DOCSLIB.ORG

Rezafungin—Mechanisms of Action, Susceptibility and Resistance: Similarities and Differences with the Other Echinocandins

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Rezafungin—Mechanisms of Action, Susceptibility and Resistance: Similarities and Differences with the Other Echinocandins Journal of Fungi Review Rezafungin—Mechanisms of Action, Susceptibility and Resistance: Similarities and Differences with the Other Echinocandins Guillermo Garcia-Effron 1,2 1 Laboratorio de Micología y Diagnóstico Molecular, Cátedra de Parasitología y Micología, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, C.P. 3000 Santa Fe, Argentina; [email protected] or guillermo_garciaeff[email protected]; Tel.: +54-9342-4575209 (ext. 135) 2 Consejo Nacional de Investigaciones Científicas y Tecnológicas, C.P. 3000 Santa Fe, Argentina Received: 30 September 2020; Accepted: 22 October 2020; Published: 1 November 2020 Abstract: Rezafungin (formerly CD101) is a new β-glucan synthase inhibitor that is chemically related with anidulafungin. It is considered the first molecule of the new generation of long-acting echinocandins. It has several advantages over the already approved by the Food and Drug Administration (FDA) echinocandins as it has better tissue penetration, better pharmacokinetic/phamacodynamic (PK/PD) pharmacometrics, and a good safety profile. It is much more stable in solution than the older echinocandins, making it more flexible in terms of dosing, storage, and manufacturing. These properties would allow rezafungin to be administered once-weekly (intravenous) and to be potentially administered topically and subcutaneously. In addition, higher dose regimens were tested with no evidence of toxic effect. This will eventually prevent (or reduce) the selection of resistant strains. Rezafungin also has several similarities with older echinocandins as they share the same in vitro behavior (very similar Minimum Inhibitory Concentration required to inhibit the growth of 50% of the isolates (MIC50) and half enzyme maximal inhibitory concentration 50% (IC50)) and spectrum, the same target, and the same mechanisms of resistance. The selection of FKS mutants occurred at similar frequency for rezafungin than for anidulafungin and caspofungin. In this review, rezafungin mechanism of action, target, mechanism of resistance, and in vitro data are described in a comparative manner with the already approved echinocandins. Keywords: rezafungin; CD101; antifungal susceptibility; mechanism of action; mechanism of resistance; literature review 1. Introduction Over 1 billion individuals are affected by fungal infections worldwide. It is estimated that 11.5 million suffer serious infections and that more than 1.5 million people die from fungal diseases each year [1,2]. Since the beginning of this century, there have been great advances in medical mycology including an increased number of diagnostic tools, the development of reliable methods for assessing antifungal susceptibility, the increased knowledge in mechanisms of antifungal resistance and fungal virulence factors, and the development of new drugs [1,2]. One of the greatest improvements in this last area was the incorporation of echinocandins into the antifungal armamentarium. Until the appearance of this class of drugs, the therapeutic options for invasive mycoses were limited to polyenes, 5-fluorocytocin, and azoles, which have only two molecular targets, the fungal membrane and the synthesis of nucleic acids [3,4]. J. Fungi 2020, 6, 262; doi:10.3390/jof6040262 www.mdpi.com/journal/jof J. Fungi 2020, 6, x FOR PEER REVIEW 2 of 23 J. Fungi 2020, 6, 262 2 of 23 2. β-Glucan Synthase Inhibitors Family Tree There are different chemical classes of fungal glucan synthesis inhibitors including lipopeptides 2. β-Glucan Synthase Inhibitors Family Tree (pneumocandins and echinocandins), glycolipids (papulocandins) [5], and triterpenoids (ibrexafungerp)There are [6]. di ffSeveralerent chemicalcompounds classes were eval ofuated fungal to glucanestablish synthesis their antifungal inhibitors potency including and toxicitylipopeptides and even (pneumocandins some molecules and echinocandins),were subjected glycolipidsto clinical (papulocandins)trials. Some of the [5], most and triterpenoids promising molecules(ibrexafungerp) were arbocandins, [6]. Several papulacandins, compounds were enfumagungin, evaluated to establisharundifungin, their antifungaland cilofungin. potency [7–11]. and Onlytoxicity three and echinocandins even some moleculesare currently were in subjectedclinical use to while clinical the trials. safety Some and efficacy of the most of rezafungin promising (echinocandin)molecules were and arbocandins, ibrexafungerp papulacandins, (triterpenoid) enfumagungin, are being evaluated arundifungin, in different and clinical cilofungin trials [12]. [7–11 ]. OnlyThe three three echinocandins FDA-approved are echinocandin currently in drugs clinical are use semisynthetic while the safety derivatives and e ffiofcacy natural of rezafunginproducts. In(echinocandin) 1974, the first andechinocandin-l ibrexafungerpike compound (triterpenoid) was are isolated being evaluatedfrom Aspergillus in different nidulans clinical var. trialsechinulatus [12]. [5,6]. TheIt was three named FDA-approved echinocandin echinocandin B and it drugsbecame are the semisynthetic precedent compound derivatives offor natural anidulafungin products. (LY303366)In 1974, the [5–7]. first echinocandin-like Fifteen year later, compound pneumocandin was isolated was isolated from Aspergillus from Lophium nidulans arboricolavar. echinulatus (homotypic[5,6 ]. synonym:It was named Zalerion echinocandin arboricola B) andand itit became became the the precedent compound compound leading for to anidulafungincaspofungin (MK991) (LY303366) [8].[5 –In7 ]. 1990,Fifteen three year small later, molecules pneumocandin with antifu wasngal isolated properties from Lophiumwere isolated arboricola from(homotypic Coleophoma synonym: empetri (homotypicZalerion arboricola synonym:) and Thabdostrimina it became the empetri compound). Of those, leading WF11899A to caspofungin side chain (MK991) was [8chemically]. In 1990, modifiedthree small to obtain molecules micafungin with antifungal [13]. Rezafungin properties (CD were101, formerly isolated fromSP3025,Coleophoma Cidara Therapeutics) empetri (homotypic is the newestsynonym: memberThabdostrimina of the echinocandin empetri). Of family those, and WF11899A it is the first side member chain was of the chemically second generation modified to of obtain this classmicafungin of antifungals. [13]. Rezafungin (CD101, formerly SP3025, Cidara Therapeutics) is the newest member of the echinocandin family and it is the first member of the second generation of this class of antifungals. 3. Chemistry Characteristics and Differences between Rezafungin and the First Generation Echinocandins:3. Chemistry Characteristics Stability, Stability, and Di andfferences Stability between Rezafungin and the First Generation Echinocandins: Stability, Stability, and Stability Lipopeptide antifungals are cyclic depsipeptides (oligopeptides that have at least one of its amideLipopeptide groups, -C(O)NHR-, antifungals arereplaced cyclic depsipeptidesby its ester, (oligopeptides-C(O)OR) with that different have at least side one chains of its amide[14]. Echinocandinsgroups, -C(O)NHR-, are lipopeptides replaced by with its ester,a cyclic -C(O)OR) hexapeptide with dicorefferent that sidecontains chains uncommon [14]. Echinocandins amino acids are inlipopeptides their structure with such a cyclic as hexapeptide 4-hydroxyproline, core that 3- containshydroxy-4-methilproline, uncommon amino acidsdihydroxyornithine, in their structure and such dihydroxyhomotyrosineas 4-hydroxyproline, 3-hydroxy-4-methilproline, [15]. The depsipeptide core dihydroxyornithine, is N-linked to different and dihydroxyhomotyrosine side chains in each of the [15 ]. drugs.The depsipeptide Caspofungin, core micafungin, is N-linked toand diff anidulafunginerent side chains have in each a fatty-acyl, of the drugs. an Caspofungin,isoxazole 3,5-diphenyl- micafungin, subtituted,and anidulafungin and alkoxytriphenyl have a fatty-acyl, side chains, an isoxazole respecti 3,5-diphenyl-subtituted,vely [10,15] (Figure 1). andWhen alkoxytriphenyl these side chains side arechains, removed respectively by deacetylation, [10,15] (Figure the1 ).cyclic When core these sh sideowed chains no areantifungal removed activity, by deacetylation, demonstrating the cyclic its essentialitycore showed for no echinocandin antifungal activity, activity demonstrating[6]. its essentiality for echinocandin activity [6]. Figure 1. Chemical structure of FDA-approved echinocandins (anidulafungin, caspofungin, Figure 1. Chemical structure of FDA-approved echinocandins (anidulafungin, caspofungin, and micafungin) and rezafungin. In black, the common chemical structure of the four molecules. In red J. Fungi 2020, 6, 262 3 of 23 and micafungin) and rezafungin. In black, the common chemical structure of the four molecules. In red and green, the caspofungin/micafungin and anidulafungin/rezafungin common structures, respectively. In blue, exclusive micafungin chemical structures. In light blue, the choline aminal ether of rezafungin that improves it stability (degradation less likely). Degradation of anidulafungin and rezafungin, modified from [16]. First-generation echinocandins share several pharmacological problems. They have poor oral absorption and average half-lives of 14 h (mouse model) [10], making daily intravenous administration mandatory [17–19]. These drugs also share chemical instability problems such as thermal and hydrolytic degradation for all three echinocandins [17–19] plus photodegradation for micafungin [16,17]. These last inconveniences imply manufacturing and storage
Load more

Recommended publications
  • Evolution and Application of Inteins in Candida Species: a Review
    fmicb-07-01585 October 6, 2016 Time: 13:7 # 1 View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Frontiers - Publisher Connector REVIEW published: 10 October 2016 doi: 10.3389/fmicb.2016.01585 Evolution and Application of Inteins in Candida species: A Review José A. L. Fernandes1†, Tâmara H. R. Prandini2†, Maria da Conceição A. Castro1, Thales D. Arantes1,3, Juliana Giacobino2, Eduardo Bagagli2 and Raquel C. Theodoro1* 1 Institute of Tropical Medicine of Rio Grande do Norte, Universidade Federal do Rio Grande do Norte, Natal, Brazil, 2 Department of Microbiology and Immunology, Institute of Biosciences, Universidade Estadual Paulista Julio de Mesquita Filho, Botucatu, Brazil, 3 Post-graduation Program in Biochemistry, Universidade Federal do Rio Grande do Norte, Natal, Brazil Inteins are invasive intervening sequences that perform an autocatalytic splicing from their host proteins. Among eukaryotes, these elements are present in many fungal species, including those considered opportunistic or primary pathogens, such as Candida spp. Here we reviewed and updated the list of Candida species containing inteins in the genes VMA, THRRS and GLT1 and pointed out the importance of these elements as molecular markers for molecular epidemiological researches and species- specific diagnosis, since the presence, as well as the size of these inteins, is polymorphic Edited by: among the different species. Although absent in Candida albicans, these elements are Joshua D. Nosanchuk, present in different sizes, in some environmental Candida spp. and also in most of the Albert Einstein College of Medicine, USA non-albicans Candida spp. considered emergent opportunistic pathogens.
    [Show full text]
  • Genome Diversity and Evolution in the Budding Yeasts (Saccharomycotina)
    | YEASTBOOK GENOME ORGANIZATION AND INTEGRITY Genome Diversity and Evolution in the Budding Yeasts (Saccharomycotina) Bernard A. Dujon*,†,1 and Edward J. Louis‡,§ *Department Genomes and Genetics, Institut Pasteur, Centre National de la Recherche Scientifique UMR3525, 75724-CEDEX15 Paris, France, †University Pierre and Marie Curie UFR927, 75005 Paris, France, ‡Centre for Genetic Architecture of Complex Traits, and xDepartment of Genetics, University of Leicester, LE1 7RH, United Kingdom ORCID ID: 0000-0003-1157-3608 (E.J.L.) ABSTRACT Considerable progress in our understanding of yeast genomes and their evolution has been made over the last decade with the sequencing, analysis, and comparisons of numerous species, strains, or isolates of diverse origins. The role played by yeasts in natural environments as well as in artificial manufactures, combined with the importance of some species as model experimental systems sustained this effort. At the same time, their enormous evolutionary diversity (there are yeast species in every subphylum of Dikarya) sparked curiosity but necessitated further efforts to obtain appropriate reference genomes. Today, yeast genomes have been very informative about basic mechanisms of evolution, speciation, hybridization, domestication, as well as about the molecular machineries underlying them. They are also irreplaceable to investigate in detail the complex relationship between genotypes and phenotypes with both theoretical and practical implications. This review examines these questions at two distinct levels offered by the broad evolutionary range of yeasts: inside the best-studied Saccharomyces species complex, and across the entire and diversified subphylum of Saccharomycotina. While obviously revealing evolutionary histories at different scales, data converge to a remarkably coherent picture in which one can estimate the relative importance of intrinsic genome dynamics, including gene birth and loss, vs.
    [Show full text]
  • 10-ELS-OXF Kurtzman1610423 CH002 7..20
    Part II Importance of Yeasts Kurtzman 978-0-444-52149-1 00002 Kurtzman 978-0-444-52149-1 00002 Chapter 2 c0002 Yeasts Pathogenic to Humans Chester R. Cooper, Jr. regularly encounter the organisms described below. In fact, many s0010 1. INTRODUCTION TO THE MEDICALLY medical mycologists spend entire careers without direct clinical expo- IMPORTANT YEASTS sure to many of these fungi. Rather, the purpose of this review is to enlighten the non-medical mycologist as to the diversity of yeast and p0010 Prior to global emergence of the human immunodeficiency virus mold species regularly associated with human and animal disease (HIV), which is the causative agent of acquired immunodeficiency that also, at least in part, present a unicellular mode of growth in vivo. syndrome (AIDS), approximately 200 fungal pathogens were recog- The following descriptions present a concise overview of the key p0025 nized from among the more than 100,000 then-known fungal spe- biological and clinical features of these fungi. Where appropriate, refer- cies (Kwon-Chung and Bennett 1992, Rippon 1988). About 50 of ences to recent reviews of particular disease agents and their patholo- these species were regularly associated with fungal disease (myco- gies are provided. For a global perspective of fungal diseases, including sis). Since then, there has been a concurrent dramatic increase in in-depth clinical discussions of specific pathologies, diagnoses, and both the number of known fungal species and the incidence of treatments, the reader is referred to several outstanding and recently mycoses that they cause. Moreover, the spectrum of pathogenic fungi published texts (Anaissie et al.
    [Show full text]
  • Advances in Chemical and Biological Methods to Identify Microorganisms—From Past to Present
    microorganisms Review Advances in Chemical and Biological Methods to Identify Microorganisms—From Past to Present 1,2, 3, 4 4 Ricardo Franco-Duarte y, Lucia Cernˇ áková y , Snehal Kadam , Karishma S. Kaushik , Bahare Salehi 5,* , Antonio Bevilacqua 6, Maria Rosaria Corbo 6, Hubert Antolak 7 , Katarzyna Dybka-St˛epie´n 7 , Martyna Leszczewicz 8 , Saulo Relison Tintino 9, Veruska Cintia Alexandrino de Souza 10, Javad Sharifi-Rad 11,* , Henrique Douglas Melo Coutinho 9,* , Natália Martins 12,13 and Célia F. Rodrigues 14,* 1 CBMA (Centre of Molecular and Environmental Biology), Department of Biology, University of Minho, 4710-057 Braga, Portugal; [email protected] 2 Institute of Science and Innovation for Bio-Sustainability (IB-S), University of Minho, 4710-057 Braga, Portugal 3 Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkoviˇcova6, 842 15 Bratislava, Slovakia; [email protected] 4 Ramalingaswami Re-entry Fellowship, Department of Biotechnology, Government of India, Pune 411045, India; [email protected] (S.K.); [email protected] (K.S.K.) 5 Student Research Committee, School of Medicine, Bam University of Medical Sciences, Bam 14665-354, Iran 6 Department of the Science of Agriculture, Food and Environment, University of Foggia, 71121 Foggia, Italy; [email protected] (A.B.); [email protected] (M.R.C.) 7 Institute of Fermentation Technology and Microbiology, Department of Biotechnology and Food Science, Lodz University of Technology,
    [Show full text]
  • Searching for Telomerase Rnas in Saccharomycetes
    bioRxiv preprint doi: https://doi.org/10.1101/323675; this version posted May 16, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Article TERribly Difficult: Searching for Telomerase RNAs in Saccharomycetes Maria Waldl 1,†, Bernhard C. Thiel 1,†, Roman Ochsenreiter 1, Alexander Holzenleiter 2,3, João Victor de Araujo Oliveira 4, Maria Emília M. T. Walter 4, Michael T. Wolfinger 1,5* ID , Peter F. Stadler 6,7,1,8* ID 1 Institute for Theoretical Chemistry, University of Vienna, Währingerstraße 17, A-1090 Wien, Austria; {maria,thiel,romanoch}@tbi.univie.ac.at, michael.wolfi[email protected] 2 BioInformatics Group, Fakultät CB Hochschule Mittweida, Technikumplatz 17, D-09648 Mittweida, Germany; [email protected] 3 Bioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, University of Leipzig, Härtelstraße 16-18, D-04107 Leipzig, Germany 4 Departamento de Ciência da Computação, Instituto de Ciências Exatas, Universidade de Brasília; [email protected], [email protected] 5 Center for Anatomy and Cell Biology, Medical University of Vienna, Währingerstraße 13, 1090 Vienna, Austria 6 German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, Competence Center for Scalable Data Services and Solutions, and Leipzig Research Center for Civilization Diseases, University Leipzig, Germany 7 Max Planck Institute for Mathematics in the Sciences, Inselstraße 22, D-04103 Leipzig, Germany 8 Santa Fe Institute, 1399 Hyde Park Rd., Santa Fe, NM 87501 * Correspondence: MTW michael.wolfi[email protected]; PFS [email protected] † These authors contributed equally to this work.
    [Show full text]
  • DNA Barcoding Analysis of More Than 1000 Marine Yeast Isolates Reveals Previously Unrecorded Species
    bioRxiv preprint doi: https://doi.org/10.1101/2020.08.29.273490; this version posted September 6, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. DNA barcoding analysis of more than 1000 marine yeast isolates reveals previously unrecorded species Chinnamani PrasannaKumar*1,2, Shanmugam Velmurugan2,3, Kumaran Subramanian4, S. R. Pugazhvendan5, D. Senthil Nagaraj3, K. Feroz Khan2,6, Balamurugan Sadiappan1,2, Seerangan Manokaran7, Kaveripakam Raman Hemalatha8, Bhagavathi Sundaram Sivamaruthi9, Chaiyavat Chaiyasut9 1Biological Oceanography Division, CSIR-National Institute of Oceanography, Dona Paula, Panaji, Goa-403004, India 2Centre of Advance studies in Marine Biology, Annamalai University, Parangipettai, Tamil Nadu- 608502, India 3Madawalabu University, Bale, Robe, Ethiopia 4Centre for Drug Discovery and Development, Sathyabama Institute of Science and Technology, Tamil Nadu-600119, India 5Department of Zoology, Arignar Anna Government Arts College, Cheyyar, Tamil Nadu- 604407, India 6Research Department of Microbiology, Sadakathullah Appa College, Rahmath Nagar, Tirunelveli Tamil Nadu -627 011 7Center for Environment & Water, King Fahd University of Petroleum and Minerals, Dhahran-31261, Saudi Arabia 8Department of Microbiology, Annamalai university, Annamalai Nagar, Chidambaram, Tamil Nadu- 608 002, India 9Innovation Center for Holistic Health, Nutraceuticals, and Cosmeceuticals, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand. *Corresponding author email: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.08.29.273490; this version posted September 6, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
    [Show full text]
  • DNA Barcoding Analysis of More Than 1000 Marine Yeast Isolates Reveals Previously Unrecorded Species
    bioRxiv preprint doi: https://doi.org/10.1101/2020.08.29.273490; this version posted August 29, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. DNA barcoding analysis of more than 1000 marine yeast isolates reveals previously unrecorded species Chinnamani PrasannaKumar*1,2, Shanmugam Velmurugan2,3, Kumaran Subramanian4, S. R. Pugazhvendan5, D. Senthil Nagaraj3, K. Feroz Khan2,6, Balamurugan Sadiappan1,2, Seerangan Manokaran7, Kaveripakam Raman Hemalatha8 1Biological Oceanography Division, CSIR-National Institute of Oceanography, Dona Paula, Panaji, Goa-403004, India 2Centre of Advance studies in Marine Biology, Annamalai University, Parangipettai, Tamil Nadu- 608502, India 3Madawalabu University, Bale, Robe, Ethiopia 4Centre for Drug Discovery and Development, Sathyabama Institute of Science and Technology, Tamil Nadu-600119, India. 5Department of Zoology, Arignar Anna Government Arts College, Cheyyar, Tamil Nadu- 604407, India 6Research Department of Microbiology, Sadakathullah Appa College, Rahmath Nagar, Tirunelveli Tamil Nadu -627 011 7Center for Environment & Water, King Fahd University of Petroleum and Minerals, Dhahran-31261, Saudi Arabia 8Department of Microbiology, Annamalai university, Annamalai Nagar, Chidambaram, Tamil Nadu- 608 002, India Corresponding author email: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.08.29.273490; this version posted August 29, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license.
    [Show full text]
  • The Mechanisms of Mating in Pathogenic Fungi—A Plastic Trait
    G C A T T A C G G C A T genes Review The Mechanisms of Mating in Pathogenic Fungi—A Plastic Trait Jane Usher Medical Research Council Centre for Medical Mycology, Department of Biosciences, University of Exeter, Geoffrey Pope Building, Exeter EX4 4QD, UK; [email protected] Received: 30 August 2019; Accepted: 17 October 2019; Published: 21 October 2019 Abstract: The impact of fungi on human and plant health is an ever-increasing issue. Recent studies have estimated that human fungal infections result in an excess of one million deaths per year and plant fungal infections resulting in the loss of crop yields worth approximately 200 million per annum. Sexual reproduction in these economically important fungi has evolved in response to the environmental stresses encountered by the pathogens as a method to target DNA damage. Meiosis is integral to this process, through increasing diversity through recombination. Mating and meiosis have been extensively studied in the model yeast Saccharomyces cerevisiae, highlighting that these mechanisms have diverged even between apparently closely related species. To further examine this, this review will inspect these mechanisms in emerging important fungal pathogens, such as Candida, Aspergillus, and Cryptococcus. It shows that both sexual and asexual reproduction in these fungi demonstrate a high degree of plasticity. Keywords: mating; meiosis; genomes; MAT (mating type) locus; Candida; Aspergillus; Cryptococcus 1. Introduction There are approximately 1.5 million identified fungal species, of which a few hundred have been reported or suspected of being the causative agent of disease in humans [1]. Human fungal pathogens can cause a myriad of disease, life-threatening infections, chronic infections, and recurrent superficial infections [2].
    [Show full text]
  • Research Article Reconstructing the Backbone of the Saccharomycotina
    G3: Genes|Genomes|Genetics Early Online, published on September 27, 2016 as doi:10.1534/g3.116.034744 Submission: Research Article Reconstructing the backbone of the Saccharomycotina yeast phylogeny using genome- scale data Xing-Xing Shen1, Xiaofan Zhou1, Jacek Kominek2, Cletus P. Kurtzman3,*, Chris Todd Hittinger2,*, and Antonis Rokas1,* 1Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA 2Laboratory of Genetics, Genome Center of Wisconsin, DOE Great Lakes Bioenergy Research Center, Wisconsin Energy Institute, J. F. Crow Institute for the Study of Evolution, University of Wisconsin-Madison, Madison, WI 53706, USA 3Mycotoxin Prevention and Applied Microbiology Research Unit, National Center for Agricultural Utilization Research, Agricultural Research Service, U.S. Department of Agriculture, Peoria, IL 61604, USA *Correspondence: [email protected] or [email protected] or [email protected] Keywords: phylogenomics, maximum likelihood, incongruence, genome completeness, nuclear markers © The Author(s) 2013. Published by the Genetics Society of America. Abstract Understanding the phylogenetic relationships among the yeasts of the subphylum Saccharomycotina is a prerequisite for understanding the evolution of their metabolisms and ecological lifestyles. In the last two decades, the use of rDNA and multi-locus data sets has greatly advanced our understanding of the yeast phylogeny, but many deep relationships remain unsupported. In contrast, phylogenomic analyses have involved relatively few taxa and lineages that were often selected with limited considerations for covering the breadth of yeast biodiversity. Here we used genome sequence data from 86 publicly available yeast genomes representing 9 of the 11 known major lineages and 10 non-yeast fungal outgroups to generate a 1,233-gene, 96-taxon data matrix.
    [Show full text]
  • Computational Discovery of Metabolic Gene Clusters in Yeast
    Computational Discovery of Metabolic Gene Clusters in Yeast Christopher Pyatt A thesis presented for the degree of Doctor of Philosophy University of East Anglia Quadram Institute This copy of the thesis has been supplied on condition that anyone who consults it is understood to recognise that its copyright rests with the author and that use of any information derived therefrom must be in accordance with current UK Copyright Law. In addition, any quotation or extract must include full attribution. September 2019 Abstract Metabolic gene clusters are the genetic source of many natural products (NPs) that can be of use in a range of industries, from medicine and pharmaceuticals to food pro- duction, cosmetics, energy, and environmental remediation. These NPs are synthesised as secondary metabolites by organisms across the tree of life, generally to confer an ephemeral competitive advantage. Finding such gene clusters computationally, from ge- nomic sequence data, promises discovery of novel compounds without expensive and time consuming wet-lab screens. It also allows detection of `cryptic' biosynthetic pathways that would not be found by such screens. The genome sequences of approximately 1,000 yeast strains from the National Collection of Yeast Cultures (NCYC) were searched for both known and unknown metabolic gene clusters, to assess the NP potential of the collection and investigate the evolution of gene clusters in yeast. Variants of gene clusters encoding popular biosurfactants were found in tight-knit taxonomic groups. The mannosylerythritol lipid (MEL) gene cluster was found to be composed of unique genes and constrained to a small number of species, suggesting a period of substantial evolutionary change in its history.
    [Show full text]
  • Prevalence of Human Pathogens of the Clade Nakaseomyces in a Culture Collection—The First Report on Candida Bracarensis in Poland
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Jagiellonian Univeristy Repository Folia Microbiologica (2019) 64:307–312 https://doi.org/10.1007/s12223-018-0655-7 ORIGINAL ARTICLE Prevalence of human pathogens of the clade Nakaseomyces in a culture collection—the first report on Candida bracarensis in Poland Marianna Małek1 & Paulina Mrowiec1 & Karolina Klesiewicz1 & Iwona Skiba-Kurek1 & Adrian Szczepański2 & Joanna Białecka3 & Iwona Żak4 & Bożena Bogusz5 & Jolanta Kędzierska2 & Alicja Budak1 & Elżbieta Karczewska1 Received: 13 May 2018 /Accepted: 8 October 2018 /Published online: 25 October 2018 # The Author(s) 2018 Abstract Human pathogens belonging to the Nakaseomyces clade include Candida glabrata sensu stricto, Candida nivariensis and Candida bracarensis. Their highly similar phenotypic characteristics often lead to misidentification by conventional laboratory methods. Therefore, limited information on the true epidemiology of the Candida glabrata species complex is available. Due to life-threatening infections caused by these species, it is crucial to supplement this knowledge. The aim of the study was to estimate the prevalence of C. bracarensis and C. nivariensis in a culture collection of C. glabrata complex isolates. The study covered 353 isolates identified by biochemical methods as C. glabrata, collected from paediatric and adult patients hospitalised at four medical centres in Southern Poland. The multiplex PCR was used to identify the strains. Further species confirmation was performed via sequencing and matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) analysis. One isolate was recognised as C. bracarensis (0.28%). To our knowledge, it is the first isolate in Poland.
    [Show full text]
  • Descriptions of Medical Fungi
    DESCRIPTIONS OF MEDICAL FUNGI THIRD EDITION (revised November 2016) SARAH KIDD1,3, CATRIONA HALLIDAY2, HELEN ALEXIOU1 and DAVID ELLIS1,3 1NaTIONal MycOlOgy REfERENcE cENTRE Sa PaTHOlOgy, aDElaIDE, SOUTH aUSTRalIa 2clINIcal MycOlOgy REfERENcE labORatory cENTRE fOR INfEcTIOUS DISEaSES aND MIcRObIOlOgy labORatory SERvIcES, PaTHOlOgy WEST, IcPMR, WESTMEaD HOSPITal, WESTMEaD, NEW SOUTH WalES 3 DEPaRTMENT Of MOlEcUlaR & cEllUlaR bIOlOgy ScHOOl Of bIOlOgIcal ScIENcES UNIvERSITy Of aDElaIDE, aDElaIDE aUSTRalIa 2016 We thank Pfizera ustralia for an unrestricted educational grant to the australian and New Zealand Mycology Interest group to cover the cost of the printing. Published by the authors contact: Dr. Sarah E. Kidd Head, National Mycology Reference centre Microbiology & Infectious Diseases Sa Pathology frome Rd, adelaide, Sa 5000 Email: [email protected] Phone: (08) 8222 3571 fax: (08) 8222 3543 www.mycology.adelaide.edu.au © copyright 2016 The National Library of Australia Cataloguing-in-Publication entry: creator: Kidd, Sarah, author. Title: Descriptions of medical fungi / Sarah Kidd, catriona Halliday, Helen alexiou, David Ellis. Edition: Third edition. ISbN: 9780646951294 (paperback). Notes: Includes bibliographical references and index. Subjects: fungi--Indexes. Mycology--Indexes. Other creators/contributors: Halliday, catriona l., author. Alexiou, Helen, author. Ellis, David (David H.), author. Dewey Number: 579.5 Printed in adelaide by Newstyle Printing 41 Manchester Street Mile End, South australia 5031 front cover: Cryptococcus neoformans, and montages including Syncephalastrum, Scedosporium, Aspergillus, Rhizopus, Microsporum, Purpureocillium, Paecilomyces and Trichophyton. back cover: the colours of Trichophyton spp. Descriptions of Medical Fungi iii PREFACE The first edition of this book entitled Descriptions of Medical QaP fungi was published in 1992 by David Ellis, Steve Davis, Helen alexiou, Tania Pfeiffer and Zabeta Manatakis.
    [Show full text]