Open Forum Infectious Diseases
`R E V I E W A R T I C L E I N V I T E D
`
`Downloaded from https://academic.oup.com/ofid/article/10/1/ofac559/6974385 by The University of Texas at Austin user on 03 July 2024
`
`Fungal Nomenclature: Managing Change is the Name
`of the Game
`
`Sarah E. Kidd,1,2, Alireza Abdolrasouli,3,4, and Ferry Hagen5,6,7,
`1National Mycology Reference Centre, SA Pathology, Adelaide, South Australia, Australia, 2School of Biological Sciences, Faculty of Sciences, University of Adelaide, Adelaide, South Australia,
`Australia, 3Department of Medical Microbiology, King’s College Hospital, London, United Kingdom, 4Department of Infectious Diseases, Imperial College London, London, United Kingdom,
`5Westerdijk Fungal Biodiversity Institute, Utrecht, The Netherlands, 6Institute of Biodiversity and Ecosystem Dynamics, University of Amsterdam, Amsterdam, The Netherlands, and 7Department of
`Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands
`
`Fungal species have undergone and continue to undergo significant nomenclatural change, primarily due to the abandonment of
`dual species nomenclature in 2013 and the widespread application of molecular technologies in taxonomy allowing correction of
`past classification errors. These have effected numerous name changes concerning medically important species, but by far the group
`causing most concern are the Candida yeasts. Among common species, Candida krusei, Candida glabrata, Candida guilliermondii,
`Candida lusitaniae, and Candida rugosa have been changed to Pichia kudriavzevii, Nakaseomyces glabrata, Meyerozyma
`guilliermondii, Clavispora lusitaniae, and Diutina rugosa, respectively. There are currently no guidelines for microbiology
`laboratories on implementing changes, and there is ongoing concern that clinicians will dismiss or misinterpret laboratory
`reports using unfamiliar species names. Here, we have outlined the rationale for name changes across the major groups of
`clinically important fungi and have provided practical recommendations for managing change.
`Keywords. Candida; clinical fungi; nomenclature; taxonomy.
`
`If we accept that the only constant in life is change, we can be-
`gin to understand that fungal name changes always have and
`always will occur. Fungal nomenclature has been undergoing
`extensive change for more than a decade. This can largely be at-
`tributed to the now commonplace role of molecular-based
`technologies in taxonomy, diagnostics, and epidemiology.
`Molecular studies have improved the way in which fungal spe-
`cies are defined and identified, permitting refinement of inter-
`and intraspecies phylogenetic relationships and correction of
`taxonomical errors arising from the phenotypic classification
`and identification methods used in the past. For this reason,
`the long-held convention of fungal species having 2 or more
`valid names for their teleomorph (sexual) and anamorph (asex-
`ual) states was abandoned in 2013 [1]. The subsequent need to
`rationalize existing names meant that some names in common
`use have been retained, whereas in other cases they have been
`replaced by the less commonly used name. Additional impacts
`of molecular studies include revealing extensive genetic
`
`Received 31 August 2022; editorial decision 14 October 2022; accepted 18 October 2022
`Correspondence: Sarah E. Kidd, BMedSc(Hons), PhD , National Mycology Reference Centre,
`SA Pathology, Frome Road, Adelaide, South Australia 5000, Australia (sarah.kidd@sa.gov.au).
`Open Forum Infectious Diseases®
`© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases
`Society of America. This is an Open Access article distributed under the terms of the
`Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.
`org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of
`the work, in any medium, provided the original work is not altered or transformed in any
`way, and that the work is properly cited. For commercial re-use, please contact journals.permis-
`sions@oup.com
`https://doi.org/10.1093/ofid/ofac559
`
`variation within species that were originally ascribed by their
`morphology, leading to the description of additional species
`within them. Molecular analyses have shone a light on whether
`taxonomic groups that have been classified and named on the
`basis of shared morphological or phenotypic features actually
`share a single common ancestor (monophyletic) or whether
`the species have mixed ancestry such that not all species within
`the group are related (polyphyletic). In the case of polyphyletic
`genera, transfer of those species that do not share common an-
`cestry into a more appropriate genus is warranted.
`These changes form a critical part of an ongoing process of
`refinement in the way that we understand organisms to have
`evolved, to interact, and to behave. Changes in fungal species
`names have been occurring at a rapid pace over the past decade
`[2–4], and this has led to some heated debate in the arena of so-
`cial media [5, 6] on the benefits and difficulties caused by such
`changes in clinical practice. Commonly the name change af-
`fects the genus, but the species epithet remains recognizable
`(eg, Scedosporium prolificans became Lomentospora prolifi-
`cans), but this is not always the case (eg, Candida krusei became
`Pichia kudriavzevii); anecdotally, it seems to be the latter situa-
`tion causing most concern. It is important to note that fungal
`nomenclature changes must strictly follow the International
`Code of Nomenclature for algae, fungi, and plants [7], and
`any wish to preserve certain names or parts thereof, is overrid-
`den by the nomenclatural priority of previous legitimate names
`for the species. However, nomenclatural changes are not new
`or unique to fungi, and numerous species name changes in
`the past have been accepted and embedded into clinical
`
`Fungal Nomenclature • OFID • 1
`
`LCY Biotechnology Holding, Inc.
`Ex. 1039
`Page 1 of 15
`
`

`

`Downloaded from https://academic.oup.com/ofid/article/10/1/ofac559/6974385 by The University of Texas at Austin user on 03 July 2024
`
`Candida pararugosa, Candida neorugosa, and Candida pseu-
`dorugosa [14, 15]; these species, along with Candida catenulata
`and Candida scorzettiae, form a well-separated clade and were
`transferred to a new genus as Diutina [14]. Other new genera
`containing former Candida species include Debaryomyces,
`Clavispora, Kluyveromyces, Meyerozyma, Wickerhamomyces,
`and Yarrowia. Table 1 summarizes nomenclature changes to
`date in clinically important yeasts.
`Several pathogenic Candida species have been described in
`recent years. Without a doubt, Candida auris, described in
`2009 as part of the Candida haemulonii complex, has become
`the most notorious of these [22]. Candida auris has been asso-
`ciated with large healthcare-related outbreaks globally, and
`comprises 4 major lineages, each having their own antifungal
`susceptibility characteristics [23, 24]. Other members of this
`species complex are Candida duobushaemulonii and Candida
`vulturna [25, 26]. The latter was indicated as C vulturna pro
`tempore, indicating that “Candida” is a temporary solution.
`In fact, these species all cluster within the Clavispora clade [8],
`suggesting that a name change may be warranted. Candida
`blankii was described in 1968 but has only recently been recog-
`nized as a multidrug-resistant human pathogen [27–31]. It does
`not group in any of the Candida clades and may, therefore, be
`the sole representative of an as yet undescribed genus [9].
`
`Cryptococcus
`The basidiomycetous yeasts have also undergone substantial
`taxonomic change based on large-scale phylogenetic evidence
`[18, 32]. The revision of the genus Cryptococcus coincided
`with the proposal to elevate the 7 lineages within the
`Cryptococcus neoformans and Cryptococcus gattii complexes
`to species [33], which, while now largely accepted, has not
`been without robust debate [34, 35]. Besides 3 nonpathogenic
`Cryptococcus species, the genus now contains the major cause
`of cryptococcosis: C neoformans sensu stricto (previously
`C neoformans var grubii) and Cryptococcus deneoformans
`(previously C neoformans var neoformans). Two of 5 pathogen-
`ic species within the C gattii complex were renamed to a
`previously published synonym: C gattii sensu stricto (genotype
`AFLP4/VGI) and Cryptococcus bacillisporus (AFLP5/VGIII),
`and Cryptococcus deuterogattii (AFLP6/VGII), Cryptococcus
`tetragattii
`(AFLP7/VGIV), and Cryptococcus decagattii
`(AFLP10/VGVI) were named for their molecular type [33].
`Epidemiological studies indicate that various Cryptococcus spe-
`cies have a predilection for certain hosts and exhibit differences
`in antifungal susceptibility [33]. While identification platforms
`such as matrix-assisted laser desorption/ionization–time of
`flight mass spectrometry (MALDI-TOF MS) have the capabil-
`ity to differentiate and identify these species using in-house da-
`tabases, this may not be accessible to many laboratories on a
`routine basis; in such cases the organism could be reported as
`C gattii complex or C neoformans complex as appropriate.
`
`practice. Here we review nomenclature changes in clinically
`important fungi over the past 20 years and make recommenda-
`tions on incorporating nomenclature change into laboratory
`reporting and clinical practice.
`
`YEASTS AND YEAST-LIKE FUNGI
`
`Candida
`Arguably the group of fungi undergoing the most reclassification
`in recent times and causing most concern among clinicians and
`medical laboratorians is the ascomycetous yeasts, and particularly
`Candida, likely because these are a common cause of invasive and
`superficial infections encountered in both specialized and nonspe-
`cialized microbiology laboratories worldwide. The problem with
`Candida is that it represents a large, highly polyphyletic group
`of budding, white colony-forming yeasts in the subphylum
`Saccharomycotina, originally grouped together because of their
`similar morphology and lack of a defined teleomorph [8–10]. It
`does not meet the 3 generally accepted criteria of a genus: (1)
`monophyly, that is, all species within it evolving from a common
`ancestor; (2) reasonable compactness in terms of the number of
`species it encompasses; and (3) members of the genus share evo-
`lutionarily derived characteristics [11]. Extensive phylogenetic
`study of species within the Candida group has revealed a number
`of well-supported clades that better fit the definition of a genus [8–
`10]. Figure 1 provides an overview of the relationship between
`clades within the Candida group. Three of the most common
`Candida pathogens are Candida albicans, Candida parapsilosis,
`and Candida tropicalis, which fall into the Lodderomyces clade;
`this clade contains generally antifungal-susceptible Candida spe-
`cies [10]. Being among the largest clades with demonstrated
`monophyly, this clade has retained the name Candida.
`However, Candida glabrata, along with the closely related species
`Candida bracarensis and Candida nivariensis, form part of the
`Nakaseomyces clade, and hence have been transferred to a new ge-
`nus, Nakaseomyces, as Nakaseomyces glabrata, Nakaseomyces bra-
`carensis, and Nakaseomyces nivariensis, respectively, although
`formal description is still pending [4]. Candida krusei, at one point
`also being known concurrently by Issatchenckia orientalis,
`Candida glycerinogenes, and Pichia kudriavzevii [12], belongs to
`the Pichia clade and was formally described as P kudriavzevii
`due to the nomenclatural priority of this name over others.
`Candida norvegensis also forms part of the Pichia clade, and has
`to Pichia norvegensis
`the
`[13]. Both
`been
`transferred
`Nakaseomyces and Pichia clades include species characterized
`by decreased susceptibility or intrinsic resistance to azole antifun-
`gal drugs [10], such that these reclassified genera now represent
`specific evolutionary traits, the third criterion for a genus
`(Figure 1).
`Analyses of 18S and internal transcribed spacer ribosomal
`DNA (rDNA) have determined that Candida rugosa represents
`a complex of highly similar species, including C rugosa,
`
`2 • OFID • Kidd et al
`
`LCY Biotechnology Holding, Inc.
`Ex. 1039
`Page 2 of 15
`
`

`

`Downloaded from https://academic.oup.com/ofid/article/10/1/ofac559/6974385 by The University of Texas at Austin user on 03 July 2024
`
`Figure 1. Phylogenetic analysis showing the genetic and antifungal susceptibility relationships between 76 Saccharomycotina yeasts within the 14 recognized clades. The
`tree was based on ribosomal DNA data (18S, ITS1, 5.8S, ITS2, and D1/D2) and constructed using maximum likelihood analysis. Species names in bold indicate those com-
`monly reported in a clinical setting. General antifungal susceptibility properties have been indicated on the tree. Reproduced from Stavrou et al, FEMS Yeast Research 19(4):
`foz037 [10], with permission from Oxford University Press.
`
`Fungal Nomenclature • OFID • 3
`
`LCY Biotechnology Holding, Inc.
`Ex. 1039
`Page 3 of 15
`
`

`

`Downloaded from https://academic.oup.com/ofid/article/10/1/ofac559/6974385 by The University of Texas at Austin user on 03 July 2024
`
`Table 1. Summary of Nomenclature Changes in Clinically Important Yeast-like Fungi
`
`Previous Name(s)
`
`Current Name
`
`Commonly Associated Infections
`
`Reference
`
`Candida bracarensis
`Candida catenulata
`Candida colliculosa
`Candida fabianii
`Candida famata
`Candida glabrata
`Candida guilliermondii
`Candida krusei
`Candida kefyr,
`Candida pseudotropicalis
`Candida lipolytica
`Candida lusitaniae
`Candida nivariensis
`Candida neorugosa
`Candida norvegensis
`Candida pararugosa
`Candida pelliculosa,
`Pichia anomala
`Candida pseudorugosa
`Candida rugosa
`Cryptococcus albidus
`Cryptococcus curvatus
`Cryptococcus cyanovorans
`Cryptococcus laurentii
`Pseudozyma antarctica
`Pseudozyma aphidis
`Pseudozyma churashimaensis
`Pseudozyma crassa
`Pseudozyma parantarctica
`Pseudozyma siamensis
`Geotrichum capitatum
`Geotrichum clavatum,
`Saprochaete clavata
`Pichia ohmeri
`Trichosporon cutaneum
`Trichosporon dermatis
`Trichosporon domesticum
`Trichosporon loubieri
`Trichosporon mucoides
`Trichosporon montevideense
`Trichosporon mycotoxinivorans
`
`aSpecies is pending formal description.
`
`Nakaseomyces bracarensisa
`Diutina catenulata
`Torulaspora delbrueckii
`Cyberlindnera fabianii
`Debaryomyces hansenii
`Nakaseomyces glabrataa
`Meyerozyma guilliermondii
`Pichia kudriavzevii
`Kluyveromyces marxianus
`
`Yarrowia lipolytica
`Clavispora lusitaniae
`Nakaseomyces nivariensisa
`Diutina neorugosa
`Pichia norvegensis
`Diutina pararugosa
`Wickerhamomyces anomalus
`
`Diutina pseudorugosa
`Diutina rugosa
`Naganishia albida
`Cutaneotrichosporon curvatus
`Cutaneotrichosporon cyanovorans
`Papiliotrema laurentii
`Moesziomyces antarticus
`Moesziomyces aphidis
`Dirkmeia churashimaensis
`Triodiomyces crassus
`Moesziomyces parantarcticus
`Ustilago siamensis
`Magnusiomyces capitatus
`Magnusiomyces clavatus
`
`Kodamaea ohmeri
`Cutaneotrichosporon cutaneum
`Cutaneotrichosporon dermatis
`Apiotricum domesticum
`Apiotrichum loubieri
`Cutaneotrichosporon mucoides
`Apiotrichum montevideense
`Apiotrichum mycotoxinivorans
`
`Invasive infections including fungemia
`Invasive infections including fungemia
`Invasive infections including fungemia
`Invasive infections including fungemia
`Invasive infections including fungemia
`Invasive infections including fungemia
`Invasive infections including fungemia
`Invasive infections including fungemia
`Invasive infections including fungemia
`
`Invasive infections including fungemia
`Invasive infections including fungemia
`Invasive infections including fungemia
`Invasive infections including fungemia
`Invasive infections including fungemia
`Invasive infections including fungemia
`Invasive infections including fungemia
`
`Invasive infections including fungemia
`Invasive infections including fungemia
`Invasive infections including fungemia
`Invasive infections
`Respiratory infections, especially in cystic fibrosis
`Invasive infections including fungemia
`Fungemia
`Fungemia
`Fungemia
`Fungemia
`Fungemia
`Fungemia
`Invasive infections including fungemia
`Invasive infections including fungemia
`
`Invasive infections including fungemia
`Cutaneous/superficial infections
`Cutaneous infections, allergic conditions
`Uncertain pathogenicity
`Invasive infections including fungemia
`Cutaneous/superficial infections
`Invasive infections including fungemia
`Invasive infections including fungemia
`
`[8]
`[14]
`[16]
`[16]
`[16]
`[8]
`[16]
`[16]
`[16]
`
`[16]
`[16]
`[8]
`[14]
`[16]
`[14]
`[17]
`
`[14]
`[14]
`[18]
`[18]
`[18]
`[18]
`[19]
`[19]
`[19]
`[19]
`[19]
`[19]
`[20]
`[20]
`
`[21]
`[18]
`[18]
`[18]
`[18]
`[18]
`[18]
`[18]
`
`Other clinically relevant Cryptococcus species transferred to oth-
`er genera were Filobasidium magnum (formerly Cryptococcus
`magnus), Naganishia adeliensis (formerly Cryptococcus adeliensis),
`Naganishia albida (formerly Cryptococcus albidus), Naganishia
`diffluens (formerly Cryptococcus diffluens), Naganishia liquefaciens
`(formerly Cryptococcus liquefaciens), and Papiliotrema laurentii
`(formerly Cryptococcus laurentii) [32].
`
`Pseudozyma
`Pseudozyma species, which are closely related to smut fungi
`in the Ustilaginaceae, are emerging as a cause of human
`fungemia. While reported cases are few, most commonly
`
`Pseudozyma aphidis has been identified as the cause of infec-
`tion, but also Pseudozyma antarctica, Pseudozyma parantarcti-
`ca, Pseudozyma alboarmeniaca, Pseudozyma churashimaensis,
`Pseudozyma crassa, Pseudozyma siamensis, and Pseudozyma
`thailandica [36, 37]. This genus has been demonstrated as poly-
`phyletic, with many species clustering with other genera within
`the Ustilaginaceae [19]. Pseudozyma aphidis, P antarctica, and
`P parantarctica clustered with Moesziomyces bullatus and were
`therefore transferred to this genus as Moesziomyces aphidis,
`Moesziomyces antarcticus, and Moesziomyces parantarcticus,
`respectively; a new genus was created for P churashimaensis,
`now known as Dirkmeia churashimaensis; P crassa was
`
`4 • OFID • Kidd et al
`
`LCY Biotechnology Holding, Inc.
`Ex. 1039
`Page 4 of 15
`
`

`

`Downloaded from https://academic.oup.com/ofid/article/10/1/ofac559/6974385 by The University of Texas at Austin user on 03 July 2024
`
`transferred to Triodiomyces as Triodiomyces crassus; P siamen-
`sis was transferred to Ustilago as Ustilago siamensis; and the tax-
`onomic status of P alboarmeniaca and P thailandica remains to
`be resolved [19].
`
`Trichosporon
`Trichosporon was greatly expanded by the addition of novel spe-
`cies prior to the taxonomic revision by Liu and colleagues [18,
`32]. Currently, Trichosporon includes the clinically relevant spe-
`cies Trichosporon asahii, Trichosporon asteroides, Trichosporon
`coremiiforme, Trichosporon dohaense, Trichosporon faecale,
`Trichosporon inkin, Trichosporon japonicum, and Trichosporon
`ovoides [18, 32]. Trichosporon montevideense and Trichosporon
`mycotoxinivorans were
`to Apiotrichum
`transferred
`as
`Apiotrichum montevideense and Apiotrichum mycotoxinivorans,
`respectively. Trichosporon cutaneum, Trichosporon jirovecii,
`Trichosporon dermatis, Trichosporon mucoides, Cryptococcus cur-
`vatus, and Cryptococcus cyanovorans have been accommodated
`in the new genus Cutaneotrichosporon, all retaining their species
`epithets [18].
`
`Geotrichum
`Geotrichum is a genus of arthroconidial yeast-like fungi and an
`emerging cause of fungemia in immunocompromised patients
`[38]. Originally species were assigned based upon morpholog-
`ical differences only but have since undergone extensive taxo-
`nomic revision [38–42]. Examination of 18S rDNA sequences
`discerned 2 major groups, the first containing Geotrichum spe-
`cies with Galactomyces and Dipodascus teleomorphs, and the
`second comprising Saprochaete species with Magnusiomyces
`teleomorphs [39]. Geotrichum clavatum fell into the second
`group and was thus renamed as Saprochaete clavata, whereas
`Geotrichum capitatum was renamed as Magnusiomyces capita-
`tus; more recently a multigene phylogenetic analysis supported
`transferring S clavata to Magnusiomyces as Magnusiomyces
`clavatus [20]. Thus, Geotrichum candidum remains the only
`clinically relevant species in this genus.
`
`HYALINE HYPHOMYCETE MOLDS
`
`Aspergillus
`Aspergillus species, including the 9 teleomorphic genera associ-
`ated with them, are among the most common causes of invasive
`or allergic disease in humans and animals [43, 44], particularly
`the immunosuppressed, in addition to their devastating impact
`on agriculture due to mycotoxin production as well as biodiver-
`sity and ecological health [45, 46]. The application of “one fun-
`gus: one name” to the taxonomy of this group was an area of
`concern, given the potential for many clinically important
`Aspergillus species to be renamed according to their teleo-
`morphs [47, 48]. However, multigene phylogenetic studies
`found that Aspergillus is broadly monophyletic, without
`
`overlapping with its sibling genus Penicillium [49, 50]. The
`monophyly of Aspergillus allowed this name to be maintained
`for most species in the genus, and the clinical importance of
`its name to be preserved. Those species commonly known by
`their teleomorphs were renamed within Aspergillus (eg,
`Neosartorya fischeri was renamed as Aspergillus fischeri).
`Many new Aspergillus species have been described in the past
`2 decades, with molecular studies finding numerous genetically
`distinct species within those which were originally described
`based on their morphological characteristics. At least 50 genet-
`ically distinct species have been identified within the morpho-
`logically circumscribed Aspergillus fumigatus, including the
`pathogenic and antifungal resistant Aspergillus lentulus, A fi-
`scheri, and Aspergillus udagawae [51–53]. Molecular investiga-
`tion of other “morphological species” of Aspergillus have also
`identified “cryptic species” within [54–57]. Table 2 summarizes
`in Aspergillus and other hyaline
`nomenclature changes
`hyphomycetes.
`
`Penicillium
`A 2011 multigene analysis of Penicillium and Talaromyces spe-
`cies found the Biverticillium subgenus of the former to be
`monophyletic with the latter; thus, species in the subgenus
`Biverticillium group were transferred to Talaromyces [67].
`This included the clinically important Talaromyces marneffei,
`species of Penicillum/
`the only
`thermally dimorphic
`Talaromyces, which is endemic to tropical areas of Southeast
`and South Asian countries, predominantly seen as systemic in-
`fection in human immunodeficiency virus (HIV)–positive in-
`dividuals [70]. The red diffusible pigment released into
`semi-solid media is regarded as a typical T marneffei pheno-
`type; however, several Talaromyces species exhibit this pheno-
`type, including Talaromyces atroroseus and Talaromyces
`purpureogenus, both described as industrially relevant pigment
`producers [71, 72]. Both species have been reported as the cause
`of infection in patients with and without HIV, or with other un-
`derlying conditions [73–76].
`
`Paecilomyces
`Paecilomyces, a genus of cosmopolitan fungi largely known for
`their biological control applications against bacteria, phyto-
`pathogenic fungi, and nematodes [77], are occasional causes
`of keratitis and onychomycosis, as well as hyalohyphomycosis
`in immunocompromised patients [78]. A multilocus phyloge-
`netic study of Paecilomyces found significant variation [65],
`and the major pathogenic species Paecilomyces variotii,
`Paecilomyces lilacinus, and Paecilomyces marquandii were
`each
`found
`to group with different
`families
`(the
`Trichocomaceae, Ophiocordycipitaceae, and Clavicipitaceae,
`respectively). On this basis, P lilacinus and P marquandii
`were each transferred to a new genus as Purpureocillium lilaci-
`num and Marquandomyces marquandii, respectively [65, 66].
`
`Fungal Nomenclature • OFID • 5
`
`LCY Biotechnology Holding, Inc.
`Ex. 1039
`Page 5 of 15
`
`

`

`Downloaded from https://academic.oup.com/ofid/article/10/1/ofac559/6974385 by The University of Texas at Austin user on 03 July 2024
`
`Table 2. Summary of Nomenclature Changes in Clinically Important Hyaline Hyphomycete Molds
`
`Previous Name(s)
`
`Current Name
`
`Commonly Associated Infections
`
`Reference
`
`Acremonium kiliense
`Acremonium roseogriseum
`Acremonium strictum
`Arthroderma benhamiae
`Cerinosterus cyanescens,
`Sporothrix cyanescens
`Fusarium dimerum
`Fusarium falciforme,
`Acremonium falciforme
`Fusarium keratoplasticum
`Fusarium lichenicola
`Fusarium petroliphilum
`Fusarium solani
`Geosmithia argillacea,
`Penicillium argillaceum
`Gibberella fujikuroi
`Lecythophora hoffmannii,
`Phialophora hoffmannii
`Microsporum cookei
`Microsporum fulvum
`Microsporum gallinae
`Microsporum gypseum
`Microsporum nanum
`Microsporum persicolor
`Neosartorya fischeri,
`Neosartorya pseudofischeri,
`Aspergillus thermomutatus
`Neosartorya udagawae
`Paecilomyces lilacinus
`Paecilomyces marquandii
`Penicillium marneffei
`Penicillium purpureogenum
`Trichophyton terrestre
`Trichophyton ajelloi
`Trichophyton mentagrophytes
`var interdigitale
`var mentagrophytes
`genotype VIII
`
`Sarocladium kiliense
`Gliomastix roseogrisea
`Sarocladium strictum
`Trichophyton benhamiae
`Quambalaria cyanescens
`
`Fungemia, subcutaneous infections
`Not associated with infection
`Cutaneous, invasive infections
`Cutaneous infections
`Peritonitis, pneumonia, postsurgical complications
`
`Bisifusarium dimerum
`Neocosmospora falciformis
`
`Keratitis, invasive infections
`Keratitis, invasive infections
`
`Neocosmospora keratoplastica
`Neocosmospora lichenicola
`Neocosmospora petroliphila
`Neocosmospora solani
`Rasamsonia argillacea
`
`Keratitis, invasive infections
`Keratitis, invasive infections
`Keratitis, invasive infections
`Keratitis, invasive infections
`Respiratory infections, especially in cystic fibrosis
`
`Fusarium fujikuroi
`Coniochaeta hoffmannii
`
`Keratitis, invasive infections
`Subcutaneous infections
`
`Paraphyton cookei
`Nannizzia fulva
`Lophophyton gallinae
`Nannizzia gypsea
`Nannizzia nana
`Nannizzia persicolor
`Aspergillus fischeri
`
`Aspergillus udagawae
`Purpureocillium lilacinum
`Marquandomyces marquandii
`Talaromyces marneffei
`Talaromyces purpureogenus
`Arthroderma terrestre
`Arthroderma uncinatum
`
`Cutaneous infections
`Cutaneous infections
`Cutaneous infections
`Cutaneous infections
`Cutaneous infections
`Cutaneous infections
`Respiratory, invasive infections, allergic conditions
`
`Respiratory, invasive infections, allergic conditions
`Keratitis, cutaneous infections
`Cutaneous infections (rare)
`Systemic infections
`Pulmonary infections (rare)
`Doubtful pathogenicity
`Cutaneous infections
`
`Trichophyton interdigitale
`Trichophyton mentagrophytes
`Trichophyton indotineae
`
`Cutaneous infections
`Cutaneous infections
`Cutaneous infections
`
`[58]
`[58]
`[58]
`[59]
`[60]
`
`[61]
`[61]
`
`[61]
`[61]
`[61]
`[61]
`[62]
`
`[63]
`[64]
`
`[59]
`[59]
`[59]
`[59]
`[59]
`[59]
`[50]
`
`[50]
`[65]
`[66]
`[67]
`[67]
`[59]
`[59]
`
`[68]
`[68]
`[69]
`
`Rasamsonia
`Rasamsonia argillacea, often recovered from the airways of pa-
`tients with cystic fibrosis [79], and a cause of disseminated in-
`fections in those with chronic granulomatous disease and
`immunosuppression [80], bears morphological similarities to
`Penicillium and Paecilomyces species. Originally classified as
`Penicillium argillaceum and noted for its thermotolerance, it
`in 1979, Geosmithia
`was transferred to a new genus
`(as Geosmithia argillacea) with teleomorph Talaromyces
`eburneus [81]. Geosmithia was later found to be polyphyletic
`[82], paving the way to the eventual creation of a new genus
`of thermotolerant pathogens, Rasamsonia, for Rasamsonia
`argillacea, Rasamsonia aegroticola, Rasamsonia eburnea, and
`Rasamsonia piperina, often referred to as the R argillacea com-
`plex [62, 83].
`
`Fusarium and Fusarioid Genera
`Modern taxonomy of Fusarium and related genera is based on
`multilocus phylogenies, accompanied by genomic data, mor-
`phological descriptions, and physiological and ecological
`data. This caused a significant but necessary revision in classi-
`fication and nomenclature of these fungi. Fusarium and allied
`fusarioid genera, Bisifusarium (formerly the Fusarium dime-
`rum species complex), and Neocosmospora (formerly the
`Fusarium solani species complex), contain a genetically diverse
`group of hyaline fungi with global distribution. They are mainly
`known as ubiquitous soil saprobes, plant pathogens, and myco-
`toxin producers; however invasive human infections in immu-
`nocompromised patients have high mortality despite
`antifungal therapy. They are also major causes of fungal kera-
`titis and nondermatophyte onychomycosis. Application of
`
`6 • OFID • Kidd et al
`
`LCY Biotechnology Holding, Inc.
`Ex. 1039
`Page 6 of 15
`
`

`

`Downloaded from https://academic.oup.com/ofid/article/10/1/ofac559/6974385 by The University of Texas at Austin user on 03 July 2024
`
`phylogenetic species recognition revealed that there are nearly
`500 species in Fusarium. Members of Fusarium species com-
`plexes are different in morphology, host association, and mo-
`lecular characteristics [63] (www.fusarium.org). The majority
`of human infections are caused by the F solani species complex
`(FSSC), which contains numerous phylogenetically distinct
`species. New formal names within Neocosmospora have been
`proposed for several F solani lineages [61]. The most common-
`ly reported species, under recent revised nomenclature,
`to Neocosmospora keratoplastica
`correspond
`(formerly
`Fusarium keratoplasticum [FSSC2]), Neocosmospora petroliphi-
`la (formerly Fusarium petroliphilum [FSSC1]), Neocosmospora
`falciformis
`(formerly Fusarium
`falciforme
`[FSSC3 + 4]),
`Neocosmospora lichenicola (formerly Fusarium lichenicola),
`and Neocosmospora
`solani
`(formerly Fusarium
`solani
`[FSSC5]). Notably, morphological species recognition is unable
`to distinguish Fusarium-like taxa that have been described
`based on genealogical concordance of phylogenetic species rec-
`ognition. Thus, the term “fusarioid” was suggested when phe-
`notypic methods are solely used to identify Fusarium-like
`members of Nectriaceae. Accurate species-level identification
`of Fusarium and related genera from clinical specimens re-
`quires multigene sequencing with comparison to well-curated
`databases, which is often beyond the capacity of routine diag-
`nostic mycology laboratories. Thus, there is currently no stan-
`dard approach in reporting of these fungi in clinical practice.
`
`Dermatophytes
`Dermatophytes, a group of keratinophilic hyaline hyphomy-
`cetes, have traditionally been classified within 3 asexual genera
`Trichophyton, Microsporum, and Epidermophyton, whereas
`species with sexual reproduction were placed in within
`Arthroderma and Nannizzia. While this morphological classifi-
`cation is useful in dermatology clinics and routine diagnostic
`mycology
`laboratories,
`it does not capture
`the
`true
`diversity of this group. A recent multilocus phylogenetic
`analysis of type and reference strains [59] showed that
`Trichophyton
`is polyphyletic and proposed a generic
`classification scheme for all dermatophytes containing 7
`genera—namely, Trichophyton, Epidermophyton, Nannizzia,
`Microsporum, Lophophyton, Paraphyton, and Arthroderma.
`Most of the anthropophilic and some zoophilic species re-
`mained in 3 older groups of Trichophyton, Microsporum, and
`Epidermophyton. In contrast, geophilic and some rare zoophilic
`dermatophytes are now classified in the remaining 4 genera
`(summarized in Table 2). Under this new scheme, novel geo-
`philic species such as Arthroderma eboreum and Nannizzia
`aenigmatica have been described. Some older names used to
`describe distinct phenotypic variants of dermatophytes are no
`longer in use (eg, Trichophyton megninii, Trichophyton gourvi-
`lii, Trichophyton yaoundei, Microsporum boullardii, and
`Microsporum equinum).
`
`Recent additions to the revised classification include 3 novel
`species causing tinea corporis, Arthroderma chiloniense [84],
`Nannizzia perplicata [85], and Trichophyton indotineae [69],
`the latter being of major clinical significance. Trichophyton in-
`dotineae exhibits a high level of terbinafine resistance due to
`missense mutations is the squalene epoxidase gene, causing ex-
`tensive recalcitrant infections, mainly in the Indian subconti-
`nent [86], but also reported from Europe [87] and Canada [88].
`
`THERMALLY DIMORPHIC FUNGI
`
`fungal genera Blastomyces,
`thermally dimorphic
`The
`Emergomyces, Histoplasma, Paracoccidioides, and Sporothrix
`have all significant taxonomic changes. The exception is the ge-
`nus Coccidioides that 2 decades ago was expanded from a single
`to 2 species, Coccidioides
`immitis and
`representative
`Coccidioides posadasii, and has been stable ever since [89].
`Changes and additions for the other genera are described below
`and summarized in Table 3.
`
`Histoplasma
`Histoplasma capsulatum was until recently represented by 3 va-
`rieties: H capsulatum var capsulatum, var duboisii, and var far-
`cimi