COMMENTARY
`
`Name Changes in Medically Important Fungi and Their Implications
`for Clinical Practice
`
`G. Sybren de Hoog,a Vishnu Chaturvedi,b David W. Denning,c Paul S. Dyer,d Jens Christian Frisvad,e David Geiser,f Yvonne Gräser,g
`Josep Guarro,h Gerhard Haase,i Kyung-Joo Kwon-Chung,j
`Jacques F. Meis,k Wieland Meyer,l John I. Pitt,m Robert A. Samson,n
`John W. Taylor,o Kathrin Tintelnot,p Roxana G. Vitale,q Thomas J. Walsh,r Michaela Lackner,s the ISHAM Working Group on
`Nomenclature of Medical Fungi
`CBS-KNAW Fungal Biodiversity Centre, Utrecht, The Netherlands, Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, Amsterdam, The
`Netherlands, Peking University Health Science Center, Research Center for Medical Mycology, Beijing, China, Sun Yat-sen Hospital, Sun Yat-sen University, Guangzhou,
`China, Shanghai Institute of Medical Mycology, Changzheng Hospital, Second Military Medical University, Shanghai, China, Basic Pathology Department, Federal
`University of Paraná State, Curitiba, Paraná, Brazil, and King Abdulaziz University, Jeddah, Saudi Arabiaa; Mycology Laboratory, Wadsworth Center, New York State
`Department of Health, Albany, New York, USAb; Education and Research Centre, University Hospital of South Manchester, Manchester, United Kingdomc; School of Life
`Sciences, The University of Nottingham, Nottingham, United Kingdomd; Center for Microbial Biotechnology, Department of Systems Biology-DTU, Technical University of
`Denmark, Lyngby, Denmarke; Department of Plant Pathology, Pennsylvania State University, State College, Pennsylvania, USAf; Institute for Microbiology and Hygiene,
`University Hospital Charité, Berlin, Germanyg; Mycology Unit, Medical School and IISPV, Universitat Rovira i Virgili, Reus, Spainh; Institute of Medical Microbiology and DLZ,
`RWTH Aachen University Hospital, Aachen, Germanyi; Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and
`Infectious Diseases, NIH, Bethesda, Maryland, USAj; Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, and Department of
`Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlandsk; Molecular Mycology Research Laboratory, CIDM, Sydney Medical School-
`Westmead Hospital, University of Sydney, Sydney, Australial; Food Science Australia, North Ryde, NSW, Australiam; CBS-KNAW Fungal Biodiversity Centre, Utrecht, The
`Netherlands, Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, Amsterdam, The Netherlandsn; Fungal Evolution and Genomics, Plant and
`Microbial Biology, University of California, Berkeley, Berkeley, California, USAo; Robert Koch Institute, Berlin, Germanyp; Departamento de Micologia, CONICET, and Hospital
`JM Ramos Mejía, Buenos Aires, Argentinaq; Mycology Research Laboratory, Weill Cornell University Medical Center, New York, New York, USAr; Division of Hygiene and
`Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austrias
`
`Recent changes in the Fungal Code of Nomenclature and developments in molecular phylogeny are about to lead to dramatic
`changes in the naming of medically important molds and yeasts. In this article, we present a widely supported and simple pro-
`posal to prevent unnecessary nomenclatural instability.
`
`ONE FUNGUS, ONE NAME
`
`Until recently, polymorphic higher fungi (Dikarya) were allowed
`
`to carry multiple names describing sexual (teleomorph) and
`various asexual (anamorph) stages of their life cycles. These stages
`could develop independently from each other, and their genetic
`relationship was often difficult to establish. Today, with the wide
`application of molecular methods, this problem has largely been
`solved. With the introduction of molecular genetic approaches,
`the dual naming system is no longer necessary. Two international
`expert symposia recently held in Amsterdam, The Netherlands,
`have been devoted to the fate of dual naming in fungi: One Fun-
`gus ⫽ One Name symposium on 19 and 20 April 2011 and One
`Fungus ⫽ Which Name symposium on 12 and 13 April 2012. The
`resulting Amsterdam Declaration on Fungal Nomenclature (1)
`requested the abolition of Article 59 of the Code of Botanical No-
`menclature, the provision that sanctioned multiple names for the
`same fungus. Under the new Code of Nomenclature of Algae,
`Fungi and Plants, from 1 January 2013, this system is no longer
`permitted. One of the consequences of the declaration is that the
`criteria for naming fungi have changed entirely.
`The dual naming system had been useful during the age of the
`microscope. Today, the main criteria for classification have moved
`from phenotype to genotype. Analysis of nucleic acid sequence vari-
`ation now guides taxonomy and has replaced phenotype with the
`history of phylogenetic relationships and, occasionally, sexual com-
`patibility. The first phase began after the introduction of PCR in the
`late 1980s and resulted in the discovery of new species by concor-
`dance of gene genealogies in several pathogenic fungi. This is now
`
`being expanded following the advent of next-generation sequencing,
`which is discovering genetically distinct populations that deserve spe-
`cies status. The newly discovered species are genealogically distinct
`but cryptic in the sense that they were not suspected from morpho-
`logical phenotype—although after they are recognized, distinguish-
`ing phenotypes may be discovered later on. In addition, taxonomy of
`environmental fungi is developing at a very rapid pace, which has a
`profound impact on nomenclature of opportunistic fungi. Anatomic
`morphological categories, such as coelomycetes or hyphomycetes,
`have become redundant, which implies that all mycological text-
`books have become obsolete. Diagnostic laboratories will have to
`change the type and interpretation of data used to identify fungi. The
`changes will hopefully contribute to nomenclatural stability in the
`
`Accepted manuscript posted online 8 October 2014
`Citation de Hoog GS, Chaturvedi V, Denning DW, Dyer PS, Frisvad JC, Geiser D,
`Gräser Y, Guarro J, Haase G, Kwon-Chung K-J, Meis JF, Meyer W, Pitt JI, Samson RA,
`Taylor JW, Tintelnot K, Vitale RG, Walsh TJ, Lackner M, the ISHAM Working Group
`on Nomenclature of Medical Fungi. 2015. Name changes in medically important
`fungi and their implications for clinical practice. J Clin Microbiol 53:1056 –1062.
`doi:10.1128/JCM.02016-14.
`Editor: D. W. Warnock
`Address correspondence to Michaela Lackner, Michaela.Lackner@i-med.ac.at, or
`John W. Taylor, jtaylor@berkeley.edu.
`Copyright © 2015, American Society for Microbiology. All Rights Reserved.
`doi:10.1128/JCM.02016-14
`The views expressed in this Commentary do not necessarily reflect the views of the
`journal or of ASM.
`
`1056 jcm.asm.org
`
`Journal of Clinical Microbiology
`
`April 2015 Volume 53 Number 4
`
`LCY Biotechnology Holding, Inc.
`Ex. 1027
`Page 1 of 7
`
`

`

`future, but it is obvious that this will not be achieved before the end of
`a transition phase. Although the shift in identification can be viewed
`as simply a change in technique from microscopy to DNA sequence
`analysis, it must also be viewed as a major intellectual shift to a system
`based on evolution as inferred from comparison of genotypes.
`Coincidently with this process, a significant expansion of the
`number of etiologic agents of disease is noticed. In the literature, it
`is often stated that (i) this growth is especially due to the increasing
`population of immunocompromised patients. A more pertinent
`cause, however, is (ii) the development of our knowledge, driven
`by easy access to sequencing technology. The advent of population
`genomics, which increases the sampled diversity by as many as 4
`orders of magnitude, can only increase this trend. A further source
`of new clinical species to be recognized in diagnostic laboratories
`is the fact that (iii) also sterile or nonculturable fungi can now be
`classified according to sequence analysis of PCR-generated ampli-
`cons. The expansion of the number of clinically relevant fungi is
`clearly demonstrated in the Atlas of Clinical Fungi of which the
`first edition (2) contained 320 species, while the 2013 edition of
`the same book (3) counts a staggering 560 species, and the number
`of species is still growing at the same pace.
`When only a single name should be used for these fungi, most
`of which bear several names at present, the question is which name
`has priority? One of the principles of nomenclature is to choose (i)
`the oldest name, either anamorph or teleomorph, which is also
`mostly the most widely applied name. The new code has the sec-
`ond rule that if both anamorph and teleomorph names have been
`widely used, (ii) the teleomorph name is to be maintained unless a
`formal application in favor of the anamorph name has been made.
`Both choices are dependent on (iii) the size of the genus and its
`rank in the taxonomic hierarchy.
`
`CHANGES AT THE GENUS LEVEL AND ABOVE
`
`Starting with item iii, genus concepts are related to the amount
`and diversity of available biological material. Nucleic acid varia-
`tion has provided a means of ensuring that genera are monophy-
`letic, which is a leading principle of modern taxonomy. Species
`differing at the ordinal or even family level are no longer accepted
`as members of a single genus. Hence, orders and sometimes fam-
`ilies are taxonomically relevant entities. The advantage of the phy-
`logenetic approach is that close relatives come together even if
`they are morphologically quite different; this may be useful for
`predictions of pathogenicity or antifungal susceptibility. Con-
`versely, distant relationships are expected to predict large differ-
`ences in clinically relevant parameters. Until today, most clinical
`fungi had been grouped in anamorphic form genera based on
`phenotype that do not necessarily represent phylogenetic related-
`ness. For example, non-albicans Candida species comprise a ran-
`dom mixture of species that have been grouped together only
`because they are morphologically indistinguishable and physio-
`logically similar, but some of them are as distant from each other
`as humans are from frogs. Applying names that acknowledge this
`diversity would be logical and medically meaningful. Candida al-
`bicans and Candida glabrata are evolutionary distant species with
`different antifungal susceptibilities (4). Penicillium marneffei is
`unrelated to most of the saprobic Penicillium species, but it be-
`longs to a group of penicillium-like species classified in the genus
`Talaromyces that possess similar virulence factors. Therefore, re-
`classification of P. marneffei in Talaromyces (5) is useful for the
`medical mycologist. Similar reasoning can be applied to categories
`
`Commentary
`
`higher up in the fungal system. Although the Zygomycota appears
`not to be monophyletic, there has been reluctance to abandon the
`name, but as the diseases caused by the main groups composing it,
`the Mucoromycotina and Entomophthoromycotina, are funda-
`mentally different (6), their separation would be a step forward.
`The novel approach using phylogeny as a main criterion enhances
`information content of the taxonomy hierarchy.
`The above is valid on the assumption that the “real” phyloge-
`netic tree of the fungal kingdom is known. However, it should be
`realized that only a minor fraction of the existing fungal diversity
`has been described thus far. Large numbers of novel species are
`continuously being discovered due to the exploration of new hab-
`itats. The main cause of generic instability is material driven; phy-
`logenetic trees are highly sensitive to taxon sampling effects (Fig.
`1), and this situation will remain for many decades to come. De-
`scription of species on the basis of single sequences from metag-
`enomic data will further complicate the taxonomic system (7).
`The basis of a genus or of any higher rank in the taxonomic hierarchy
`is a monophyletic branch of an underlying phylogenetic tree, replac-
`ing phenotypic techniques. Fungi may appear to belong to other phy-
`logenetic groups than hypothesized earlier.
`The clade approach for naming species, genera, and above has
`fundamental shortcomings, because of the comparative nature of
`data and also because no delimitation criterion exists. Determina-
`tion of all higher taxonomic ranks when they are defined exclu-
`sively by sequence data is inherently arbitrary and therefore un-
`stable, leading to numerous transfers of species from one genus
`to the next. Phylogeny deepens our understanding of the fungal
`kingdom, but phylogenetic trees are just an approximation of the
`truth. During the last 10 years, more name changes have been
`proposed for medical fungi than in the previous 70 years; exam-
`ples can be found in Table 1. Many clades in a tree can be statisti-
`cally supported, but what is the level of diversity to recognize a
`genus? At present, Aspergillus contains about 290 species, while
`genera in the Scedosporium lineage, with comparable levels of bar
`coding gaps between neighboring taxa, contain only 1 to 6 species.
`If genera become nearly congruent to species, then the genus be-
`comes a redundant category.
`A profoundly debated example is the anamorph genus Asper-
`gillus. The Aspergillus genus was discovered by Micheli in 1753,
`based on Aspergillus glaucus. However, the medically important
`fungus Aspergillus fumigatus is a member of another phylogenetic
`clade in Aspergillus that also bears the teleomorph name Neosar-
`torya. In the case of A. fumigatus, which was found to have a
`Neosartorya sexual state in 2009 after a concerted effort to generate
`ascocarps (8), the anamorph name A. fumigatus is older and more
`widely used than N. fumigata. However, the A. fumigatus/N. fumi-
`gata clade is phylogenetically remote and phenotypically distinct
`from the clade that contains the generic type, A. glaucus (9). There
`are two proposals in the literature. One advocates making Asper-
`gillus a very large genus covering numerous clades, including
`those of A. glaucus and A. fumigatus (9). After careful discussion
`among the members, this proposal was chosen by the Interna-
`tional Commission of Penicillium and Aspergillus. The other ad-
`vocates applying existing teleomorph names to all monophyletic
`branches except one, and that clade alone would retain the name
`Aspergillus (10).
`Both proposals have their pros and cons. In the first case,
`Aspergillus would remain the name for all, but as the broad phy-
`logeny includes genera such as Phialosimplex and Polypaecilium
`
`April 2015 Volume 53 Number 4
`
`Journal of Clinical Microbiology
`
`jcm.asm.org 1057
`
`LCY Biotechnology Holding, Inc.
`Ex. 1027
`Page 2 of 7
`
`

`

`Commentary
`
`FIG 1 Diagram of name changes driven by methodical advances and sampling effects: subdivisions, reallocations, and rank inflations.
`
`would have to be renamed in Aspergillus. The breadth of pheno-
`type embraced by Aspergillus would include fungi that have never
`been associated with Aspergillus, but the phylogenetic data sup-
`porting this are solid (11), and it should be acknowledged that
`aspergilli with deviating morphological features do exist. In the
`second case, A. fumigatus would be named Neosartorya fumigata
`because Neosartorya species form a distinct monophyletic clade
`within the exiting genus Aspergillus. This may be unpleasant for
`medical mycologists, but for many other users of the fungal king-
`dom, this is good news as Aspergillus would then be used to refer
`specifically to Aspergillus species in the subgenus Circumdati.
`These include fungi with even more prominent economic value,
`for example the Asian food fungus, Aspergillus oryzae, its close
`relative, the aflatoxin producer, Aspergillus flavus, and the indus-
`trial fermentation workhorse, Aspergillus niger.
`In summary, a major source of potential name changes, in
`addition to problems of dual nomenclature, is linked to phylogeny
`as a leading principle, while phylogenetic trees and taxonomic
`hierarchies are still under construction and subject to change
`while nature’s diversity is better understood.
`
`CHANGES AT THE SPECIES LEVEL AND BELOW
`
`Species recognition is primarily method driven, i.e., tied to the
`method of observation. The shift from recognizing species by ob-
`servable phenotype to recognizing them by nucleic acid variation
`has resulted in a proliferation in the number of species. In recent
`
`years, more precision has been achieved in molecular methods by
`replacing species recognition in single-gene studies by multiple-
`gene analysis of lineages and populations, leading to molecularly
`defined taxa (sibling or cryptic species; Table 2). This trend will
`continue now that whole genomes are becoming available for
`large numbers of strains within a single species, as has been shown
`with model fungi (12–14).
`When this process is clinically relevant, the novel naming sys-
`tem should rapidly be adopted. For example, Sporothrix schenckii,
`agent of human sporotrichosis, contains a hypervirulent sibling
`now known as Sporothrix brasiliensis causing large epidemics in
`Brazil (15). In another example, Scedosporium aurantiacum, one
`of the novel species recognized within the former umbrella species
`Scedosporium apiospermum is significantly less susceptible to cur-
`rently used antifungal agents than the original species (16).
`Application of more-variable genes to the same fungi will al-
`ways lead to discovery of more diversity, again as demonstrated by
`population genomics. Almost all fungal species that have been
`examined show evidence of recombination and, therefore, exhibit
`upper and lower bounds to species recognition. The lower bound
`has been found using population genomic analysis to identify ge-
`netically differentiated populations of interbreeding individuals,
`and development of the upper bound has been observed where
`species have evolved reinforced barriers to mating in some areas of
`sympatry and not others (17). Only in clonal species would these
`bounds not apply and entities can be subdivided ad infinitum. In
`
`1058 jcm.asm.org
`
`Journal of Clinical Microbiology
`
`April 2015 Volume 53 Number 4
`
`LCY Biotechnology Holding, Inc.
`Ex. 1027
`Page 3 of 7
`
`

`

`TABLE 1 Some examples of medically important fungi that have undergone recent multiple changes, with year of publication and reasons for
`rearrangement
`
`Original name in medicine
`
`Transitional name(s)
`
`Hendersonula toruloidea 1933
`
`Scytalidium hyalinum 1977 (supposed synonymy)
`
`Current name
`
`Neoscytalidium dimidiatum 2006
`(phylogenetic rearrangement)
`
`Commentary
`
`Scytalidium dimidiatum 1989 (earlier synonym Torula dimidiata 1887)
`Nattrassia mangiferae 1989 (supposed identity of coelomycete anamorph)
`Fusicoccum dimidiatum (2005) (phylogenetic rearrangement)
`Neofusicoccum mangiferae 2006 (phylogenetic rearrangement)
`Neoscytalidium hyalinum 2013 (phylogenetic rearrangement)
`
`Trichosporon capitatum 1942
`
`Geotrichum capitatum 1977 (phylogenetic rearrangement)
`
`Blastoschizomyces capitatus 1985 (synanamorph genus)
`
`Saprochaete capitata 2004 (phylogenetic
`rearrangement of anamorph)
`Magnusiomyces capitatus 2004
`(phylogenetic rearrangement of
`teleomorph; priority of either genus
`name still to be established)
`
`Blastoschizomyces pseudotrichosporon 1982 (synonymy)
`Dipodascus capitatum 1996 (description of teleomorph)
`
`Candida utilis 1952
`
`Hansenula jadinii 1979 (conspecificity with Candida utilis, description of
`teleomorph)
`Pichia jadinii 1984 (phylogenetic rearrangement)
`Lindnera jadinii 2008 (phylogenetic rearrangement)
`
`Cyberlindnera jadinii 2009
`(nomenclatural correction)
`
`Allescheria boydii 1922
`
`Pseudallescheria boydii (teleomorph)
`
`Cephalosporium boydii 1922
`Dendrostilbella boydii 1922
`(anatomic names for a
`trimorphic fungus)
`
`Scedosporium boydii (prevalent anamorph; name for third morph neglected)
`
`Scedosporium boydii (consensus chosen
`by Scedosporium community, but
`Pseudallescheria teleomorph genus
`name has been prioritized by
`nomenclatural community)
`
`practice, many, perhaps most, fungal lineages combine enough
`recombination with clonal behavior to be constrained by both
`upper and lower species boundaries. There is no gold standard as
`a measure of taxonomic diversity at the species level, and thus
`optimal barcoding genes are differentially effective between dif-
`ferent groups.
`Differences between molecular siblings may not always have
`clinical relevance. Distinction of cryptic species may then be tax-
`onomically valid and scientifically meaningful but remain unde-
`tectable in routine laboratory analyses. On a global scale of daily
`
`clinical diagnostics, attempting to detect these species would re-
`quire an investment that would not contribute to patient care and
`is therefore not recommended until further research provides jus-
`tification of these additional efforts. For example, Aspergillus niger
`was recently found (18) to contain a molecular sibling, Aspergillus
`awamori. Varga et al. (19) explicitly mention that there are no
`differences in phenotypic characteristics, such as metabolite pro-
`files between the two, and clinical differences between the two
`species have yet to be discovered. As difficult as it might be to
`distinguish two species, imagine the case of the ubiquitous con-
`
`TABLE 2 Some taxonomic definitions appropriate for medical mycology that are used in the present paper
`
`Term
`
`Species complex
`Sibling species
`Cryptic species
`
`(Sub)clade/monophyletic group
`
`Lineage
`Cluster/group
`Type
`
`Neotype
`Epitype
`Protologue
`
`Taxonomic definition
`
`A monophyletic clade of species with equivalent clinical relevance
`Species that share the same, most recent common ancestor
`Species recognized by nucleic acid variation that had not been recognized as distinct by morphological phenotypes.
`Once recognized, phenotypic characters useful for identification may be discovered in the future.
`Phylogenetic group consisting of an ancestral species and all its descendants. Clades and subclades can be
`recognized at any given taxonomic level. Statistical tests are used to gauge the support for these groups.
`Series of species connected by evolutionary descent, not necessarily representing all known descendants
`Terminal series of phylogenetically related species, used when precise relationships are uncertain.
`Entity defining a taxonomic name and indicated as such in the protologue. Species and below are defined by a
`specimen, whereas higher taxonomic entities are defined by the first lower category.
`New specimen in accordance with the protologue in case the original type material is lost.
`Reference specimen accordance with the protologue when the original material is not interpretable.
`Original description and any other representation of a taxonomic entity.
`
`April 2015 Volume 53 Number 4
`
`Journal of Clinical Microbiology
`
`jcm.asm.org 1059
`
`LCY Biotechnology Holding, Inc.
`Ex. 1027
`Page 4 of 7
`
`

`

`Commentary
`
`taminant Cladosporium cladosporioides, which today contains 39
`cryptic species (20), 38 of which have never been proven as agents
`of human infection.
`Neighboring siblings that are identical in patient management
`and normally characterized phenotype might in routine diagnos-
`tics better be taken together as “complexes.” A “species complex”
`of medically important fungi would be considered a cluster of
`cryptic species that are clinically identical. This is the current in-
`dication of series of closely related Fusarium species (21), and
`similar approaches have been adopted for Cladosporium (20) and
`elsewhere. The word “complex” has no nomenclatural status
`and does not require any name change. Species complexes can
`nevertheless be sharply delimited and validated by molecular data.
`Diagnostic markers can be developed for the molecular siblings
`and for the species complex. If an author wishes to describe other,
`less clearly defined species diversities, terms like “group,” “clus-
`ter,” “lineage,” and “clade” are available (Table 2).
`In summary, a major source of name changes at the species level is
`increased precision of molecular techniques; this nomenclatural in-
`stability is thus largely method driven. The distinguished entities,
`even when scientifically correct and meaningful, may not always have
`clinical relevance, although this significance may perhaps be discov-
`ered in the future.
`
`CONCLUSIONS AND PROPOSALS
`
`During the process of naming each fungus, teleomorph and ana-
`morph names as well as their synonyms are being considered in a
`way that would increase acceptance and stability. Even strict no-
`menclatural rules provide a certain degree of liberty. Many of the
`classical medical fungi and many of their synonyms were de-
`scribed a long time ago, and type material is often lacking or un-
`interpretable. The present paper does not argue for one solution
`or the other in any of the examples above but simply notes that
`there is more than one way to apply one name for one fungus.
`Nomenclatural changes of medically important fungi usually take
`decades to gain wide acceptance. Any change may be viewed as a
`process taking place in the community, rather than as a singular
`result of a phylogenetic study. Taxonomy is a dynamic science,
`which cannot be muzzled by nomenclatural protocols. Realloca-
`tions, rank changes, and generic disarticulations or reunifications
`will remain common practice. Theoretically, the taxonomic sys-
`tem should reflect the true phylogeny of the fungal kingdom, but
`obviously we have not yet reached that stage. Additional data and
`techniques improving the system are continually generated and
`published. Therefore, it may be more prudent to wait until a larger
`degree of stability and consensus is achieved. Many names of op-
`portunistic fungi are published as part of studies on environmen-
`tal fungi, where genera might comprise dozens or hundreds of
`species. The genus name is linked to its type species, and if this
`species appears to be different from all the others, all remaining
`names need to be recategorized in another genus. The result is that
`the number of name changes can be tremendous—a compelling
`reason to be careful with reallocations where scientific support is
`still fragmentary.
`How should the field of medical mycology treat the new diver-
`sity seen in the taxonomy of medically important fungi? At the
`genus level, these are reallocations, rank changes, and generic dis-
`articulations or reunifications that stem from studies of more ma-
`terials and from having to choose one name from two or more
`current names. Where examination of new materials suggests new
`
`names, we urge taxonomists to delay introduction of new names
`until they have sampled sufficient material. Where name change
`results from having to choose one of several names, maintaining
`taxa that have similar medical attributes would serve medical my-
`cology; such taxa should neither be so big as to hide medically
`important phenotypic variation nor so small to lessen the distinc-
`tion between genera and species. Where the names of medically
`important fungi do change—and many will change as the new
`code is applied—it may reflect the fact that medical mycology is
`just one of many socially important activities that focus on fungi.
`Good taxonomic studies do not always need new names immedi-
`ately. For clinical routine, it is advocated to follow changes with
`some delay, after validation by a convincing body of data, until a
`sufficient degree of stability and consensus is reached.
`At the species level, most changes concern subdivisions of clas-
`sical phenotypic species, as new methods allow mycologists to
`examine more and more of the genetic variation, including the
`entire genomes of populations of fungi. As new research tech-
`niques become widespread in clinics, clinicians also will be able to
`recognize more species. Until, after clinical evaluation, newly dis-
`covered species prove to be different in terms of patient manage-
`ment, in daily clinical routine, it might be better to unite such
`siblings as “species complexes.”
`Researchers and clinicians should work together to achieve a
`reasonable degree of nomenclatural stability during the decades
`when large changes are unavoidable. Even when a disease caused
`by two or more closely related species is treated by the same ther-
`apy, insights into diversity of the species may advance medicine by
`allowing clinicians to use this knowledge to discover previously
`overlooked and consistent differences. Specialized websites are
`available where diagnostic materials are provided as an aid for
`identification and the best current taxonomy is available as mat-
`ters change.
`
`ACKNOWLEDGMENTS
`
`The contents of this paper have been communicated to the Nomenclature
`Committee for Fungi (NCF) (www.ima-mycology.org/CFF): S. A. Red-
`head, L. Norvell, and P. Kirk, and the International Commission on the
`Taxonomy of Fungi (ICTF): K. A. Seifert and A. Miller.
`The members of the ISHAM Working Group on Nomenclature of
`Medical Fungi are Teun Boekhout (CBS-KNAW Fungal Biodiversity
`Centre, Utrecht, The Netherlands, and Institute for Biodiversity and Eco-
`system Dynamics, University of Amsterdam, Amsterdam, The Nether-
`lands), Arunaloke Chakrabarti (Mycology Division, Department of Med-
`ical Microbiology, Postgraduate Institute of Medical Education and
`Research [PGIMER], Chandigarh, India), Anuradha Chowdhary (Vallab-
`hbhai Patel Chest Institute, Delhi, India), Garry Cole (Department of
`Biology and South Texas Center for Emerging Infectious Diseases, Uni-
`versity of Texas at San Antonio, San Antonio, TX), Olivier A. Cornely
`(Department I of Internal Medicine, University Hospital, ZKS Köln,
`BMBF 01KN1106, Cologne and Excellence Cluster on Cellular Stress Re-
`sponses in Aging-Associated Diseases [CECAD], University of Cologne,
`Cologne, Germany), Pedro W. Crous (CBS-KNAW Fungal Biodiversity
`Centre, Utrecht, The Netherlands, and Institute for Biodiversity and Eco-
`system Dynamics, University of Amsterdam, Amsterdam, The Nether-
`lands), Christophe D’Enfert (Fungal Biology and Pathogenicity Unit, In-
`stitut Pasteur, Paris, France), Dea Garcia-Hermoso (Institut Pasteur,
`Unité de Mycologie Moléculaire, Centre National de Référence Mycoses
`Invasives et Antifongiques, Paris, France), D. David Ellis (School of Mo-
`lecular & Biomedical Science, The University of Adelaide, Adelaide, Aus-
`tralia, and National Institute of Allergy and Infectious Diseases, NIH,
`Bethesda, MD), Cornelia Lass-Flörl (Division of Hygiene and Medical
`
`1060 jcm.asm.org
`
`Journal of Clinical Microbiology
`
`April 2015 Volume 53 Number 4
`
`LCY Biotechnology Holding, Inc.
`Ex. 1027
`Page 5 of 7
`
`

`

`Commentary
`
`Microbiology, Innsbruck Medical University, Innsbruck, Austria), Stuart
`Levitz (Center of AIDS Research, University of Massachusetts Medical
`School, Worcester, MA), Ruo-Yu Li (Research Center for Medical Mycol-
`ogy, Peking University, Beijing, China), Aaron P. Mitchell (200B Mellon
`Institute, Department of Biological Sciences, Carnegie Mellon University,
`Pittsburgh, PA), Kerry O’Donnell (Bacterial Foodborne Pathogens & My-
`cology Research Unit, U.S. Department of Agriculture, Agriculture Re-
`search Service, Peoria, IL), John R. Perfect (Department of Medicine,
`Division of Infectious Diseases, Duke University Mycology Research Unit
`[DUMRU], Durham, NC), Flavio Queiroz Telles (Division of Infectious
`Diseases, Department of Public Health, Hospital de Clinicas, Universi-
`dade Federal do Parana, Curitiba, Brazil), Deanna A. Sutton (Fungus
`Testing Laboratory, Department of Pathology, School of Medicine, Uni-
`versity of Texas Health Science Center at San Antonio, San Antonio, TX),
`Kerstin Voigt (Microbial Resource Collection Friedrich-Schiller-Univer-
`sität, Jena, Germany), Theodore C. White (School of Biological Sciences,
`University of Missouri at Kansas City, Kansas City, MO), and Liyan Xi
`(Department of Dermatology, Second Affiliated Hospital, Sun Yat-Sen
`University, Guangzhou, China).
`
`REFERENCES
`
`1. Hawksworth DL, Crous PW, Redhead SA, Reynolds DR, Samson RA,
`Seifert KA, Taylor JW, Wingfield MJ, Abaci O, Aime C, Asan A, Bai FY, de
`Beer ZW, Begerow D, Berikten D, Boekhout T, Buchanan PK, Burgess T,
`Buzina W, Cai L, Cannon PF, Crane JL, Damm U, Daniel HM, van
`Diepeningen AD, Druzhinina I, Dyer PS, Eberhardt U, Fell JW, Frisvad JC,
`Geiser DM, Geml J, Glienke C, Gräfenhan T, Groenewald JZ, Groenewald
`M, de Gruyter J, Guého-Kellermann E, Guo LD, Hibbett DS, Hong SB, de
`Hoog GS, Houbraken J, Huhndorf SM, Hyde KD, Ismail A, Johnston PR,
`Kadaifciler DG, Kirk PM, Kõljalg U, Kurtzman CP, et al. 2011. The
`Amsterdam Declaration on Fungal Nomenclature. IMA Fungus 2:105–112.
`http://dx.doi.org/10.5598/imafungus.2011.02.01.14.
`2. de Hoog GS, Guarro J, Gené J, Figueras MJ (ed). 1995. Atlas of clinical
`fungi, 1st ed. Centraalbureau voor Schimmelcultures, Utrecht, The Neth-
`erlands.
`3. de Hoog GS, Guarro J, Gené J, Figueras MJ (ed). 2013. Atlas of clinical
`fungi, 3A ed. CBS-KNAW Fungal Biodiversity Centre, Utrecht,