, Moran, Mogavero, Hube, & Grinstein, ).…”

Section: Membrane Distension and Disruption By Mechanical Forces Genementioning

confidence: 99%

“…This, in turn, causes membrane distension followed by rupture and pathogen escape (Figure b; Seider, Heyken, Luttich, Miramon, & Hube, ; Wartenberg et al, ; Westman et al, ). In vitro, approximately 4 hr of postphagocytosis of an individual surviving C. albicans cell, the phagosomal membrane is stretched to the point where it ruptures, resulting in phagosomal alkalization (Westman et al, ). The rupture likely causes a release of phagosomal contents, including secreted fungal proteins and host proteases (i.e., cathepsins; Figure b).…”

Section: Membrane Distension and Disruption By Mechanical Forces Genementioning

confidence: 99%

“…The rupture likely causes a release of phagosomal contents, including secreted fungal proteins and host proteases (i.e., cathepsins; Figure b). To highlight the importance of the mechanical stress and disruption, the authors demonstrated that “yeast‐locked” mutant cells remain trapped within the phagosome (Wartenberg et al, ; Westman et al, ).…”

Section: Membrane Distension and Disruption By Mechanical Forces Genementioning

confidence: 99%

“…After intraphagosomal yeast‐to‐hypha transition, the expanding C. albicans distends the phagosomal membrane (Westman et al, ). Although phagosomal rupture is mainly a result of the hyphal expansion, an ECE1 ‐deficient strain alkalinized the phagosomal lumen at a slower rate (Westman et al, ). This suggests a supporting role for candidalysin in phagosomal membrane permeabilization (Figure b).…”

Section: Candidalysin the First Pore‐forming Toxin Identified In Thementioning

confidence: 99%

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Integrity under stress: Host membrane remodelling and damage by fungal pathogens

Westman

Hube

Fairn

2019

Cellular Microbiology

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Membrane bilayers of eukaryotic cells are an amalgam of lipids and proteins that distinguish organelles and compartmentalise cellular functions. The mammalian cell has evolved mechanisms to sense membrane tension or damage and respond as needed. In the case of the plasma membrane and phagosomal membrane, these bilayers act as a barrier to microorganisms and are a conduit by which the host interacts with pathogens, including fungi such as Candida, Cryptococcus, Aspergillus, or Histoplasma species. Due to their size, morphological flexibility, ability to produce long filaments, secrete pathogenicity factors, and their potential to replicate within the phagosome, fungi can assault host membranes in a variety of physical and biochemical ways. In addition, the recent discovery of a fungal pore‐forming peptide toxin further highlights the importance of membrane biology in the outcomes between host and fungal cells. In this review, we discuss the apparent “stretching” of membranes as a sophisticated biological response and the role of vesicular transport in combating membrane stress and damage. We also review the known pathogenicity factors and physical properties of fungal pathogens in the context of host membranes and discuss how this may contribute to pathogenic interactions between fungal and host cells.

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Section: Membrane Distension and Disruption By Mechanical Forces Genementioning

confidence: 99%

Section: Membrane Distension and Disruption By Mechanical Forces Genementioning

confidence: 99%

Section: Membrane Distension and Disruption By Mechanical Forces Genementioning

confidence: 99%

Section: Candidalysin the First Pore‐forming Toxin Identified In Thementioning

confidence: 99%

See 2 more Smart Citations

Integrity under stress: Host membrane remodelling and damage by fungal pathogens

Westman

Hube

Fairn

2019

Cellular Microbiology

Self Cite

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“…While macrophages also efficiently phagocytize Candida, their killing ability is lower than that of neutrophils, leading to the smaller contribution of macrophages during C. albicans infections (Cheng et al, 2012). Moreover, the fungus can induce macrophage cell death by hypha-mediated membrane piercing (Vylkova and Lorenz, 2014;Westman et al, 2018) or activation of NLRP3-dependent pyroptosis (Uwamahoro et al, 2014;Wellington et al, 2014;Vylkova and Lorenz, 2017). The pyroptotic process seems to be independent from candidalysin, although the toxin is responsible for the activation of NLRP3 inflammasome and caspase-1 in macrophages and dendritic cells (Kasper et al, 2018;Rogiers et al, 2019).…”

Section: Anti-candida Innate Immunity At the Mucosamentioning

confidence: 99%

New Insights in Candida albicans Innate Immunity at the Mucosa: Toxins, Epithelium, Metabolism, and Beyond

Pellón

Nasab

Moyes

2020

Front. Cell. Infect. Microbiol.

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Spiked Nanostructures Disrupt Fungal Biofilm and Impart Increased Sensitivity to Antifungal Treatment

Hayles

Bright

Wood

et al. 2022

Adv Materials Inter

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The superiority of titanium as a biomaterial is reflected in its corrosion resistance, mechanical strength, biocompatibility, and osseointegration capabilities. [1a] Although there is a high success rate associated with implanted devices, failure is not uncommon. One of the primary causes of implant failure is implantassociated infections (IAI). [2] In the field of orthopaedics, approximately 1-2% of joint replacement arthroplasties result in IAI. [3] The IAI rate is significantly higher in the periodontal field, with peri-implantitis seen in as many as 1 in 3 patients. [4] Infections involving fungal pathogens are emerging in both of these clinical fields, and Candida species are detected in as many as 90% of fungal IAI cases. [5] Candida albicans represents the most common fungal threat, but other notable species include Candida parapsilosis, Candida tropicalis, and Candida glabrata. [5d] In polymicrobial biofilms, C. albicans can protect Porphyromonas gingivalis from adverse conditions [6] and promote drug resistance in Staphylococcus aureus. [7] Its common occurrence in IAI can be attributed to the fact that C. albicans is found amongst the normal skin microbiota as a commensal microbe, and can occasionally translocate from the skin to the implanted device during surgery. [8] In a subset of the population, such as diabetics or those who have an otherwise compromised immune system, C. albicans can switch from its normal commensal state to an opportunistic pathogen. This is of particular concern because once a fungal infection becomes systemic, it is associated with a mortality rate of up to 50%. [9] In systemic candidiasis, the kidney is one of the primary organs to be affected, commonly leading to renal failure. [10] As a fungal pathogen, the virulence mechanisms of C. albicans differ from bacterial pathogens. One striking difference is the ability of pathogenic fungi to reversibly switch between two alternate phenotypes-an ovoid-shaped yeast phenotype and a filamentous hyphal phenotype, and this process is referred to as morphogenesis. [11] The yeast phenotype is associated with initial surface colonization, and later dissemination. The hyphal phenotype acts as structural support and promotes tissue invasion. [12] Invasion of host tissue allows C. albicans to enter the bloodstream and translocate around the body. Within the bloodstream, the presence of serum and the slightly alkaline pH provides ideal conditions for hyphal cell growth, which then allows the pathogen to invade There is a globally increasing demand for medically implanted devices, partly spurred by an aging population. In parallel, there is a proportionate increase in implant associated infection. Much focus has been directed toward the development of techniques to fabricate nanostructured antimicrobial biomaterials to mitigate infection. The present study investigates the interaction of the fungal pathogen Candida albicans with an antimicrobial surface bearing nanoscale protrusions. C. albicans cells were observed to be affected by cell ...

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Candida albicans Hyphal Expansion Causes Phagosomal Membrane Damage and Luminal Alkalinization

Cited by 95 publications

References 54 publications

Integrity under stress: Host membrane remodelling and damage by fungal pathogens

Integrity under stress: Host membrane remodelling and damage by fungal pathogens

New Insights in Candida albicans Innate Immunity at the Mucosa: Toxins, Epithelium, Metabolism, and Beyond

Spiked Nanostructures Disrupt Fungal Biofilm and Impart Increased Sensitivity to Antifungal Treatment

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