Genomic Characterization and Virulence Potential of Two Fusarium oxysporum Isolates Cultured from the International Space Station

This is the first study to isolate and characterize F. oxysporum isolates from a built environment, as well as one that has been exposed to space. The characterization and analysis of these two genomes may have important implications for the medical, agricultural, and food industries as well as for the health of the crew who coinhabit the ISS with these strains. ABSTRACT Two isolates of Fusarium oxysporum, ISS-F3 and ISS-F4, were cultured from the dining table on the International Space Station (ISS). Genomic analyses using EF-1α sequences, presence/absence of effector proteins, k-mer comparisons, and single nucleotide polymorphisms indicate that these two strains are genomically different from 65 known sequenced strains. Functional analysis revealed that ISS-F3/F4 had higher relative abundances of polyketide synthase domains than a non-plant-pathogenic soil isolate, used for biocontrol properties (Fo47), and a clinical isolate (FOSC-3a). Putative secondary metabolite analysis indicates that ISS-F3/F4 may produce yet-unreported polyketides and nonribosomal peptides. While genomic analysis showed that these ISS strains are unlikely to be plant pathogens, a virulence assay using an immunocompromised Caenorhabditis elegans model of fusariosis revealed that they were virulent and may represent opportunistic pathogens in animals, including humans. However, its effects on the health of immunocompromised humans warrant further study. IMPORTANCE This is the first study to isolate and characterize F. oxysporum isolates from a built environment, as well as one that has been exposed to space. The characterization and analysis of these two genomes may have important implications for the medical, agricultural, and food industries as well as for the health of the crew who coinhabit the ISS with these strains.

[1]  M. Nucci,et al.  Fusariosis , 2020, Definitions.

[2]  Jason M. Wood,et al.  Succession and persistence of microbial communities and antimicrobial resistance genes associated with International Space Station environmental surfaces , 2018, Microbiome.

[3]  K. Venkateswaran,et al.  Draft Genome Sequences of Two Fusarium oxysporum Isolates Cultured from Infected Zinnia hybrida Plants Grown on the International Space Station , 2018, Genome Announcements.

[4]  V. Katkar,et al.  Urinary tract infection due to Fusarium oxysporum in an immunocompetent patient with chronic kidney disease , 2017, Journal of biomedical research.

[5]  L. Fokkens,et al.  A mobile pathogenicity chromosome in Fusarium oxysporum for infection of multiple cucurbit species , 2017, Scientific Reports.

[6]  T. Gordon.  Fusarium oxysporum and the Fusarium Wilt Syndrome. , 2017, Annual review of phytopathology.

[7]  Y. Pérez-Pertejo,et al.  Antileishmanial activity and tubulin polymerization inhibition of podophyllotoxin derivatives on Leishmania infantum , 2017, International journal for parasitology. Drugs and drug resistance.

[8]  S. Taj-Aldeen.  Reduced Multidrug Susceptibility Profile Is a Common Feature of Opportunistic Fusarium Species: Fusarium Multi-Drug Resistant Pattern , 2017, Journal of fungi.

[9]  P. L. Chang,et al.  Races of the Celery Pathogen Fusarium oxysporum f. sp. apii Are Polyphyletic. , 2017, Phytopathology.

[10]  B. N. Johri,et al.  Fusarium oxysporum: Genomics, Diversity and Plant–Host Interaction , 2017 .

[11]  M. T. A. Abdel-Wareth,et al.  Fungal Metabolites. , 1971, International Journal of Environmental Studies.

[12]  K. J. Brown,et al.  Chapter 20 – Fungal Metabolites , 2017 .

[13]  T. Satyanarayana,et al.  Developments in Fungal Biology and Applied Mycology , 2017, Springer Singapore.

[14]  Simone Badal Mccreath,et al.  Pharmacognosy: Fundamentals, Applications and Strategies , 2016 .

[15]  L. Fokkens,et al.  Effector profiles distinguish formae speciales of Fusarium oxysporum. , 2016, Environmental microbiology.

[16]  Kasthuri Venkateswaran,et al.  Characterization of Aspergillus fumigatus Isolates from Air and Surfaces of the International Space Station , 2016, mSphere.

[17]  S. Sukno,et al.  The FTF gene family regulates virulence and expression of SIX effectors in Fusarium oxysporum , 2016, Molecular plant pathology.

[18]  P. Bork,et al.  ETE 3: Reconstruction, Analysis, and Visualization of Phylogenomic Data , 2016, Molecular biology and evolution.

[19]  Po-E Li,et al.  From raw reads to trees: Whole genome SNP phylogenetics across the tree of life , 2015, bioRxiv.

[20]  A. Stierle,et al.  Bioactive Secondary Metabolites Produced by the Fungal Endophytes of Conifers , 2015, Natural product communications.

[21]  Pedro W. Crous,et al.  DNA sequence-based identification of Fusarium: Current status and future directions , 2015, Phytoparasitica.

[22]  H. Giese,et al.  An update to polyketide synthase and non-ribosomal synthetase genes and nomenclature in Fusarium. , 2015, Fungal genetics and biology : FG & B.

[23]  Sebastian Deorowicz,et al.  KMC 2: Fast and resource-frugal k-mer counting , 2014, Bioinform..

[24]  B. Moore,et al.  Fungal polyketide engineering comes of age , 2014, Proceedings of the National Academy of Sciences.

[25]  Wendy S. Schackwitz,et al.  Evolution of extreme resistance to ionizing radiation via genetic adaptation of DNA repair , 2013, eLife.

[26]  A. Di Pietro,et al.  Murine Model for Fusarium oxysporum Invasive Fusariosis Reveals Organ-Specific Structures for Dissemination and Long-Term Persistence , 2014, PloS one.

[27]  Xiaoqiu Huang,et al.  The Genome Sequence of the Fungal Pathogen Fusarium virguliforme That Causes Sudden Death Syndrome in Soybean , 2014, PloS one.

[28]  E. G. de Macedo Lemos,et al.  Biotechnology of polyketides: New breath of life for the novel antibiotic genetic pathways discovery through metagenomics , 2013, Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology].

[29]  Richard D. Smith,et al.  Phosphate-Containing Polyethylene Glycol Polymers Prevent Lethal Sepsis by Multidrug-Resistant Pathogens , 2013, Antimicrobial Agents and Chemotherapy.

[30]  P. R. Rajamohanan,et al.  Isolation, Purification and Characterization of Vinblastine and Vincristine from Endophytic Fungus Fusarium oxysporum Isolated from Catharanthus roseus , 2013, PloS one.

[31]  E. Mylonakis,et al.  Invertebrate models of fungal infection. , 2013, Biochimica et biophysica acta.

[32]  A. Cruz,et al.  Bioactive extracts and chemical constituents of two endophytic strains of Fusarium oxysporum , 2012 .

[33]  A. Villanueva,et al.  Basic Caenorhabditis elegans methods: synchronization and observation. , 2012, Journal of visualized experiments : JoVE.

[34]  J. Guarro,et al.  A PR-1-like Protein of Fusarium oxysporum Functions in Virulence on Mammalian Hosts* , 2012, The Journal of Biological Chemistry.

[35]  J. Manners,et al.  A highly conserved effector in Fusarium oxysporum is required for full virulence on Arabidopsis. , 2012, Molecular plant-microbe interactions : MPMI.

[36]  K. Romanowski,et al.  Host stress and virulence expression in intestinal pathogens: development of therapeutic strategies using mice and C. elegans. , 2011, Current pharmaceutical design.

[37]  E. Mylonakis,et al.  From the outside in and the inside out: Antifungal immune responses in Caenorhabditis elegans , 2010, Virulence.

[38]  Christina A. Cuomo,et al.  Source (or Part of the following Source): Type Article Title Comparative Genomics Reveals Mobile Pathogenicity Chromosomes in Fusarium Author(s) , 2022 .

[39]  Frederick M. Ausubel,et al.  Evolution of host innate defence: insights from Caenorhabditis elegans and primitive invertebrates , 2010, Nature Reviews Immunology.

[40]  K. Borges,et al.  Endophytic Fungi: Natural Products, Enzymes and Biotransformation Reactions , 2009 .

[41]  Steven J. M. Jones,et al.  Abyss: a Parallel Assembler for Short Read Sequence Data Material Supplemental Open Access , 2022 .

[42]  Thomas J. Simpson,et al.  COMPLEX ENZYMES IN MICROBIAL NATURAL PRODUCT BIOSYNTHESIS, PART B: POLYKETIDES, AMINOCOUMARINS AND CARBOHYDRATES , 2009 .

[43]  David A Hopwood.  Complex enzymes in microbial natural product biosynthesis, part B: polyketides, aminocoumarins and carbohydrates. Preface. , 2009, Methods in enzymology.

[44]  Michael G Thomas,et al.  Biosynthesis of polyketide synthase extender units. , 2009, Natural product reports.

[45]  O. Gascuel,et al.  Estimating maximum likelihood phylogenies with PhyML. , 2009, Methods in molecular biology.

[46]  V. Verma,et al.  Isolation and identification of an endophytic strain of Fusarium oxysporum producing podophyllotoxin from Juniperus recurva , 2008 .

[47]  F. Ausubel,et al.  Models of Caenorhabditis elegans infection by bacterial and fungal pathogens. , 2008, Methods in molecular biology.

[48]  E. Anaissie,et al.  Fusarium Infections in Immunocompromised Patients , 2007, Clinical Microbiology Reviews.

[49]  Arturo Casadevall,et al.  Exploiting Amoeboid and Non-Vertebrate Animal Model Systems to Study the Virulence of Human Pathogenic Fungi , 2007, PLoS pathogens.

[50]  S. Husain,et al.  Fungal infections in solid organ transplantation. , 2007, Medical mycology.

[51]  C. D. de Koster,et al.  The mixed xylem sap proteome of Fusarium oxysporum-infected tomato plants. , 2007, Molecular plant pathology.

[52]  E. Mylonakis.  Galleria mellonella and the Study of Fungal Pathogenesis: Making the Case for Another Genetically Tractable Model Host , 2007, Mycopathologia.

[53]  Valerie Reinke,et al.  p38 MAPK Regulates Expression of Immune Response Genes and Contributes to Longevity in C. elegans , 2006, PLoS genetics.

[54]  A. Gunatilaka.  Natural products from plant-associated microorganisms: distribution, structural diversity, bioactivity, and implications of their occurrence. , 2006, Journal of natural products.

[55]  Juan Miguel García-Gómez,et al.  BIOINFORMATICS APPLICATIONS NOTE Sequence analysis Manipulation of FASTQ data with Galaxy , 2005 .

[56]  Burkhard Morgenstern,et al.  AUGUSTUS: a web server for gene prediction in eukaryotes that allows user-defined constraints , 2005, Nucleic Acids Res..

[57]  J. Robinson,et al.  Genetic Diversity of Human Pathogenic Members of the Fusarium oxysporum Complex Inferred from Multilocus DNA Sequence Data and Amplified Fragment Length Polymorphism Analyses: Evidence for the Recent Dispersion of a Geographically Widespread Clonal Lineage and Nosocomial Origin , 2004, Journal of Clinical Microbiology.

[58]  M. Gordaliza,et al.  Podophyllotoxin: distribution, sources, applications and new cytotoxic derivatives. , 2004, Toxicon : official journal of the International Society on Toxinology.

[59]  C. D. de Koster,et al.  A small, cysteine‐rich protein secreted by Fusarium oxysporum during colonization of xylem vessels is required for I‐3‐mediated resistance in tomato , 2004, Molecular microbiology.

[60]  Robert C. Edgar,et al.  MUSCLE: multiple sequence alignment with high accuracy and high throughput. , 2004, Nucleic acids research.

[61]  J. Guarro,et al.  Fusarium oxysporum as a Multihost Model for the Genetic Dissection of Fungal Virulence in Plants and Mammals , 2004, Infection and Immunity.

[62]  M. C. Dignani,et al.  Human fusariosis. , 2004, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[63]  P. Leadlay,et al.  Biosynthetic engineering of polyketide synthases , 2003 .

[64]  J. Sierra,et al.  Synthesis, cytotoxicity and antiviral activity of podophyllotoxin analogues modified in the E-ring. , 2003, European journal of medicinal chemistry.

[65]  Mario Stanke,et al.  Gene prediction with a hidden Markov model and a new intron submodel , 2003, ECCB.

[66]  C. Alabouvette,et al.  Fusarium oxysporum and its biocontrol. , 2003, The New phytologist.

[67]  S. Rosendahl,et al.  Population structure and pathogenicity of members of the Fusarium oxysporum complex isolated from soil and root necrosis of pea (Pisum sativum L.). , 2002, FEMS microbiology ecology.

[68]  Frederick M. Ausubel,et al.  A Conserved p38 MAP Kinase Pathway in Caenorhabditis elegans Innate Immunity , 2002, Science.

[69]  F. Ausubel,et al.  Caenorhabditis elegans as a host for the study of host-pathogen interactions. , 2002, Current opinion in microbiology.

[70]  J. Lown,,et al.  Podophyllotoxins: current status and recent developments. , 1998, Current medicinal chemistry.

[71]  R. Ploetz,et al.  Multiple evolutionary origins of the fungus causing Panama disease of banana: concordant evidence from nuclear and mitochondrial gene genealogies. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[72]  U. Beyer,et al.  Systemic Fusarium oxysporum infection in an immunocompetent patient with an adult respiratory distress syndrome (ARDS) and extracorporal membrane oxygenation (ECMO) , 1998, Mycoses.

[73]  S. Strome,et al.  Characterization of a germ-line proliferation mutation in C. elegans. , 1992, Development.

[74]  G. Gaedicke,et al.  A fatal infection due to Fusarium oxysporum in a child with Wilms' tumour. Case report and review of the literature , 1992, Mycoses.

[75]  R. Cook,et al.  Fusarium: Diseases, Biology, and Taxonomy , 1982 .

[76]  Gm Armstrong,et al.  FORMAE SPECIALES AND RACES OF FUSARIUM OXYSPORUM CAUSING WILT DISEASES , 1981 .