Siderophore Biosynthesis and Transport Systems in Model and Pathogenic Fungi
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Fungi employ diverse mechanisms for iron uptake to ensure proliferation and survival in ironlimited environments. Siderophores are secondary metabolite small molecules with a high affinity specifically for ferric iron; these molecules play an essential role in iron acquisition in fungi and significantly influence fungal physiology and virulence. Fungal siderophores, which are primarily hydroxamate types, are synthesized via non-ribosomal peptide synthetases (NRPS) or NRPSindependent pathways. Following synthesis, siderophores are excreted, chelate iron, and are transported into the cell by specific cell membrane transporters. In several human pathogenic fungi, siderophores are pivotal for virulence, as inhibition of their synthesis or transport significantly reduces disease in murine models of infection. This review briefly highlights siderophore biosynthesis and transport mechanisms in fungal pathogens as well the model fungi Saccharomyces cerevisiae and Schizosaccharomyces pombe. Understanding siderophore biosynthesis and transport in pathogenic fungi provides valuable insights into fungal biology and illuminates potential therapeutic targets for combating fungal infections.
Abstract
Fungi employ diverse mechanisms for iron uptake to ensure proliferation and survival in ironlimited environments. Siderophores are secondary metabolite small molecules with a high affinity specifically for ferric iron; these molecules play an essential role in iron acquisition in fungi and significantly influence fungal physiology and virulence. Fungal siderophores, which are primarily hydroxamate types, are synthesized via non-ribosomal peptide synthetases (NRPS) or NRPSindependent pathways. Following synthesis, siderophores are excreted, chelate iron, and are transported into the cell by specific cell membrane transporters. In several human pathogenic fungi, siderophores are pivotal for virulence, as inhibition of their synthesis or transport significantly reduces disease in murine models of infection. This review briefly highlights siderophore biosynthesis and transport mechanisms in fungal pathogens as well the model fungi Saccharomyces cerevisiae and Schizosaccharomyces pombe. Understanding siderophore biosynthesis and transport in pathogenic fungi provides valuable insights into fungal biology and illuminates potential therapeutic targets for combating fungal infections.
참고문헌 (123)
- Puja H, "Engineering Siderophore biosynthesis and regulation pathways to increase diversity and availability", Biomolecules, 13, pp.959~ (2023)
- Timofeeva AM, "Bacterial siderophores : classification, biosynthesis, perspectives of use in agriculture", Plants(Basel), 11, pp.3065~ (2022)
- Pecoraro L, "Biosynthesis pathways, transport mechanisms and biotechnological applications of fungal siderophores", J. Fungi(Basel), 8, pp.21~ (2021)
- Neilands JB, "A crystalline organo-iron pigment from a rust fungus(Ustilago-Sphaerogena)", J. Am. Chem. Soc, 74, pp.4846~4847 (1952)
- Hesseltine CW, "Coprogen, a new growth factor for coprophilic fungi", J. Am. Chem. Soc, 74, pp.1362~1362 (1952)
- Hider RC, "Chemistry and biology of siderophores", Nat. Prod. Rep, 27, pp.637~657 (2010)
- Ito T, "Products of low-iron fermentation with Bacillus-Subtilis-isolation, characterization and synthesis of 2, 3-dihydroxybenzoylglycine", J. Am. Chem. Soc, 80, pp.4645~4647 (1958)
- Thieken A, "Rhizoferrin : a complexone type siderophore of the Mucorales and entomophthorales(Zygomycetes)", FEMS Microbiol. Lett, 73, pp.37~41 (1992)
- Holinsworth B, "Siderophore production by marine-derived fungi", Biometals, 22, pp.625~632 (2009)
- Ismail A, "Siderophore production by Salmonella typhi", Biochem. Biophys. Res. Commun, 150, pp.18~24 (1988)
- Khan A, "Synthesis, nature and utility of universal iron chelator - Siderophore: A review", Microbiol. Res, 212-213, pp.103~111 (2018)
- Braud A, "Presence of the siderophores pyoverdine and pyochelin in the extracellular medium reduces toxic metal accumulation in Pseudomonas aeruginosa and increases bacterial metal tolerance", Environ. Microbiol. Rep, 2, pp.419~425 (2010)
- Braun V, "Recent insights into iron import by bacteria", Curr. Opin. Chem. Biol, 15, pp.328~334 (2011)
- Das A, "Microbial Siderophores" (2007), Springer Berlin Heidelberg
- Kragl C, "EstB-mediated hydrolysis of the siderophore triacetylfusarinine C optimizes iron uptake of Aspergillus fumigatus", Eukaryot Cell, 6, pp.1278~1285 (2007)
- Yun CW, "The role of the FRE family of plasma membrane reductases in the uptake of siderophore-iron in Saccharomyces cerevisiae", J. Biol. Chem, 276, pp.10218~10223 (2001)
- Schrettl M, "The crucial role of the Aspergillus fumigatus siderophore system in interaction with alveolar macrophages", Microbes Infect, 12, pp.1035~1041 (2010)
- Aguiar M, "Uptake of the siderophore triacetylfusarinine C, but not fusarinine C, is crucial for virulence of Aspergillus fumigatus", mBio, 13, pp.e0219222~ (2022)
- Hwang LH, "Histoplasma requires SID1, a member of an iron-regulated siderophore gene cluster, for host colonization", PLoS Pathog, 4, pp.e1000044~ (2008)
- Heymann P, "Identification of a fungal triacetylfusarinine C siderophore transport gene(TAF1)in Saccharomyces cerevisiae as a member of the major facilitator superfamily", Biometals, 12, pp.301~306 (1999)
- Heymann P, "A gene of the major facilitator superfamily encodes a transporter for enterobactin(Enb1p)in Saccharomyces cerevisiae", Biometals, 13, pp.65~72 (2000)
- Heymann P, "Identification and substrate specificity of a ferrichrome-type siderophore transporter(Arn1p)in Saccharomyces cerevisiae", FEMS Microbiol. Lett, 186, pp.221~227 (2000)
- Lesuisse E, "Siderophore-mediated iron uptake in Saccharomyces cerevisiae : the SIT1 gene encodes a ferrioxamine B permease that belongs to the major facilitator superfamily", Microbiology(Reading), 144(Pt 12), pp.3455~3462 (1998)
- Pelletier B, "Fep1 represses expression of the fission yeast siderophore-iron transport system", Nucleic Acids Res, 31, pp.4332~4344 (2003)
- Hu CJ, "Characterization and functional analysis of the siderophore-iron transporter CaArn1p in Candida albicans", J. Biol. Chem, 277, pp.30598~30605 (2002)
- Kim Y, "Ferrichrome induces endosome to plasma membrane cycling of the ferrichrome transporter, Arn1p, in Saccharomyces cerevisiae", EMBO J, 21, pp.3632~3642 (2002)
- Moore RE, "The mechanism of ferrichrome transport through Arn1p and its metabolism in Saccharomyces cerevisiae", Proc. Natl. Acad. Sci. USA, 100, pp.5664~5669 (2003)
- Erpapazoglou Z, "Substrate-and ubiquitindependent trafficking of the yeast siderophore transporter Sit1", Traffic, 9, pp.1372~1391 (2008)
- Jeong MY, "A novel function of Aft1 in regulating ferrioxamine B uptake : Aft1 modulates Arn3 ubiquitination in Saccharomyces cerevisiae", Biochem. J, 422, pp.181~191 (2009)
- Rutherford JC, "A second iron-regulatory system in yeast independent of Aft1p", Proc. Natl. Acad. Sci. USA, 98, pp.14322~14327 (2001)
- Martinez-Pastor MT, "Mechanisms of iron sensing and regulation in the yeast Saccharomyces cerevisiae", World J. Microbiol. Biotechnol, 33, pp.75~ (2017)
- Courel M, "Direct activation of genes involved in intracellular iron use by the yeast ironresponsive transcription factor Aft2 without its paralog Aft1", Mol. Cell. Biol, 25, pp.6760~6771 (2005)
- Ramos-Alonso L, "Iron regulatory mechanisms in Saccharomyces cerevisiae", Front. Microbiol, 11, pp.582830~ (2020)
- Li L, "Yap5 is an iron-responsive transcriptional activator that regulates vacuolar iron storage in yeast", Mol. Cell. Biol, 28, pp.1326~1337 (2008)
- Outten CE, "Iron sensing and regulation in Saccharomyces cerevisiae : Ironing out the mechanistic details", Curr. Opin. Microbiol, 16, pp.662~668 (2013)
- Yamaguchi-Iwai Y, "Iron-regulated DNA binding by the AFT1 protein controls the iron regulon in yeast", EMBO J, 15, pp.3377~3384 (1996)
- Rutherford JC, "Aft1p and Aft2p mediate iron-responsive gene expression in yeast through related promoter elements", J. Biol. Chem, 278, pp.27636~27643 (2003)
- Kang CM, "Physical interaction between Sit1 and Aft1 upregulates FOB uptake activity by inhibiting protein degradation of Sit1 in Saccharomyces cerevisiae", FEMS Yeast Res, 15, pp.fov080~ (2015)
- Fragiadakis GS, "Nhp6 facilitates Aft1 binding and Ssn6 recruitment, both essential for FRE2transcriptional activation", EMBO J, 23, pp.333~342 (2004)
- Crisp RJ, "Recruitment of Tup1p and Cti6p regulates heme-deficient expression of Aft1p target genes", EMBO J, 25, pp.512~521 (2006)
- Protchenko O, "Three cell wall mannoproteins facilitate the uptake of iron in Saccharomyces cerevisiae", J. Biol. Chem, 276, pp.49244~49250 (2001)
- Park YS, "Sed1p interacts with Arn3p physically and mediates ferrioxamine B uptake in Saccharomyces cerevisiae", Curr. Genet, 47, pp.150~155 (2005)
- Vyas A, "Fission Yeast Schizosaccharomyces pombe : A Unicellular"Micromammal"model organism", Curr. Protoc, 1, pp.e151~ (2021)
- Schrettl M, "Ferrichrome in Schizosaccharomyces pombe--an iron transport and iron storage compound", Biometals, 17, pp.647~654 (2004)
- Haas H, "Molecular genetics of fungal siderophore biosynthesis and uptake : the role of siderophores in iron uptake and storage", Appl. Microbiol. Biotechnol, 62, pp.316~330 (2003)
- Schwecke T, "Nonribosomal peptide synthesis in Schizosaccharomyces pombe and the architectures of ferrichrome-type siderophore synthetases in fungi", Chembiochem, 7, pp.612~622 (2006)
- Brault A, "Sib1, Sib2, and Sib3 proteins are required for ferrichrome-mediated cross-feeding interaction between Schizosaccharomyces pombe and Saccharomyces cerevisiae", Front. Microbiol, 13, pp.962853~ (2022)
- Pelletier B, "Fep1 represses expression of the fission yeast Schizosaccharomyces pombe siderophore-iron transport system", Nucleic Acids Res, 31, pp.4332~4344 (2003)
- Plante S, "Spore Germination requires ferrichrome biosynthesis and the siderophore transporter Str1 in Schizosaccharomyces pombe", Genetics, 211, pp.893~911 (2019)
- Yu C, "Progress in pathogenesis research of Ustilago maydis, and the metabolites involved along with their biosynthesis", Mol. Plant Pathol, 24, pp.495~509 (2023)
- Budde AD, "Characterization of siderophores from Ustilago maydis", Mycopathologia, 108, pp.125~133 (1989)
- Wang J, "Analysis of ferrichrome biosynthesis in the phytopathogenic fungus Ustilago maydis : cloning of an ornithine-N5-oxygenase gene", J. Bacteriol, 171, pp.2811~2818 (1989)
- Mei B, "sid1, a gene initiating siderophore biosynthesis in Ustilago maydis : molecular characterization, regulation by iron, and role in phytopathogenicity", Proc. Natl. Acad. Sci. USA, 90, pp.903~907 (1993)
- Yuan WM, "Characterization of the Ustilago maydis sid2 gene, encoding a multidomain peptide synthetase in the ferrichrome biosynthetic gene cluster", J. Bacteriol, 183, pp.4040~4051 (2001)
- Winterberg B, "Elucidation of the complete ferrichrome A biosynthetic pathway in Ustilago maydis", Mol. Microbiol, 75, pp.1260~1271 (2010)
- Servouse M, "Regulation of early enzymes of ergosterol biosynthesis in Saccharomyces cerevisiae", Biochem J, 240, pp.541~547 (1986)
- Eichhorn H, "A ferroxidation", permeation iron uptake system is required for virulence in Ustilago maydis, 2006, pp.18, 3332~3345
- Antelo L, "Siderophores produced by Magnaporthe grisea in the presence and absence of iron", Z Naturforsch C J. Biosci, 61, pp.461~464 (2006)
- Hof C, "Ferricrocin synthesis in Magnaporthe grisea and its role in pathogenicity in rice", Mol. Plant Pathol, 8, pp.163~172 (2007)
- Hof C, "Siderophore synthesis in is essential for vegetative growth, conidiation and resistance to oxidative stress", Fungal Genet. Biol, 46, pp.321~332 (2009)
- Kwon-Chung KJ, "Aspergillus fumigatus--what makes the species a ubiquitous human fungal pathogen?", PLoS Pathog, 9, pp.e1003743~ (2013)
- Baddley JW, "Aspergillosis in Intensive Care Unit(ICU)patients : epidemiology and economic outcomes", BMC Infect. Dis, 13, pp.29~ (2013)
- Brown GD, "Hidden killers : human fungal infections", Sci. Transl. Med, 4, pp.165rv113~ (2012)
- Nilius AM, "Identification of extracellular siderophores of pathogenic strains of Aspergillus fumigatus", J. Med. Vet. Mycol, 28, pp.395~403 (1990)
- Haas H, "Fungal siderophore metabolism with a focus on Aspergillus fumigatus", Nat. Prod. Rep, 31, pp.1266~1276 (2014)
- Schrettl M, "Distinct roles for intra-and extracellular siderophores during Aspergillus fumigatus infection", PLoS Pathog, 3, pp.1195~1207 (2007)
- Hissen AH, "The Aspergillus fumigatus siderophore biosynthetic gene sidA, encoding L-ornithine N5-oxygenase, is required for virulence", Infect. Immun, 73, pp.5493~5503 (2005)
- Blatzer M, "SidL, an Aspergillus fumigatus transacetylase involved in biosynthesis of the siderophores ferricrocin and hydroxyferricrocin", Appl. Environ. Microbiol, 77, pp.4959~4966 (2011)
- Yasmin S, "Mevalonate governs interdependency of ergosterol and siderophore biosyntheses in the fungal pathogen Aspergillus fumigatus", Proc. Natl. Acad. Sci. USA, 109, pp.E497~E504 (2012)
- Schrettl M, "HapX-mediated adaption to iron starvation is crucial for virulence of Aspergillus fumigatus", PLoS Pathog, 6, pp.e1001124~ (2010)
- Martinez-Pastor MT, "Adaptation to iron deficiency in human pathogenic fungi", Biochim. Biophys. Acta Mol. Cell Res, 1867, pp.118797~ (2020)
- Haas H, "Siderophores in fungal physiology and virulence", Annu. Rev. Phytopathol, 46, pp.149~187 (2008)
- Mulvihill ED, "Functional Investigation of Iron-Responsive Microsomal Proteins, including MirC, in Aspergillus fumigatus", Front. Microbiol, 8, pp.418~ (2017)
- Park YS, "Identification of ferrichrome-and ferrioxamine B-mediated iron uptake by Aspergillus fumigatus", Biochem. J, 473, pp.1203~1213 (2016)
- Haas H, "Characterization of the Aspergillus nidulans transporters for the siderophores enterobactin and triacetylfusarinine C", Biochem. J, 371, pp.505~513 (2003)
- Oberegger H, "SREA is involved in regulation of siderophore biosynthesis, utilization and uptake in Aspergillus nidulans", Mol. Microbiol, 41, pp.1077~1089 (2001)
- Raymond-Bouchard I, "Structural requirements for the activity of the MirB ferrisiderophore transporter of Aspergillus fumigatus", Eukaryot. Cell, 11, pp.1333~1344 (2012)
- Schrettl M, "SreA-mediated iron regulation in Aspergillus fumigatus", Mol. Microbiol, 70, pp.27~43 (2008)
- Heymann P, "The siderophore iron transporter of Candida albicans(Sit1p", Arn1p)mediates uptake of ferrichrome-type siderophores and is required for epithelial invasion, 2002, pp.70, 5246~5255
- Ardon O, "Identification of a Candida albicans ferrichrome transporter and its characterization by expression in Saccharomyces cerevisiae", J. Biol. Chem, 276, pp.43049~43055 (2001)
- Lesuisse E, "Siderophore uptake by Candida albicans : effect of serum treatment and comparison with Saccharomyces cerevisiae", Yeast, 19, pp.329~340 (2002)
- Nevitt T, "Host iron withholding demands siderophore utilization for Candida glabrata to survive macrophage killing", PLoS Pathog, 7, pp.e1001322~ (2011)
- Lan CY, "Regulatory networks affected by iron availability in", Mol. Microbiol, 53, pp.1451~1469 (2004)
- Chen CB, "An iron homeostasis regulatory circuit with reciprocal roles in commensalism and pathogenesis", Cell Host Microbe, 10, pp.118~135 (2011)
- Lopez-Medina E, "Candida albicans inhibits Pseudomonas aeruginosa virulence through suppression of pyochelin and pyoverdine biosynthesis", PLoS Pathog, 11, pp.e1005129~ (2015)
- Tugume L, "Cryptococcal meningitis", Nat. Rev. Dis. Primers, 9, pp.62~ (2023)
- Kronstad JW, "Expanding fungal pathogenesis : Cryptococcus breaks out of the opportunistic box", Nat. Rev. Microbiol, 9, pp.193~203 (2011)
- Xue P, "Metals and the cell surface of Cryptococcus neoformans", Curr. Opin. Microbiol, 74, pp.102331~ (2023)
- Tangen KL, "The iron-and cAMP-regulated gene SIT1 influences ferrioxamine B utilization, melanization and cell wall structure in Cryptococcus neoformans", Microbiology, 153, pp.29~41 (2007)
- Do E, "A transcriptional regulatory map of iron homeostasis reveals a new control circuit for capsule formation in Cryptococcus neoformans", Genetics, 215, pp.1171~1189 (2020)
- Valdez AF, "Pathogenicity & virulence of Histoplasma capsulatum-A multifaceted organism adapted to intracellular environments", Virulence, 13, pp.1900~1919 (2022)
- Howard DH, "Hydroxamate siderophores of Histoplasma capsulatum", Infect. Immun, 68, pp.2338~2343 (2000)
- Hilty J, "Histoplasma capsulatum utilizes siderophores for intracellular iron acquisition in macrophages", Med. Mycol, 49, pp.633~642 (2011)
- Hwang LH, "SRE1 regulates iron-dependent and-independent pathways in the fungal pathogen Histoplasma capsulatum", Eukaryot. Cell, 11, pp.16~25 (2012)
- Chao LY, "Sre1, an iron-modulated GATA DNA-binding protein of iron-uptake genes in the fungal pathogen Histoplasma capsulatum", Biochemistry, 47, pp.7274~7283 (2008)
- Olivier LM, "Peroxisomal protein targeting and identification of peroxisomal targeting signals in cholesterol biosynthetic enzymes", Biochim. Biophys. Acta, 1529, pp.89~102 (2000)
- Brechting PJ, "Histoplasma capsulatum requires peroxisomes for multiple virulence functions including siderophore biosynthesis", mBio, 14, pp.e0328422~ (2023)
- Mular A, "Cyclic analogs of desferrioxamine E siderophore for 68Ga nuclear imaging : coordination chemistry and biological activity in Staphylococcus aureus", Inorg. Chem, 60, pp.17846~17857 (2021)
- Happacher I, "Fungal siderophore metabolism with a focus on Aspergillus fumigatus : impact on biotic interactions and potential translational applications", Essays Biochem, 67, pp.829~842 (2023)
- Peukert C, "Enzyme-activated, chemiluminescent siderophore-dioxetane probes enable the selective and highly sensitive detection of bacterial pathogens", Angew. Chem Int. Ed Engl, 61, pp.e202201423~ (2022)
- Franken AC, "Heme biosynthesis and its regulation : towards understanding and improvement of heme biosynthesis in filamentous fungi", Appl. Microbiol. Biotechnol, 91, pp.447~460 (2011)
- Munawar A, "Isolation and characterisation of a ferrirhodin synthetase gene from the sugarcane pathogen Fusarium sacchari", Chembiochem, 14, pp.388~394 (2013)
- Suzuki S, "Iron chelated cyclic peptide, ferrichrysin, for oral treatment of iron deficiency : solution properties and efficacy in anemic rats", Int. J. Vitam. Nutr. Res, 77, pp.13~21 (2007)
- Eisendle M, "The intracellular siderophore ferricrocin is involved in iron storage, oxidative-stress resistance, germination, and sexual development in Aspergillus nidulans", Eukaryot. Cell, 5, pp.1596~1603 (2006)
- Yamamoto S, "Structure and iron transport activity of vibrioferrin, a new siderophore of Vibrio parahaemolyticus", J. Biochem, 115, pp.868~874 (1994)
- Konetschny-Rapp S, "Staphyloferrin A : a structurally new siderophore from staphylococci", Eur. J. Biochem, 191, pp.65~74 (1990)
- Budzikiewicz H, "Microbial siderophores", Fortschr. Chem. Org. Naturst, 92, pp.1~75 (2010)
- Pollack JR, "Enterobactin, an iron transport compound from Salmonella typhimurium", Biochem. Biophys. Res. Commun, 38, pp.989~992 (1970)
- Bister B, "The structure of salmochelins : Cglucosylated enterobactins of Salmonella enterica", Biometals, 17, pp.471~481 (2004)
- Persmark M, "Isolation, characterization, and synthesis of chrysobactin, a compound with siderophore activity from Erwinia chrysanthemi", J. Biol. Chem, 264, pp.3187~3193 (1989)
- Wake A, "Siderochrome production by Yersinia pestis and its relation to virulence", Infect. Immun, 12, pp.1211~1213 (1975)
- Cox CD, "Pyochelin: novel structure of an iron-chelating growth promoter for Pseudomonas aeruginosa", Proc. Natl. Acad. Sci. USA, 78, pp.4256~4260 (1981)
- Wendenbaum S, "The structure of pyoverdine Pa, the siderophore of Pseudomonas aeruginosa", Tetrahedron. Lett, 24, pp.4877~4880 (1983)
- Francis J, "Isolation from acid-fast bacteria of a growth-factor for Mycobacterium johnei and of a precursor of phthiocol", Nature, 163, pp.365~366 (1949)
- Gibson F, "The isolation and characterization of a hydroxamic acid(aerobactin)formed by Aerobacter aerogenes 62-I", Biochim. Biophys. Acta, 192, pp.175~184 (1969)
- Actis LA, "Characterization of anguibactin, a novel siderophore from Vibrio anguillarum 775(pJM1)", J. Bacteriol, 167, pp.57~65 (1986)
- Lesuisse E, "Siderophore-mediated iron uptake in : the SIT1 gene encodes a ferrioxamine B permease that belongs to the major facilitator superfamily", Microbiology, 144, pp.3455~3462 (1998)
- Kim JH, "FgEnd1 is a putative component of the endocytic machinery and mediates ferrichrome uptake in F. graminearum", Curr. Genet, 55, pp.593~600 (2009)
- Park M, "Whole genome sequencing analysis of the cutaneous pathogenic yeast Malassezia restricta and identification of the major lipase expressed on the scalp of patients with dandruff", Mycoses, 60, pp.188~197 (2017)
- Cho YJ, "Resequencing the genome of Malassezia restricta strain KCTC 27527", Microbiol. Resour. Announc, 8, pp.e00213-19~ (2019)
- Srivastava VK, "A systematic analysis reveals an essential role for high-affinity iron uptake system, haemolysin and CFEM domain-containing protein in iron homoeostasis and virulence in Candida glabrata", Biochem. J, 463, pp.103~114 (2014)
- Wortman JR, "The 2008 update of the Aspergillus nidulans genome annotation : a community effort", Fungal Genet. Biol. 46 Suppl, 1, pp.S2~S13 (2009)
- Attarian R, "The monothiol glutaredoxin Grx4 regulates iron homeostasis and virulence in Cryptococcus neoformans", mBio, 9, pp.e02377-18~ (2018)
