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Candida albicans Virulence Factors and Its Pathogenecity
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Candida albicans Virulence Factors and Its Pathogenecity

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (31 May 2020) | Viewed by 75690

Special Issue Editors

Prof. Dr. Mariana Henriques

E-Mail Website
Guest Editor
Department of Biological Engineering, University of Minho, 4715-338 Braga, Portugal
Interests: Non-Candida albicans Candida species; virulence factors; biofilms; antifungal resistance; natural antimicrobial agents; host interaction; biomaterials
Special Issues, Collections and Topics in MDPI journals
Dr. Sónia Silva

E-Mail Website
Guest Editor
1. I.P – National Institute for Agrarian and Veterinarian Research (INIAV), Vairão, Portugal
2. Centre of Biological Engineering (CEB), Laboratory of Research in Biofilms Rosário Oliveira (LIBRO), Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal
3. LABBELS–Associate Laboratory, Braga/Guimarães, Portugal
Interests: food microbiology; pet animal infections; medical biotechnology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Candida albicans lives commensally on the skin and mucosal surfaces of genital, intestinal, vaginal, urinary and oral tracts of 80% of healthy individuals. An imbalance between the host immunity and this opportunistic fungus may trigger mucosal infections followed by dissemination via bloodstream and infection of internal organs. Candida albicans is considered the most common opportunistic pathogenic fungus in humans and a causative agent of 60% of mucosal infections and 40% of candidemia cases. Several virulence factors are known to be responsible for Candida infections, such as adherence to host surfaces, biofilm formation and secretion of hydrolytic enzymes. Moreover, Candida resistance to traditional antimicrobial agents, especially the ones from azole group, is well known, especially when Candida cells are in biofilm form.

The aim of this Special Issue is to gather more information on the important human pathogen, Candida albicans. We would like to invite researchers to submit their research or review articles on Candida albicans concerning different aspects, such as virulent factors, resistance to antimicrobial agents, new therapies, molecular pathways and host interactions.

Prof. Dr. Mariana Henriques
Dr. Sónia Carina Silva
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Candida albicans
  • virulence factors
  • antimicrobial resistance
  • host
  • molecular pathways

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Published Papers (15 papers)

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Editorial

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3 pages, 208 KiB  
Editorial
Candida Albicans Virulence Factors and Its Pathogenicity
by Mariana Henriques and Sónia Silva
Microorganisms 2021, 9(4), 704; https://doi.org/10.3390/microorganisms9040704 - 29 Mar 2021
Cited by 17 | Viewed by 2961
Abstract
Candida albicans lives as commensal on the skin and mucosal surfaces of the genital, intestinal, vaginal, urinary, and oral tracts of 80% of healthy individuals [...] Full article
(This article belongs to the Special Issue Candida albicans Virulence Factors and Its Pathogenecity)

Research

Jump to: Editorial, Review

16 pages, 3042 KiB  
Article
Longer Ubiquinone Side Chains Contribute to Enhanced Farnesol Resistance in Yeasts
by Ruvini U. Pathirana, Cory Boone and Kenneth W. Nickerson
Microorganisms 2020, 8(11), 1641; https://doi.org/10.3390/microorganisms8111641 - 23 Oct 2020
Cited by 6 | Viewed by 2163
Abstract
Ubiquinones (UQ) are intrinsic lipid components of many membranes. Besides their role in electron-transfer reactions there is evidence for them acting as free radical scavengers, yet their other roles in biological systems have received little study. The dimorphic fungal pathogen Candida albicans secretes [...] Read more.
Ubiquinones (UQ) are intrinsic lipid components of many membranes. Besides their role in electron-transfer reactions there is evidence for them acting as free radical scavengers, yet their other roles in biological systems have received little study. The dimorphic fungal pathogen Candida albicans secretes farnesol as both a virulence factor and a quorum-sensing molecule. Thus, we were intrigued by the presence of UQ9 isoprenologue in farnesol-producing Candida species while other members of this genera harbor UQ7 as their major electron carrier. We examined the effect of UQ side chain length in Saccharomyces cerevisiae and C. albicans with a view towards identifying the mechanisms by which C. albicans protects itself from the high levels of farnesol it secretes, levels that are toxic to many other fungi including S. cerevisiae. In this study, we identify UQ9 as the major UQ isoprenoid in C. albicans, regardless of growth conditions or cell morphology. A S. cerevisiae model yeast engineered to make UQ9 instead of UQ6 was 4–5 times more resistant to exogenous farnesol than the parent yeast and this resistance was accompanied by greatly reduced reactive oxygen species (ROS) production. The resistance provided by UQ9 is specific for farnesol in that it does not increase resistance to high salt (1M NaCl) or other oxidants (5 mM H2O2 or 1 mM menadione). Additionally, the protection provided by UQ9 appears to be structural rather than transcriptional; UQ9 does not alter key transcriptional responses to farnesol stress. Here, we propose a model in which the longer UQ side chains are more firmly embedded in the mitochondrial membrane making them harder to pry out, so that in the presence of farnesol they remain functional without producing excess ROS. C. albicans and Candida dubliniensis evolved to use UQ9 rather than UQ7 as in other Candida species or UQ6 as in S. cerevisiae. This adaptive mechanism highlights the significance of UQ side chains in farnesol production and resistance quite apart from being an electron carrier in the respiratory chain. Full article
(This article belongs to the Special Issue Candida albicans Virulence Factors and Its Pathogenecity)
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27 pages, 6847 KiB  
Article
Fungistatic Action of N-Acetylcysteine on Candida albicans Biofilms and Its Interaction with Antifungal Agents
by Thaís Soares Bezerra Santos Nunes, Leticia Matheus Rosa, Yuliana Vega-Chacón and Ewerton Garcia de Oliveira Mima
Microorganisms 2020, 8(7), 980; https://doi.org/10.3390/microorganisms8070980 - 30 Jun 2020
Cited by 11 | Viewed by 6250
Abstract
Therapies targeted to fungal biofilms, mainly against the matrix, and therapies that do not induce microbial resistance are relevant. N-acetylcysteine (NAC), a mucolytic agent, has shown antimicrobial action. This study evaluated the effect of NAC against fluconazole-susceptible (CaS) and -resistant (CaR) Candida albicans [...] Read more.
Therapies targeted to fungal biofilms, mainly against the matrix, and therapies that do not induce microbial resistance are relevant. N-acetylcysteine (NAC), a mucolytic agent, has shown antimicrobial action. This study evaluated the effect of NAC against fluconazole-susceptible (CaS) and -resistant (CaR) Candida albicans. The susceptibility of planktonic cultures to NAC, the effect of NAC on biofilms and their matrix, the interaction of NAC with antifungal agents, and confocal microscopy were evaluated. Data were analyzed descriptively and by the ANOVA/Welch and Tukey/Gomes–Howell tests. The minimum inhibitory concentration (MIC) of NAC was 25 mg/mL for both strains. NAC significantly reduced the viability of both fungal strains. Concentrations higher than the MIC (100 and 50 mg/mL) reduced the viability and the biomass. NAC at 12.5 mg/mL increased the fungal viability. NAC also reduced the soluble components of the biofilm matrix, and showed synergism with caspofungin against planktonic cultures of CaS, but not against biofilms. Confocal images demonstrated that NAC reduced the biofilm thickness and the fluorescence intensity of most fluorochromes used. High concentrations of NAC had similar fungistatic effects against both strains, while a low concentration showed the opposite result. The antibiofilm action of NAC was due to its fungistatic action. Full article
(This article belongs to the Special Issue Candida albicans Virulence Factors and Its Pathogenecity)
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Graphical abstract

12 pages, 1653 KiB  
Article
Known Antimicrobials Versus Nortriptyline in Candida albicans: Repositioning an Old Drug for New Targets
by Marina Caldara and Nelson Marmiroli
Microorganisms 2020, 8(5), 742; https://doi.org/10.3390/microorganisms8050742 - 15 May 2020
Cited by 5 | Viewed by 2282
Abstract
Candida albicans has the capacity to develop resistance to commonly used antimicrobials, and to solve this problem, drug repositioning and new drug combinations are being studied. Nortriptyline, a tricyclic antidepressant, was shown to have the capacity to inhibit biofilm and hyphae formation, along [...] Read more.
Candida albicans has the capacity to develop resistance to commonly used antimicrobials, and to solve this problem, drug repositioning and new drug combinations are being studied. Nortriptyline, a tricyclic antidepressant, was shown to have the capacity to inhibit biofilm and hyphae formation, along with the ability to efficiently kill cells in a mature biofilm. To use nortriptyline as a new antimicrobial, or in combination with known drugs to increase their actions, it is important to characterize in more detail the effects of this drug on the target species. In this study, the Candida albicans GRACE™ collection and a Haplo insufficiency profiling were employed to identify the potential targets of nortriptyline, and to classify, in a parallel screening with amphotericin B, caspofungin, and fluconazole, general multi-drug resistance genes. The results identified mutants that, during biofilm formation and upon treatment of a mature biofilm, are sensitive or tolerant to nortriptyline, or to general drug treatments. Gene ontology analysis recognized the categories of ribosome biogenesis and spliceosome as enriched upon treatment with the tricyclic antidepressant, while mutants in oxidative stress response and general stress response were commonly retrieved upon treatment with any other drug. The data presented suggest that nortriptyline can be considered a “new” antimicrobial drug with large potential for application to in vivo infection models. Full article
(This article belongs to the Special Issue Candida albicans Virulence Factors and Its Pathogenecity)
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14 pages, 3340 KiB  
Article
Evaluation of Biofilm Formation in Candida tropicalis Using a Silicone-Based Platform with Synthetic Urine Medium
by Yi-Kai Tseng, Yu-Chia Chen, Chien-Jui Hou, Fu-Sheng Deng, Shen-Huan Liang, Sin Yong Hoo, Chih-Chieh Hsu, Cai-Ling Ke and Ching-Hsuan Lin
Microorganisms 2020, 8(5), 660; https://doi.org/10.3390/microorganisms8050660 - 01 May 2020
Cited by 13 | Viewed by 2793
Abstract
Molecular mechanisms of biofilm formation in Candida tropicalis and current methods for biofilm analyses in this fungal pathogen are limited. (2) Methods: Biofilm biomass and crystal violet staining of the wild-type and each gene mutant strain of C. tropicalis were evaluated on silicone [...] Read more.
Molecular mechanisms of biofilm formation in Candida tropicalis and current methods for biofilm analyses in this fungal pathogen are limited. (2) Methods: Biofilm biomass and crystal violet staining of the wild-type and each gene mutant strain of C. tropicalis were evaluated on silicone under synthetic urine culture conditions. (3) Results: Seven media were tested to compare the effects on biofilm growth with or without silicone. Results showed that biofilm cells of C. tropicalis were unable to form firm biofilms on the bottom of 12-well polystyrene plates. However, on a silicone-based platform, Roswell Park Memorial Institute 1640 (RPMI 1640), yeast nitrogen base (YNB) + 1% glucose, and synthetic urine media were able to induce strong biofilm growth. In particular, replacement of Spider medium with synthetic urine in the adherence step and the developmental stage is necessary to gain remarkably increased biofilms. Interestingly, unlike Candida albicans, the C. tropicalis ROB1 deletion strain but not the other five biofilm-associated mutants did not cause a significant reduction in biofilm formation, suggesting that the biofilm regulatory circuits of the two species are divergent. (4) Conclusions: This system for C. tropicalis biofilm analyses will become a useful tool to unveil the biofilm regulatory network in C. tropicalis. Full article
(This article belongs to the Special Issue Candida albicans Virulence Factors and Its Pathogenecity)
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11 pages, 1682 KiB  
Article
Candida albicans Adaptation on Simulated Human Body Fluids under Different pH
by Ana Barbosa, Daniela Araújo, Eduarda Ribeiro, Mariana Henriques and Sónia Silva
Microorganisms 2020, 8(4), 511; https://doi.org/10.3390/microorganisms8040511 - 03 Apr 2020
Cited by 11 | Viewed by 3445
Abstract
Candida albicans remains the most problematic of all Candida species, causing severe infections. Adaptation to different human body niches, such oral and urinary tracts, has been shown to be essential for survival and critical for virulence of C. albicans. Thus, the present work [...] Read more.
Candida albicans remains the most problematic of all Candida species, causing severe infections. Adaptation to different human body niches, such oral and urinary tracts, has been shown to be essential for survival and critical for virulence of C. albicans. Thus, the present work aimed to study the behaviour of C. albicans on simulated human body fluids (artificial saliva and urine) at different values of pH (pH 5.8 and 7) by determining its ability to develop two of the most important virulence factors: biofilms and filamentous forms. Under this study, it was demonstrated that C. albicans was able to grow as free cells and to develop biofilm communities composed of multiple cell types (yeast and elongated hyphal cells) on both simulated human body fluids and under different pH. It was interesting to note that the pH had little impact on C. albicans planktonic and biofilm growth, despite influencing the development of filamentous shapes in artificial saliva and urine. So, it was possible to infer that C. albicans presents a high plasticity and adaptability to different human body fluids, namely saliva and urine. These can be the justification for the high number of oral and urinary candidiasis in the whole world. Full article
(This article belongs to the Special Issue Candida albicans Virulence Factors and Its Pathogenecity)
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12 pages, 1550 KiB  
Article
Cooperative Role of MAPK Pathways in the Interaction of Candida albicans with the Host Epithelium
by Inês Correia, Daniel Prieto, Elvira Román, Duncan Wilson, Bernhard Hube, Rebeca Alonso-Monge and Jesús Pla
Microorganisms 2020, 8(1), 48; https://doi.org/10.3390/microorganisms8010048 - 25 Dec 2019
Cited by 15 | Viewed by 3283
Abstract
Candida albicans is an important human fungal pathogen responsible for tens of millions of infections as well as hundreds of thousands of severe life-threatening infections each year. MAP kinase (MAPK) signal transduction pathways facilitate the sensing and adaptation to external stimuli and control [...] Read more.
Candida albicans is an important human fungal pathogen responsible for tens of millions of infections as well as hundreds of thousands of severe life-threatening infections each year. MAP kinase (MAPK) signal transduction pathways facilitate the sensing and adaptation to external stimuli and control the expression of key virulence factors such as the yeast-to-hypha transition, the biogenesis of the cell wall, and the interaction with the host. In the present study, we have combined molecular approaches and infection biology to analyse the role of C. albicans MAPK pathways during an epithelial invasion. Hog1 was found to be important for adhesion to abiotic surfaces but was dispensable for damage to epithelial cells. The Mkc1 cell wall integrity (CWI) and Cek1 pathways, on the other hand, were both required for oral epithelial damage. Analysis of the ability to penetrate nutrient-rich semi-solid media revealed a cooperative role for Cek1 and Mkc1 in this process. Finally, cek2Δ (as well as cek1Δ) but not mkc1Δ or hog1Δ mutants, exhibited elevated β-glucan unmasking as revealed by immunofluorescence studies. Therefore, the four MAPK pathways play distinct roles in adhesion, epithelial damage, invasion and cell wall remodelling that may contribute to the pathogenicity of C. albicans. Full article
(This article belongs to the Special Issue Candida albicans Virulence Factors and Its Pathogenecity)
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17 pages, 4017 KiB  
Article
A Crucial Role for Ergosterol in Plasma Membrane Composition, Localisation, and Activity of Cdr1p and H+-ATPase in Candida albicans
by Jakub Suchodolski, Jakub Muraszko, Przemysław Bernat and Anna Krasowska
Microorganisms 2019, 7(10), 378; https://doi.org/10.3390/microorganisms7100378 - 22 Sep 2019
Cited by 32 | Viewed by 5006
Abstract
Candida albicans is an opportunistic fungal pathogen of humans. Treatment of C. albicans infections relies on azoles, which target the lanosterol 14α-demethylase (Erg11p) encoded by the ERG11 gene. Our results show that targeted gene disruption of ERG11 can result in resistance to ergosterol-dependent [...] Read more.
Candida albicans is an opportunistic fungal pathogen of humans. Treatment of C. albicans infections relies on azoles, which target the lanosterol 14α-demethylase (Erg11p) encoded by the ERG11 gene. Our results show that targeted gene disruption of ERG11 can result in resistance to ergosterol-dependent drugs (azoles and amphotericin B), auxotrophy and aerobically viable erg11Δ/Δ cells. Abnormal sterol deposition and lack of ergosterol in the erg11Δ/Δ strain leads to reduced plasma membrane (PM) fluidity, as well as dysfunction of the vacuolar and mitochondrial membranes, resulting respectively in defects in vacuole fusion and a reduced intracellular ATP level. The altered PM structure of the erg11Δ/Δ strain contributes to delocalisation of H+-ATPase and the Cdr1 efflux pump from the PM to vacuoles and, resulting in a decrease in PM potential (Δψ) and increased sensitivity to ergosterol-independent xenobiotics. This new insight into intracellular processes under Erg11p inhibition may lead to a better understanding of the indirect effects of azoles on C. albicans cells and the development of new treatment strategies for resistant infections. Full article
(This article belongs to the Special Issue Candida albicans Virulence Factors and Its Pathogenecity)
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12 pages, 2091 KiB  
Article
Plasma Membrane Potential of Candida albicans Measured by Di-4-ANEPPS Fluorescence Depends on Growth Phase and Regulatory Factors
by Jakub Suchodolski and Anna Krasowska
Microorganisms 2019, 7(4), 110; https://doi.org/10.3390/microorganisms7040110 - 24 Apr 2019
Cited by 15 | Viewed by 4262
Abstract
The potential of the plasma membrane (Δψ) regulates the electrochemical potential between the outer and inner sides of cell membranes. The opportunistic fungal pathogen, Candida albicans, regulates the membrane potential in response to environmental conditions, as well as the physiological state of the [...] Read more.
The potential of the plasma membrane (Δψ) regulates the electrochemical potential between the outer and inner sides of cell membranes. The opportunistic fungal pathogen, Candida albicans, regulates the membrane potential in response to environmental conditions, as well as the physiological state of the cell. Here we demonstrate a new method for detection of cell membrane depolarization/permeabilization in C. albicans using the potentiometric zwitterionic dye di-4-ANEPPS. Di-4-ANEPPS measures the changes in the cell Δψ depending on the phases of growth and external factors regulating Δψ, such as potassium or calcium chlorides, amiodarone or DM-11 (inhibitor of H+-ATPase). We also demonstrated that di-4-ANEPPS is a good tool for fast measurement of the influence of amphipathic compounds on Δψ. Full article
(This article belongs to the Special Issue Candida albicans Virulence Factors and Its Pathogenecity)
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Review

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18 pages, 1857 KiB  
Review
Candida albicans Virulence Factors and Pathogenicity for Endodontic Infections
by Yeon-Jee Yoo, A Reum Kim, Hiran Perinpanayagam, Seung Hyun Han and Kee-Yeon Kum
Microorganisms 2020, 8(9), 1300; https://doi.org/10.3390/microorganisms8091300 - 26 Aug 2020
Cited by 34 | Viewed by 6572
Abstract
Candida albicans (C. albicans) is the fungus most frequently isolated from endodontic root canal infections. Although recognized by dental pulp and periradicular tissue cells that elicit immune responses, it eludes host defenses and elicits cell death. Then, C. albicans binds tooth [...] Read more.
Candida albicans (C. albicans) is the fungus most frequently isolated from endodontic root canal infections. Although recognized by dental pulp and periradicular tissue cells that elicit immune responses, it eludes host defenses and elicits cell death. Then, C. albicans binds tooth dentin, forms biofilms, and invades dentinal tubules to resist intracanal disinfectants and endodontic treatments. Insensitive to most common medicaments, it survives sequestered within biofilms and intratubular dentin. Thus, C. albicans has been associated with cases of persistent or refractory root canal infections. Its treatment strategies may require alternative intracanal irrigants, intracanal medicaments such as chlorhexidine gel or human beta defensin-3 (HBD3), Ca-Si-based obturating materials, and microsurgical procedures. Full article
(This article belongs to the Special Issue Candida albicans Virulence Factors and Its Pathogenecity)
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25 pages, 980 KiB  
Review
Moonlighting Proteins at the Candidal Cell Surface
by Dorota Satala, Justyna Karkowska-Kuleta, Aleksandra Zelazna, Maria Rapala-Kozik and Andrzej Kozik
Microorganisms 2020, 8(7), 1046; https://doi.org/10.3390/microorganisms8071046 - 14 Jul 2020
Cited by 46 | Viewed by 4215
Abstract
The cell wall in Candida albicans is not only a tight protective envelope but also a point of contact with the human host that provides a dynamic response to the constantly changing environment in infection niches. Particularly important roles are attributed to proteins [...] Read more.
The cell wall in Candida albicans is not only a tight protective envelope but also a point of contact with the human host that provides a dynamic response to the constantly changing environment in infection niches. Particularly important roles are attributed to proteins exposed at the fungal cell surface. These include proteins that are stably and covalently bound to the cell wall or cell membrane and those that are more loosely attached. Interestingly in this regard, numerous loosely attached proteins belong to the class of “moonlighting proteins” that are originally intracellular and that perform essentially different functions in addition to their primary housekeeping roles. These proteins also demonstrate unpredicted interactions with non-canonical partners at an a priori unexpected extracellular location, achieved via non-classical secretion routes. Acting both individually and collectively, the moonlighting proteins contribute to candidal virulence and pathogenicity through their involvement in mechanisms critical for successful host colonization and infection, such as the adhesion to host cells, interactions with plasma homeostatic proteolytic cascades, responses to stress conditions and molecular mimicry. The documented knowledge of the roles of these proteins in C. albicans pathogenicity has utility for assisting the design of new therapeutic, diagnostic and preventive strategies against candidiasis. Full article
(This article belongs to the Special Issue Candida albicans Virulence Factors and Its Pathogenecity)
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17 pages, 355 KiB  
Review
Bio- and Nanotechnology as the Key for Clinical Application of Salivary Peptide Histatin: A Necessary Advance
by Carolina Reis Zambom, Fauller Henrique da Fonseca and Saulo Santesso Garrido
Microorganisms 2020, 8(7), 1024; https://doi.org/10.3390/microorganisms8071024 - 10 Jul 2020
Cited by 6 | Viewed by 2498
Abstract
Candida albicans is a common microorganism of human’s microbiota and can be easily found in both respiratory and gastrointestinal tracts as well as in the genitourinary tract. Approximately 30% of people will be infected by C. albicans during their lifetime. Due to its [...] Read more.
Candida albicans is a common microorganism of human’s microbiota and can be easily found in both respiratory and gastrointestinal tracts as well as in the genitourinary tract. Approximately 30% of people will be infected by C. albicans during their lifetime. Due to its easy adaptation, this microorganism started to present high resistance to antifungal agents which is associated with their indiscriminate use. There are several reports of adaptive mechanisms that this species can present. Some of them are intrinsic alteration in drug targets, secretion of extracellular enzymes to promote host protein degradation and efflux receptors that lead to a diminished action of common antifungal and host’s innate immune response. The current review aims to bring promising alternatives for the treatment of candidiasis caused mainly by C. albicans. One of these alternatives is the use of antifungal peptides (AFPs) from the Histatin family, like histatin-5. Besides that, our focus is to show how nanotechnology can allow the application of these peptides for treatment of this microorganism. In addition, our intention is to show the importance of nanoparticles (NPs) for this purpose, which may be essential in the near future. Full article
(This article belongs to the Special Issue Candida albicans Virulence Factors and Its Pathogenecity)
17 pages, 289 KiB  
Review
Candida and Candidiasis—Opportunism Versus Pathogenicity: A Review of the Virulence Traits
by Cristina Nicoleta Ciurea, Irina-Bianca Kosovski, Anca Delia Mare, Felicia Toma, Ionela Anca Pintea-Simon and Adrian Man
Microorganisms 2020, 8(6), 857; https://doi.org/10.3390/microorganisms8060857 - 06 Jun 2020
Cited by 80 | Viewed by 7100
Abstract
One of the most important questions in microbiology nowadays, is how apparently harmless, commensal yeasts like Candida spp. can cause a rising number of infections. The occurrence of the disease requires firstly the attachment to the host cells, followed by the invasion of [...] Read more.
One of the most important questions in microbiology nowadays, is how apparently harmless, commensal yeasts like Candida spp. can cause a rising number of infections. The occurrence of the disease requires firstly the attachment to the host cells, followed by the invasion of the tissue. The adaptability translates into a rapid ability to respond to stress factors, to take up nutrients or to multiply under different conditions. By forming complex intracellular networks such as biofilms, Candida spp. become not only more refractive to antifungal therapies but also more prone to cause disease. The inter-microbial interactions can enhance the virulence of a strain. In vivo, the fungal cells face a multitude of challenges and, as a result, they develop complex strategies serving one ultimate goal: survival. This review presents the virulence factors of the most important Candida spp., contributing to a better understanding of the onset of candidiasis and raising awareness of the highly complex interspecies interactions that can change the outcome of the disease. Full article
(This article belongs to the Special Issue Candida albicans Virulence Factors and Its Pathogenecity)
19 pages, 540 KiB  
Review
Candida albicans Antifungal Resistance and Tolerance in Bloodstream Infections: The Triad Yeast-Host-Antifungal
by Sofia Costa-de-Oliveira and Acácio G. Rodrigues
Microorganisms 2020, 8(2), 154; https://doi.org/10.3390/microorganisms8020154 - 22 Jan 2020
Cited by 99 | Viewed by 9869
Abstract
Candida albicans represents the most frequent isolated yeast from bloodstream infections. Despite the remarkable progress in diagnostic and therapeutic approaches, these infections continue to be a critical challenge in intensive care units worldwide. The economic cost of bloodstream fungal infections and its associated [...] Read more.
Candida albicans represents the most frequent isolated yeast from bloodstream infections. Despite the remarkable progress in diagnostic and therapeutic approaches, these infections continue to be a critical challenge in intensive care units worldwide. The economic cost of bloodstream fungal infections and its associated mortality, especially in debilitated patients, remains unacceptably high. Candida albicans is a highly adaptable microorganism, being able to develop resistance following prolonged exposure to antifungals. Formation of biofilms, which diminish the accessibility of the antifungal, selection of spontaneous mutations that increase expression or decreased susceptibility of the target, altered chromosome abnormalities, overexpression of multidrug efflux pumps and the ability to escape host immune defenses are some of the factors that can contribute to antifungal tolerance and resistance. The knowledge of the antifungal resistance mechanisms can allow the design of alternative therapeutically options in order to modulate or revert the resistance. We have focused this review on the main factors that are involved in antifungal resistance and tolerance in patients with C. albicans bloodstream infections. Full article
(This article belongs to the Special Issue Candida albicans Virulence Factors and Its Pathogenecity)
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14 pages, 1216 KiB  
Review
Recurrent Vulvovaginal Candidiasis: An Immunological Perspective
by Diletta Rosati, Mariolina Bruno, Martin Jaeger, Jaap ten Oever and Mihai G. Netea
Microorganisms 2020, 8(2), 144; https://doi.org/10.3390/microorganisms8020144 - 21 Jan 2020
Cited by 86 | Viewed by 11189
Abstract
Vulvovaginal candidiasis (VVC) is a widespread vaginal infection primarily caused by Candida albicans. VVC affects up to 75% of women of childbearing age once in their life, and up to 9% of women in different populations experience more than three episodes per [...] Read more.
Vulvovaginal candidiasis (VVC) is a widespread vaginal infection primarily caused by Candida albicans. VVC affects up to 75% of women of childbearing age once in their life, and up to 9% of women in different populations experience more than three episodes per year, which is defined as recurrent vulvovaginal candidiasis (RVVC). RVVC results in diminished quality of life as well as increased associated healthcare costs. For a long time, VVC has been considered the outcome of inadequate host defenses against Candida colonization, as in the case of primary immunodeficiencies associated with persistent fungal infections and insufficient clearance. Intensive research in recent decades has led to a new hypothesis that points toward a local mucosal overreaction of the immune system rather than a defective host response to Candida colonization. This review provides an overview of the current understanding of the host immune response in VVC pathogenesis and suggests that a tightly regulated fungus–host–microbiota interplay might exert a protective role against recurrent Candida infections. Full article
(This article belongs to the Special Issue Candida albicans Virulence Factors and Its Pathogenecity)
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