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FEMS Microbiology Reviews Mar 2012The incidence of infections caused by Candida species (candidosis) has increased considerably over the past three decades, mainly due to the rise of the AIDS epidemic,... (Review)
Review
The incidence of infections caused by Candida species (candidosis) has increased considerably over the past three decades, mainly due to the rise of the AIDS epidemic, an increasingly aged population, higher numbers of immunocompromised patients and the more widespread use of indwelling medical devices. Candida albicans is the main cause of candidosis; however, non-C. albicans Candida (NCAC) species such as Candida glabrata, Candida tropicalis and Candida parapsilosis are now frequently identified as human pathogens. The apparent increased emergence of these species as human pathogens can be attributed to improved identification methods and also associated with the degree of diseases of the patients, the interventions that they were subjected and the drugs used. Candida pathogenicity is facilitated by a number of virulence factors, most importantly adherence to host surfaces including medical devices, biofilm formation and secretion of hydrolytic enzymes (e.g. proteases, phospholipases and haemolysins). Furthermore, despite extensive research to identify pathogenic factors in fungi, particularly in C. albicans, relatively little is known about NCAC species. This review provides information on the current state of knowledge on the biology, identification, epidemiology, pathogenicity and antifungal resistance of C. glabrata, C. parapsilosis and C. tropicalis.
Topics: Animals; Antifungal Agents; Candida; Candida glabrata; Candida tropicalis; Candidiasis; Drug Resistance, Fungal; Humans
PubMed: 21569057
DOI: 10.1111/j.1574-6976.2011.00278.x -
Clinical Microbiology and Infection :... Jul 2019Recently there has been an increase in Candida infections worldwide. A handful of species in the genus Candida are opportunistic pathogens and have been known to cause... (Review)
Review
BACKGROUND
Recently there has been an increase in Candida infections worldwide. A handful of species in the genus Candida are opportunistic pathogens and have been known to cause infections in immunocompromised or otherwise impaired hosts. These infections can be superficial, affecting the skin or mucous membrane, or invasive, which can be life-threatening. Azoles and echinocandins are antifungal drugs used globally to treat Candida infections. However, resistance to these antifungal drugs has increased in many of the Candida species, and the effects this has in the clinical setting can be seen.
OBJECTIVES
Here, we discuss the mechanisms that Candida albicans, Candida dubliniensis, Candida glabrata, Candida parapsilosis, Candida tropicalis and Candida auris are implementing to increase resistance to azoles and echinocandins, and how they are affecting clinical, or hospital, settings worldwide.
SOURCES
Different studies and papers describing the mechanisms of antifungal drugs and Candida species evolution to becoming resistant to these drugs were looked at for this review.
CONTENT
We discuss the mechanisms that azoles and echinocandins use against Candida species to treat infections, as well as the evolution of these fungi to become resistant to these drugs, and the effect this has in the clinical settings around the globe.
IMPLICATIONS
Increased resistance to azoles and echinocandins by Candida species is an increasingly serious problem in clinical settings worldwide. Understanding the mechanisms used against antifungal drugs is imperative for patient treatment.
Topics: Antifungal Agents; Azoles; Candida; Candida albicans; Candida glabrata; Drug Resistance, Multiple, Fungal; Echinocandins; Humans; Microbial Sensitivity Tests
PubMed: 30965100
DOI: 10.1016/j.cmi.2019.03.028 -
Virulence Nov 2017
Topics: Candida; Candida glabrata; Candidiasis; Humans; Lectins, C-Type
PubMed: 28727942
DOI: 10.1080/21505594.2017.1358350 -
FEMS Yeast Research Jan 2022Invasive candidiasis, the most frequent healthcare-associated invasive fungal infection, is commonly caused by Candida albicans. However, in recent years other... (Review)
Review
Invasive candidiasis, the most frequent healthcare-associated invasive fungal infection, is commonly caused by Candida albicans. However, in recent years other antifungal-resistant Candida species-namely Candida glabrata and Candidaauris-have emerged as a serious matter of concern. Much of our understanding of the mechanisms regulating antifungal resistance and tolerance relies on studies utilizing C. albicans, C. glabrataand the model yeast Saccharomyces cerevisiae. 'Omics studies have been used to describe alterations in metabolic, genomic and transcriptomic expression profiles upon antifungal treatment of fungal cells. The physiological changes identified by these approaches could significantly affect fungal fitness in the host and survival during antifungal challenge, as well as provide further understanding of clinical resistance. Thus, this review aims to comparatively address 'omics data for C. albicans, C. glabrata andS. cerevisiae published from 2000 to 2021 to identify what these technologies can tell us regarding cellular responses to antifungal therapy. We will also highlight possible effects on pathogen survival and identify future avenues for antifungal research.
Topics: Antifungal Agents; Candida albicans; Candida glabrata; Candidiasis; Drug Resistance, Fungal; Humans; Microbial Sensitivity Tests
PubMed: 34958354
DOI: 10.1093/femsyr/foab070 -
FEMS Yeast Research Sep 2015In recent years, there has been a noticeable rise in fungal infections related to non-albicans Candida species, including Candida glabrata which has both intrinsic... (Review)
Review
In recent years, there has been a noticeable rise in fungal infections related to non-albicans Candida species, including Candida glabrata which has both intrinsic resistance to and commonly acquired resistance to azole antifungals. Phylogenetically, C. glabrata is more closely related to the mostly non-pathogenic model organism Saccharomyces cerevisiae than to other Candida species. Despite C. glabrata's designation as a pathogen by Wickham in 1957, relatively little is known about its mechanism of virulence. Over the past few years, technology to analyse the molecular basis of infection has developed rapidly, and here we briefly review the major advances in tools and technologies available to explore and investigate the virulence of C. glabrata that have occurred over the past decade.
Topics: Animals; Candida glabrata; Candidiasis; Disease Models, Animal; Genetics, Microbial; Humans; Molecular Biology; Virulence; Virulence Factors
PubMed: 26205243
DOI: 10.1093/femsyr/fov066 -
MSphere Aug 2022The human fungal pathogen Candida glabrata is phylogenetically closely related to Saccharomyces cerevisiae, a model eukaryotic organism. Unlike S. cerevisiae, which has...
The human fungal pathogen Candida glabrata is phylogenetically closely related to Saccharomyces cerevisiae, a model eukaryotic organism. Unlike S. cerevisiae, which has both haploid and diploid forms and a complete sexual cycle, C. glabrata has long been considered a haploid and asexual species. In this study, we analyzed the ploidy states of 500 clinical isolates of C. glabrata from four Chinese hospitals and found that approximately 4% of the isolates were in or able to spontaneously switch to an aneuploid (genomic DNA, 1N-2N), diploid (2N), or hyperdiploid (>2N) form under or conditions. Stable diploid cells were identified in 3% of the isolates (15/500). Of particular interest, one clinical strain existed only in the diploid form. Multilocus sequence typing (MLST) assays revealed two major genetic clusters (A and B) of C. glabrata isolates. Most of the isolates (70%) from China belonged to the A cluster, whereas most of the isolates from other countries (such as Iran, Japan, United States, and European countries) belonged to the B cluster. Further investigation indicated that C. glabrata cells of different ploidy forms differed in a number of respects, including morphologies, antifungal susceptibility, virulence, and global gene expression profiles. Additionally, C. glabrata could undergo spontaneous switching between the diploid and haploid forms under both and conditions. Given the absence of an apparent sexual phase, one would expect that the ploidy shifts could function as an alternative strategy that promotes genetic diversity and benefits the ability of the fungus to rapidly adapt to the changing environment. The human fungal pathogen Candida glabrata has long been thought to be a haploid organism. Here, we report the population structure and ploidy states of 500 clinical isolates of C. glabrata from China. To our surprise, we found that the ploidy of a subset of clinical isolates varied dramatically. Some isolates were in or able to switch to an aneuploid, diploid, or hyperdiploid form. C. glabrata cells with different ploidy differed in a number of biological respects, including morphology, antifungal susceptibility, virulence, and global gene expression profile. Given the absence of an apparent sexual phase in this fungus, we propose that ploidy switching could be a strategy for rapid adaptation to environmental changes and could function as an alternative to sexual reproduction.
Topics: Aneuploidy; Antifungal Agents; Candida glabrata; Diploidy; Haploidy; Humans; Multilocus Sequence Typing; Saccharomyces cerevisiae
PubMed: 35727043
DOI: 10.1128/msphere.00260-22 -
Cold Spring Harbor Perspectives in... Sep 2014Candida species are the most common causes of fungal infection. Approximately 90% of infections are caused by five species: Candida albicans, Candida glabrata, Candida... (Review)
Review
Candida species are the most common causes of fungal infection. Approximately 90% of infections are caused by five species: Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, and Candida krusei. Three (C. albicans, C. tropicalis, and C. parapsilosis) belong to the CTG clade, in which the CTG codon is translated as serine and not leucine. C. albicans remains the most commonly isolated but is decreasing relative to the other species. The increasing incidence of C. glabrata is related to its reduced susceptibility to azole drugs. Genome analysis suggests that virulence in the CTG clade is associated with expansion of gene families, particularly of cell wall genes. Similar independent processes took place in the C. glabrata species group. Gene loss and expansion in an ancestor of C. glabrata may have resulted in preadaptations that enabled pathogenicity.
Topics: Candida glabrata; Candidiasis; Global Health; Humans; Prevalence; Virulence
PubMed: 25183855
DOI: 10.1101/cshperspect.a019778 -
Infection and Immunity Feb 2021The mechanisms by which resists host defense peptides and caspofungin are incompletely understood. To identify transcriptional regulators that enable to withstand... (Comparative Study)
Comparative Study
The mechanisms by which resists host defense peptides and caspofungin are incompletely understood. To identify transcriptional regulators that enable to withstand these classes of stressors, a library of 215 transcriptional regulatory deletion mutants was screened for susceptibility to both protamine and caspofungin. We identified eight mutants that had increased susceptibility to both host defense peptides and caspofungin. Of these mutants, six were deleted for genes that were predicted to specify proteins involved in histone modification. These genes were , , , , , and Deletion of , , and also increased susceptibility to mammalian host defense peptides. The Δ and Δ mutants had increased susceptibility to other stressors, such as HO and SDS. In the model of disseminated infection, the Δ and Δ mutants had attenuated virulence, whereas in neutropenic mice, the virulence of the Δ and Δ mutants was decreased. Thus, histone modification plays a central role in enabling to survive host defense peptides and caspofungin, and Ada2 and Rpd3 are essential for the maximal virulence of this organism during disseminated infection.
Topics: Candida glabrata; Fungal Proteins; Gene Deletion; Genetic Variation; Host-Pathogen Interactions; Humans; Mutation; Transcription Factors; Virulence
PubMed: 33318139
DOI: 10.1128/IAI.00146-20 -
FEMS Yeast Research Jun 2014The yeast pathogen Candida glabrata is the second most frequent cause of Candida infections. However, from the phylogenetic point of view, C. glabrata is much closer to... (Review)
Review
The yeast pathogen Candida glabrata is the second most frequent cause of Candida infections. However, from the phylogenetic point of view, C. glabrata is much closer to Saccharomyces cerevisiae than to Candida albicans. Apparently, this yeast has relatively recently changed its life style and become a successful opportunistic pathogen. Recently, several C. glabrata sister species, among them clinical and environmental isolates, have had their genomes characterized. Also, hundreds of C. glabrata clinical isolates have been characterized for their genomes. These isolates display enormous genomic plasticity. The number and size of chromosomes vary drastically, as well as intra- and interchromosomal segmental duplications occur frequently. The observed genome alterations could affect phenotypic properties and thus help to adapt to the highly variable and harsh habitats this yeast finds in different human patients and their tissues. Further genome sequencing of pathogenic isolates will provide a valuable tool to understand the mechanisms behind genome dynamics and help to elucidate the genes contributing to the virulence potential.
Topics: Adaptation, Biological; Candida glabrata; Gene Order; Gene Rearrangement; Genome, Fungal; Genomic Structural Variation
PubMed: 24528571
DOI: 10.1111/1567-1364.12145 -
Cellular Microbiology May 2013Candida albicans and C. glabrata are the two most common pathogenic yeasts of humans, yet they are phylogenetically, genetically and phenotypically very different. In... (Review)
Review
Candida albicans and C. glabrata are the two most common pathogenic yeasts of humans, yet they are phylogenetically, genetically and phenotypically very different. In this review, we compare and contrast the strategies of C. albicans and C. glabrata to attach to and invade into the host, obtain nutrients and evade the host immune response. Although their strategies share some basic concepts, they differ greatly in their outcome. While C. albicans follows an aggressive strategy to subvert the host response and to obtain nutrients for its survival, C. glabrata seems to have evolved a strategy which is based on stealth, evasion and persistence, without causing severe damage in murine models. However, both fungi are successful as commensals and as pathogens of humans. Understanding these strategies will help in finding novel ways to fight Candida, and fungal infections in general.
Topics: Candida albicans; Candida glabrata; Candidiasis; Cell Adhesion; Host-Pathogen Interactions; Humans; Phylogeny
PubMed: 23253282
DOI: 10.1111/cmi.12091