Candida Auris
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''Candida auris'' is a
species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate s ...
of
fungus A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from t ...
that grows as
yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constit ...
. It is one of the few species of the genus '' Candida'' which cause
candidiasis Candidiasis is a fungal infection due to any type of '' Candida'' (a type of yeast). When it affects the mouth, in some countries it is commonly called thrush. Signs and symptoms include white patches on the tongue or other areas of the mouth ...
in humans. Often, candidiasis is acquired in hospitals by patients with weakened immune systems. ''C.auris'' can cause invasive candidiasis ( fungemia) in which the
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
stream, the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
, and internal
organs In biology, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to act together in a f ...
are infected. It has attracted widespread attention because of its
multiple drug resistance Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to at least one antimicrobial drug in three or more antimicrobial categories. Antimicrobial categories are c ...
. Treatment is also complicated because it is easily misidentified as other ''Candida'' species. ''Candida auris'' was first described in 2009 after it was isolated from the ear canal of a 70-year-old Japanese woman at the Tokyo Metropolitan Geriatric Hospital in Japan. In 2011, South Korea saw its first cases of disease-causing ''C.auris''. Reportedly, this spread across Asia and Europe, and first appeared in the U.S. in 2013. DNA analysis of four distinct but drug-resistant strains of ''Candida auris'' indicate an evolutionary divergence taking place at least 4,000 years ago, with a common leap among the four varieties into drug-resistance possibly linked to widespread azole-type antifungal use in agriculture. However, explanations for its emergence remain speculative.


Identification and morphology

First identified in 2009, ''Candida auris'' is a
species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate s ...
of ascomycetous fungus of the genus '' Candida'' that grows as a
yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constit ...
. Its name comes from the Latin word for ear, ''auris''. It forms smooth, shiny, whitish-gray, viscous colonies on growth media. Microscopically cells are ellipsoid in shape.


Clinical significance

''Candida auris'' has attracted increased clinical attention because of its
multiple drug resistance Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to at least one antimicrobial drug in three or more antimicrobial categories. Antimicrobial categories are c ...
. In vitro, more than 90% of ''C.auris'' isolates are resistant to
fluconazole Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor. It is also used to pr ...
and a range of 3–73% of ''C.auris'' isolates are resistant to
voriconazole Voriconazole, sold under the brand name Vfend among others, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, candidiasis, coccidioidomycosis, histoplasmosis, penicilliosis, and infections by ...
, while other triazoles (
posaconazole Posaconazole, sold under the brand name Noxafil among others, is a triazole antifungal medication. It was approved for medical use in the United States in September 2006, and is available as a generic medication. Medical uses Posaconazole is u ...
,
itraconazole Itraconazole, sometimes abbreviated ITZ, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, blastomycosis, coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis. It may be given by mo ...
, and
isavuconazole Isavuconazonium sulfate, sold under the brand name Cresemba, is a systemic antifungal medication of the triazole class which is used to treat invasive aspergillosis and mucormycosis. The most common side effects include abnormal liver tests, ...
) display better activity. Of isolates, 13% to 35% were reported resistant to amphotericin B; however, most isolates are susceptible to echinocandins. Treatment is complicated because ''C.auris'' is easily misidentified as various other ''Candida'' species. A brief outline of its clinical relevance , understandable by general audiences, was published by the
Center for Infectious Disease Research and Policy The Center for Infectious Disease Research and Policy (CIDRAP) is a center within the University of Minnesota that focuses on addressing public health preparedness and emerging infectious disease response. It was founded in 2001 by Dr. Michael Os ...
at the University of Minnesota. According to the
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
(CDC), 30–60% of people with ''C.auris'' bloodstream infections (BSI) have died. However, many of these people had other serious illnesses and conditions (comorbidities) that also increased their risk of death.


Vaccine development

There is currently no vaccine for ''Candida auris,'' however, attempts have been made, with experiments involving the NDV-3A vaccine that successfully immunized mice against the fungus. The vaccine also improved the protective efficacy of the antifungal drug micafungin against ''C. auris'' infection in the bloodstream.


Genome

Several draft
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding g ...
s from
whole genome sequencing Whole genome sequencing (WGS), also known as full genome sequencing, complete genome sequencing, or entire genome sequencing, is the process of determining the entirety, or nearly the entirety, of the DNA sequence of an organism's genome at a ...
have been published. ''C.auris'' has a genome size of 12.3–12.5 with a GC-content of 44.5–44.8%. The ''C.auris'' genome was found to encode several genes for the ABC transporter family, a
major facilitator superfamily The major facilitator superfamily (MFS) is a superfamily of membrane transport proteins that facilitate movement of small solutes across cell membranes in response to chemiosmotic gradients. Function The major facilitator superfamily (MFS) are ...
, which helps to explain its
multiple drug resistance Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to at least one antimicrobial drug in three or more antimicrobial categories. Antimicrobial categories are c ...
. Its genome also encodes virulence-related gene families such as lipases, oligopeptide transporters, mannosyl transferases and
transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...
s which facilitate colonization, invasion, and iron acquisition. Another factor contributing to antifungal resistance is the presence of a set of genes known to be involved in
biofilm A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular ...
formation. More studies are needed to determine whether the phylogenetic divergence of ''C.auris'' clones exhibits region-specific patterns of invasiveness, virulence, and/or drug resistance.


Epidemiology


Geographical differentiation

The
phylogenetics In biology, phylogenetics (; from Greek φυλή/ φῦλον [] "tribe, clan, race", and wikt:γενετικός, γενετικός [] "origin, source, birth") is the study of the evolutionary history and relationships among or within groups ...
of ''C.auris'' suggest distinct genotypes exist in different geographical regions with substantial genomic diversity. A variety of sequence-based analytical methods have been used to support this finding.
Whole genome sequencing Whole genome sequencing (WGS), also known as full genome sequencing, complete genome sequencing, or entire genome sequencing, is the process of determining the entirety, or nearly the entirety, of the DNA sequence of an organism's genome at a ...
and analyses of isolates from Pakistan, India, South Africa, Venezuela, Japan, and previously sequenced ''C.auris'' genomes deposited in the
National Center for Biotechnology Information The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health (NIH). It is approved and funded by the government of the United States. The ...
's Sequence Read Archive identified a distinct geographic distribution of genotypes. Four distinct clades separated by tens of thousands of
single-nucleotide polymorphism In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently lar ...
s were identified. The distribution of these clades segregated geographically to South Asia (India and Pakistan), South Africa, Venezuela, and Japan with minimal observed intraregion genetic diversity.
Amplified fragment length polymorphism AFLP-PCR or just AFLP is a PCR-based tool used in genetics research, DNA fingerprinting, and in the practice of genetic engineering. Developed in the early 1990s by KeyGene, AFLP uses restriction enzymes to digest genomic DNA, followed by liga ...
analysis of ''C.auris'' isolates from the United Kingdom, India, Japan, South Africa, South Korea, and Venezuela suggested that the London isolates formed a distinct cluster compared to the others. Comparison of
ribosomal DNA Ribosomal DNA (rDNA) is a DNA sequence that codes for ribosomal RNA. These sequences regulate transcription initiation and amplification, and contain both transcribed and non-transcribed spacer segments. In the human genome there are 5 chromo ...
sequences of ''C.auris'' isolates from Israel, Asia, South Africa, and Kuwait found that the strains from Israel were phylogenetically distinct from those from the other regions. Chatterjee et al. wrote in 2015, "Its actual global distribution remains obscure as the current commercial methods of clinical diagnosis misidentify it as ''C.haemulonii''."


History

''Candida auris'' was first described in 2009 after it was isolated from the ear canal of a 70-year-old Japanese woman at the Tokyo Metropolitan Geriatric Hospital in Japan. It was isolated based on its ability to grow in the presence of the fungicide
micafungin Micafungin, sold under the brand name Mycamine, is an echinochandin antifungal medication used to treat and prevent invasive fungal infections including candidemia, abscesses, and esophageal candidiasis. It inhibits the production of beta-1,3- ...
, an echinocandin class fungicide. Phenotypic, chemotaxonomic and phylogenetic analyses established ''C.auris'' as a new strain of the genus ''Candida''. The first three cases of disease-causing ''C.auris'' were reported from South Korea in 2011. Two isolates had been obtained during a 2009 study and a third was discovered in a stored sample from 1996. All three cases had persistent fungemia, i.e. bloodstream infection, and two of the patients subsequently died due to complications. Notably, the isolates initially were misidentified as ''Candida haemulonii'' and '' Rhodotorula glutinis'' using standard methods, until sequence analysis correctly identified them as ''C.auris''. These first cases emphasize the importance of accurate species identification and timely application of the correct antifungal for the effective treatment of candidiasis with ''C.auris''. During 2009–2011, 12 ''C.auris'' isolates were obtained from patients at two hospitals in Delhi, India. The same genotype was found in distinct settings: intensive care, surgical, medical, oncologic, neonatal, and pediatric wards, which were mutually exclusive with respect to health care personnel. Most had persistent candidemia and a high mortality rate was observed. All isolates were of the same clonal strain, however, and were only identified positively by DNA sequence analysis. As previously, the strain was misidentified with established diagnostic laboratory tests. The Indian researchers wrote in 2013 that ''C.auris'' was much more prevalent than published reports indicate since most diagnostic laboratories do not use sequence-based methods for strain identification. The fungus spread to other continents and eventually, a multi-drug-resistant strain was discovered in Southeast Asian countries in early 2016. The first report of a ''C.auris'' outbreak in
Europe Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a subcontinent of Eurasia and it is located entirel ...
was an October 2016 in
Royal Brompton Hospital Royal Brompton Hospital is the largest specialist heart and lung medical centre in the United Kingdom. It is managed by Guy's and St Thomas' NHS Foundation Trust. History Consumption in the 19th Century In the 19th century, consumption was a c ...
, a London cardio-thoracic hospital. In April 2017,
CDC The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
director
Anne Schuchat Anne Schuchat (born 1960) is an American medical doctor. She is a former rear admiral and assistant surgeon general in the United States Public Health Service Commissioned Corps. She also served as the principal deputy director of the Centers f ...
named it a "catastrophic threat". the CDC had reported 77 cases in the United States. Of these, 69 were from samples collected in New York and New Jersey. the number of cases of people having contracted ''C.auris'' in the United States had risen to 806, with 388 reported in New York, 137 in New Jersey and 227 in Illinois, according to the CDC. Since it was first observed in the United Kingdom, it has spread to more than 20
NHS Trust An NHS trust is an organisational unit within the National Health Services of England and Wales, generally serving either a geographical area or a specialised function (such as an ambulance service). In any particular location there may be several ...
hospitals and infected 200 people. , the CDC has documented cases of ''C.auris'' from the following countries: Australia, Austria, Belgium, Canada, China, Colombia, France, Germany, India, Iran, Israel, Japan, Kenya, Kuwait, Malaysia, Mexico, the Netherlands, Norway, Oman, Pakistan, Panama, Russia, Saudi Arabia, Singapore, South Africa, South Korea, Spain, Switzerland, Taiwan, Thailand, the United Arab Emirates, the United Kingdom, the United States, and Venezuela.
''Candida auris'' fungus (''C. auris'') is a multi-drug–resistant fungal infection that spreads in hospitals and is extremely deadly—killing as many as one in three who get it. :—Abby Haglage of Yahoo! Lifestyle, citing the
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
Arturo Casadevall, MD, PhD, and Molecular Microbiology and Immunology chair at Johns Hopkins Bloomberg School of Public Health stated:
What this study suggests is this is the beginning of fungi adapting to higher temperatures, and we are going to have more and more problems as the century goes on. Global warming will lead to selection of fungal lineages that are more thermally tolerant.
The
COVID-19 pandemic The COVID-19 pandemic, also known as the coronavirus pandemic, is an ongoing global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel virus was first identi ...
has taken resources away from combating and tracking the fungus, which has led to outbreaks. Shortages of
personal protective equipment Personal protective equipment (PPE) is protective clothing, helmets, goggles, or other garments or equipment designed to protect the wearer's body from injury or infection. The hazards addressed by protective equipment include physical, e ...
forced medical personnel to reuse of gowns and masks during the pandemic, which has contributed to the fungi's spread. In 2021, the CDC identified strains of ''Candida auris'' that were immune to all existing medications used to treat fungal infections.


Context

Antimicrobial resistance Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. P ...
in general is an increasingly common phenomenon. In 2010, two million people were reported to have contracted resistant infections in the United States 23,000 fatally. " re recent estimates from researchers at
Washington University School of Medicine Washington University School of Medicine (WUSM) is the medical school of Washington University in St. Louis in St. Louis, Missouri. Founded in 1891, the School of Medicine has 1,260 students, 604 of which are pursuing a medical degree with ...
put the death toll at 162,000. Worldwide fatalities from resistant infections are estimated at 700,000 per year. ''C. auris'' is one of the many microbial contributors to this global AMR estimation.


See also

* '' Candida blankii''


References


Notes


Citations


External links


''Candida'' Genome Database
{{Taxonbar, from=Q26816853 21st-century epidemics Antimicrobial resistance auris Pathogenic microbes Yeasts