<i>Candida albicans</i> morphology: still in focus

Jacobsen, Ilse D.; Hube, Bernhard

doi:10.1080/14787210.2017.1290524

Cited by 33 publications

(27 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Candida albicans polymorphism is one of the most widely recognized attributes of this important human fungal pathogen ( Lu et al, 2014 ; Jacobsen and Hube, 2017 ; Noble et al, 2017 ). The most well studied morphologies are yeast and hyphae and the yeast to hypha dimorphic transition is thought to be a key virulence factor.…”

Section: Discussionmentioning

confidence: 99%

Zinc Limitation Induces a Hyper-Adherent Goliath Phenotype in Candida albicans

et al. 2017

Self Cite

View full text Add to dashboard Cite

Pathogenic microorganisms often face acute micronutrient limitation during infection due to the action of host-mediated nutritional immunity. The human fungal pathogen Candida albicans is polymorphic and its morphological plasticity is one of its most widely recognized pathogenicity attributes. Here we investigated the effect of zinc, iron, manganese, and copper limitation on C. albicans morphology. Restriction of zinc specifically resulted in the formation of enlarged, spherical yeasts, a phenotype which we term Goliath cells. This cellular response to zinc restriction was conserved in C. albicans, C. dubliniensis and C. tropicalis, but not in C. parapsilosis, C. lusitaniae or Debaryomyces hansenii, suggesting that it may have emerged in the last common ancestor of these related pathogenic species. Cell wall analysis revealed proportionally more chitin exposure on the Goliath cell surface. Importantly, these cells were hyper-adherent, suggesting a possible role in pathogenicity. Interestingly, the zincophore-encoding gene PRA1 was expressed by Goliath cells in zinc limited media and lack of Pra1 inhibited both cellular enlargement and adhesion. Goliath cells represent a further layer of Candida phenotypic plasticity.

show abstract

Section: Discussionmentioning

confidence: 99%

Zinc Limitation Induces a Hyper-Adherent Goliath Phenotype in Candida albicans

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…[ 4 ] and thus, a lot of effort has been devoted to combat C.a. [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…In fact, among the numerous factors which contribute to the pathogenicity of C.a. , the mostly studied ones, which are also recognised as the most critical ones, are the following two: (i) the adherence of yeast-form cells to a surface and (ii) the ability to switch between yeast and hyphal growth forms (dimorphism) [ 10 , 17 ]. Therefore, there is an urgent need for the development of materials that would ideally simultaneously affect both attached to the surface (sessile) and free-floating (planktonic) C.a.…”

Section: Introductionmentioning

confidence: 99%

Fungicidal PMMA-Undecylenic Acid Composites

Petrović

Bonvin

Hofmann

et al. 2018

IJMS

View full text Add to dashboard Cite

Undecylenic acid (UA), known as antifungal agent, still cannot be used to efficiently modify commercial dental materials in such a way that this affects Candida. Actually, issues with Candida infections and fungal resistance compromise the use of Poly(methyl-methacrylate) (PMMA) as dental material. The challenge remains to turn PMMA into an antifugal material, which can ideally affect both sessile (attached) and planktonic (free-floating) Candida cells. We aimed to tackle this challenge by designing PMMA-UA composites with different UA concentrations (3-12%). We studied their physico-chemical properties, the antifungal effect on Candida and the cytotoxicity toward human cells. We found that UA changes the PMMA surface into a more hydrophilic one. Mainly, as-preparation composites with ≥6% UA reduced sessile Candida for >90%. After six days, the composites were still efficiently reducing the sessile Candida cells (for~70% for composites with ≥6% UA). Similar results were recorded for planktonic Candida. Moreover, the inhibition zone increased along with the UA concentration. The antifungal effect of UA was also examined at the surface of an UA-loaded agar and the minimal inhibitory concentration (MIC90) was below the lowest-studied 0.0125% UA. Furthermore, the embedded filamentation test after 24 h and 48 h showed complete inhibition of the Candida growth at 0.4% UA.

show abstract

“…The capacity for invasive hyphal growth is important for pathogenicity of C. albicans , due to roles such as tissue invasion and evasion of innate immune responses (Sudbery, 2011 ; Jacobsen and Hube, 2017 ). Hyphal growth of the gem1 Δ / Δ mutant was drastically reduced on mannitol-containing solid Spider media (Figure 5A ).…”

Section: Resultsmentioning

confidence: 99%

The Mitochondrial GTPase Gem1 Contributes to the Cell Wall Stress Response and Invasive Growth of Candida albicans

Koch

Tucey

et al. 2017

Front. Microbiol.

View full text Add to dashboard Cite

The interactions of mitochondria with the endoplasmic reticulum (ER) are crucial for maintaining proper mitochondrial morphology, function and dynamics. This enables cells to utilize their mitochondria optimally for energy production and anabolism, and it further provides for metabolic control over developmental decisions. In fungi, a key mechanism by which ER and mitochondria interact is via a membrane tether, the protein complex ERMES (ER-Mitochondria Encounter Structure). In the model yeast Saccharomyces cerevisiae, the mitochondrial GTPase Gem1 interacts with ERMES, and it has been proposed to regulate its activity. Here we report on the first characterization of Gem1 in a human fungal pathogen. We show that in Candida albicans Gem1 has a dominant role in ensuring proper mitochondrial morphology, and our data is consistent with Gem1 working with ERMES in this role. Mitochondrial respiration and steady state cellular phospholipid homeostasis are not impacted by inactivation of GEM1 in C. albicans. There are two major virulence-related consequences of disrupting mitochondrial morphology by GEM1 inactivation: C. albicans becomes hypersusceptible to cell wall stress, and is unable to grow invasively. In the gem1Δ/Δ mutant, it is specifically the invasive capacity of hyphae that is compromised, not the ability to transition from yeast to hyphal morphology, and this phenotype is shared with ERMES mutants. As a consequence of the hyphal invasion defect, the gem1Δ/Δ mutant is drastically hypovirulent in the worm infection model. Activation of the mitogen activated protein (MAP) kinase Cek1 is reduced in the gem1Δ/Δ mutant, and this function could explain both the susceptibility to cell wall stress and lack of invasive growth. This result establishes a new, respiration-independent mechanism of mitochondrial control over stress signaling and hyphal functions in C. albicans. We propose that ER-mitochondria interactions and the ER-Mitochondria Organizing Network (ERMIONE) play important roles in adaptive responses in fungi, in particular cell surface-related mechanisms that drive invasive growth and stress responsive behaviors that support fungal pathogenicity.

show abstract

Candida albicans morphology: still in focus

Cited by 33 publications

References 69 publications

Zinc Limitation Induces a Hyper-Adherent Goliath Phenotype in Candida albicans

Zinc Limitation Induces a Hyper-Adherent Goliath Phenotype in Candida albicans

Fungicidal PMMA-Undecylenic Acid Composites

The Mitochondrial GTPase Gem1 Contributes to the Cell Wall Stress Response and Invasive Growth of Candida albicans

Contact Info

Product

Resources

About