Skip to main content

Advertisement

SpringerLink
Log in

Insights into the cellular responses to hypoxia in filamentous fungi

  • Research Article
  • Published:
Current Genetics Aims and scope Submit manuscript

Abstract

Most eukaryotes require molecular oxygen for growth. In general, oxygen is the terminal electron acceptor of the respiratory chain and represents an important substrate for the biosynthesis of cellular compounds. However, in their natural environment, such as soil, and also during the infection, filamentous fungi are confronted with low levels of atmospheric oxygen. Transcriptome and proteome studies on the hypoxic response of filamentous fungi revealed significant alteration of the gene expression and protein synthesis upon hypoxia. These analyses discovered not only common but also species-specific responses to hypoxia with regard to NAD+ regeneration systems and other metabolic pathways. A surprising outcome was that the induction of oxidative and nitrosative stress defenses during oxygen limitation represents a general trait of adaptation to hypoxia in many fungi. The interplay of these different stress responses is poorly understood, but recent studies have shown that adaptation to hypoxia contributes to virulence of pathogenic fungi. In this review, results on metabolic changes of filamentous fungi during adaptation to hypoxia are summarized and discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Abe T, Hoshino T, Nakamura A, Takaya N (2007) Anaerobic elemental sulfur reduction by fungus Fusarium oxysporum. Biosci Biotechnol Biochem 71:2402–2407. doi:10.1271/bbb.70083

    Article  CAS  PubMed  Google Scholar 

  • Baidya S, Cary JW, Grayburn WS, Calvo AM (2011) Role of nitric oxide and flavohemoglobin homolog genes in Aspergillus nidulans sexual development and mycotoxin production. Appl Environ Microbiol 77:5524–5528. doi:10.1128/aem.00638-11

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Barker B, Kroll K, Vodisch M, Mazurie A, Kniemeyer O, Cramer R (2012) Transcriptomic and proteomic analyses of the Aspergillus fumigatus hypoxia response using an oxygen-controlled fermenter. BMC Genom 13:62. doi:10.1186/1471-2164-13-62

    Article  CAS  Google Scholar 

  • Berchner-Pfannschmidt U, Yamac H, Trinidad B, Fandrey J (2007) Nitric oxide modulates oxygen sensing by Hypoxia-inducible Factor 1-dependent induction of prolyl hydroxylase 2. J Biol Chem 282:1788–1796. doi:10.1074/jbc.M607065200

    Article  CAS  PubMed  Google Scholar 

  • Blatzer M, Barker BM, Willger SD, Beckmann N, Blosser SJ, Cornish EJ, Mazurie A, Grahl N, Haas H, Cramer RA (2011) SREBP coordinates iron and ergosterol homeostasis to mediate triazole drug and hypoxia responses in the human fungal pathogen Aspergillus fumigatus. PLoS Genet 7:e1002374. doi:10.1371/journal.pgen.1002374

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bonaccorsi ED, Ferreira AJ, Chambergo FS, Ramos AS, Mantovani MC, Farah JP, Sorio CS, Gombert AK, Tonso A, El-Dorry H (2006) Transcriptional response of the obligatory aerobe Trichoderma reesei to hypoxia and transient anoxia: implications for energy production and survival in the absence of oxygen. Biochemistry 45:3912–3924. doi:10.1021/bi052045o

    Article  CAS  PubMed  Google Scholar 

  • Brakhage AA, Bruns S, Thywissen A, Zipfel PF, Behnsen J (2010) Interaction of phagocytes with filamentous fungi. Curr Opin Microbiol 13:409–415. doi:10.1016/j.mib.2010.04.009

    Article  CAS  PubMed  Google Scholar 

  • Burke PV, Poyton RO (1998) Structure/function of oxygen-regulated isoforms in cytochrome c oxidase. J Exp Biol 201:1163–1175

    CAS  PubMed  Google Scholar 

  • Castello PR, David PS, McClure T, Crook Z, Poyton RO (2006) Mitochondrial cytochrome oxidase produces nitric oxide under hypoxic conditions: implications for oxygen sensing and hypoxic signalling in eukaryotes. Cell Metab 3:277–287. doi:10.1016/j.cmet.2006.02.011

    Article  CAS  PubMed  Google Scholar 

  • Chandel NS, Budinger GRS (2007) The cellular basis for diverse responses to oxygen. Free Radic Biol Med 42:165–174. doi:10.1016/j.freeradbiomed.2006.10.048

    Article  CAS  PubMed  Google Scholar 

  • Chowdhury R, Godoy LC, Thiantanawat A, Trudel LJ, Deen WM, Wogan GN (2012) Nitric oxide produced endogenously is responsible for Hypoxia-Induced HIF-1α stabilization in colon carcinoma cells. Chem Res Toxicol 25:2194–2202. doi:10.1021/tx300274a

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chun CD, Liu OW, Madhani HD (2007) A link between virulence and homeostatic responses to hypoxia during infection by the human fungal pathogen Cryptococcus neoformans. PLoS Pathog 3:e22. doi:10.1371/journal.ppat.0030022

    Article  PubMed Central  PubMed  Google Scholar 

  • Chung D, Barker BM, Carey CC, Merriman B, Werner ER, Lechner BE, Dhingra S, Cheng C, Xu W, Blosser SJ, Morohashi K, Mazurie A, Mitchell TK, Haas H, Mitchell AP, Cramer RA (2014) ChIP-seq and in vivo transcriptome analyses of the Aspergillus fumigatus SREBP SrbA reveals a new regulator of the fungal hypoxia response and virulence. PLoS Pathog 10:e1004487. doi:10.1371/journal.ppat.1004487

    Article  PubMed Central  PubMed  Google Scholar 

  • Cramer R, Fedorova ND, Pakala S, Pakala S, Joadar V, Barker B, Nierman WC (2013) Aspergillus fumigatus transcriptome under normoxia and hypoxia conditions. GEO accession GSE30579 (http://www.ncbi.nlm.nih.gov/geo/)

  • Cussler EL (1997) Diffusion: mass transfer in fluid systems, 2nd edn. Cambridge University Press, New York

    Google Scholar 

  • Dagenais TRT, Keller NP (2009) Pathogenesis of Aspergillus fumigatus in invasive aspergillosis. Clin Microbiol Rev 22:447–465. doi:10.1128/cmr.00055-08

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Diano A, Peeters J, Dynesen J, Nielsen J (2009) Physiology of Aspergillus niger in oxygen-limited continuous cultures: influence of aeration, carbon source concentration and dilution rate. Biotechnol Bioeng 103:956–965. doi:10.1002/bit.22329

    Article  CAS  PubMed  Google Scholar 

  • Dirmeier R, O’Brien KM, Engle M, Dodd A, Spears E, Poyton RO (2002) Exposure of yeast cells to anoxia induces transient oxidative stress: implications for the induction of hypoxic genes. J Biol Chem 277:34773–34784. doi:10.1074/jbc.M203902200

    Article  CAS  PubMed  Google Scholar 

  • Durrant LR, Canale-Parola E, Leschine SB (1995) Facultatively anaerobic cellulolytic fungi from soil. In: Collins HP, Robertson GP, Klug MJ (eds) The significance and regulation of soil biodiversity (developments in plant and soil sciences). Springer, Netherlands, pp 161–167

    Chapter  Google Scholar 

  • Eberle D, Hegarty B, Bossard P, Ferre P, Foufelle F (2004) SREBP transcription factors: master regulators of lipid homeostasis. Biochimie 86:839–848

    Article  CAS  PubMed  Google Scholar 

  • Formenti F, Constantin-Teodosiu D, Emmanuel Y, Cheeseman J, Dorrington KL, Edwards LM, Humphreys SM, Lappin TRJ, McMullin MF, McNamara CJ, Mills W, Murphy JA, O’Connor DF, Percy MJ, Ratcliffe PJ, Smith TG, Treacy M, Frayn KN, Greenhaff PL, Karpe F, Clarke K, Robbins PA (2010) Regulation of human metabolism by hypoxia-inducible factor. Proc Natl Acad Sci 107:12722–12727. doi:10.1073/pnas.1002339107

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fröhlich A, Durner J (2011) The hunt for plant nitric oxide synthase (NOS): is one really needed? Plant Sci 181:401–404. doi:10.1016/j.plantsci.2011.07.014

    Article  PubMed  Google Scholar 

  • Fukuda R, Zhang H, J-w Kim, Shimoda L, Dang CV, Semenza Gregg L (2007) HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. Cell 129:111–122. doi:10.1016/j.cell.2007.01.047

    Article  CAS  PubMed  Google Scholar 

  • Gardner PR, Gardner AM, Martin LA, Salzman AL (1998) Nitric oxide dioxygenase: an enzymic function for flavohemoglobin. Proc Natl Acad Sci USA 95:10378–10383

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ghillebert R, Swinnen E, Wen J, Vandesteene L, Ramon M, Norga K, Rolland F, Winderickx J (2011) The AMPK/SNF1/SnRK1 fuel gauge and energy regulator: structure, function and regulation. FEBS J 278:3978–3990

    Article  CAS  PubMed  Google Scholar 

  • Gómez Sánchez CE, Martínez-Trujillo A, Aguilar Osorio G (2012) Oxygen transfer coefficient and the kinetic parameters of exo-polygalacturonase production by Aspergillus flavipes FP-500 in shake flasks and bioreactor. Lett Appl Microbiol 55:444–452. doi:10.1111/j.1472-765x.2012.03313.x

    PubMed  Google Scholar 

  • Gostincar C, Grube M, de Hoog S, Zalar P, Gunde-Cimerman N (2010) Extremotolerance in fungi: evolution on the edge. FEMS Microbiol Ecol 71:2–11. doi:10.1111/j.1574-6941.2009.00794.x

    Article  CAS  PubMed  Google Scholar 

  • Grahl N, Puttikamonkul S, Macdonald JM, Gamcsik MP, Ngo LY, Hohl TM, Cramer RA (2011) In vivo hypoxia and a fungal alcohol dehydrogenase influence the pathogenesis of invasive pulmonary aspergillosis. PLoS Pathog 7:e1002145. doi:10.1371/journal.ppat.1002145

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Grahl N, Dinamarco TM, Willger SD, Goldman GH, Cramer RA (2012a) Aspergillus fumigatus mitochondrial electron transport chain mediates oxidative stress homeostasis, hypoxia responses and fungal pathogenesis. Mol Microbiol 84:383–399. doi:10.1111/j.1365-2958.2012.08034.x

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Grahl N, Shepardson KM, Chung D, Cramer RA (2012b) Hypoxia and fungal pathogenesis: to air or not to air? Eukaryot Cell 11:560–570. doi:10.1128/ec.00031-12

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gunner HB, Alexander M (1964) Anaerobic growth of Fusarium oxysporum. J Bacteriol 87:1309–1316

    CAS  PubMed Central  PubMed  Google Scholar 

  • Guzy RD, Hoyos B, Robin E, Chen H, Liu L, Mansfield KD, Simon MC, Hammerling U, Schumacker PT (2005) Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing. Cell Metab 1:401–408. doi:10.1016/j.cmet.2005.05.001

    Article  CAS  PubMed  Google Scholar 

  • Gyamerah MH (1995) Oxygen requirement and energy relations of itaconic acid fermentation by Aspergillus terreus NRRL 1960. Appl Microbiol Biotechnol 44:20–26. doi:10.1007/bf00164475

    Article  Google Scholar 

  • Hall LA, Denning DW (1994) Oxygen requirements of Aspergillus species. J Med Microbiol 41:311–315. doi:10.1099/00222615-41-5-311

    Article  CAS  PubMed  Google Scholar 

  • Hanslin HM, Sæb A, Bergersen O (2005) Estimation of oxygen concentration in the soil gas phase beneath compost mulch by means of a simple method. Urban For Urban Green 4:37–40. doi:10.1016/j.ufug.2005.05.001

    Article  Google Scholar 

  • Henriet SSV, Hermans PWM, Verweij PE, Simonetti E, Holland SM, Sugui JA, Kwon-Chung KJ, Warris A (2011) Human leukocytes kill Aspergillus nidulans by reactive oxygen species-independent mechanisms. Infect Immun 79:767–773. doi:10.1128/iai.00921-10

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hillmann F, Linde J, Beckmann N, Cyrulies M, Strassburger M, Heinekamp T, Haas H, Guthke R, Kniemeyer O, Brakhage AA (2014) The novel globin protein fungoglobin is involved in low oxygen adaptation of Aspergillus fumigatus. Mol Microbiol 93:539–553. doi:10.1111/mmi.12679

    Article  CAS  PubMed  Google Scholar 

  • Hofmann G, Diano A, Nielsen J (2009) Recombinant bacterial hemoglobin alters metabolism of Aspergillus niger. Metab Eng 11:8–12. doi:10.1016/j.ymben.2008.07.002

    Article  CAS  PubMed  Google Scholar 

  • Hsu JL, Khan MA, Sobel RA, Jiang X, Clemons KV, Nguyen TT, Stevens DA, Martinez M, Nicolls MR (2013) Aspergillus fumigatus invasion increases with progressive airway ischemia. PLoS ONE 8:e77136. doi:10.1371/journal.pone.0077136

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hughes AL, Todd BL, Espenshade PJ (2005) SREBP pathway responds to sterols and functions as an oxygen sensor in fission yeast. Cell 120:831–842

    Article  CAS  PubMed  Google Scholar 

  • Jiang X, Hsu J, Tian W, Yuan K, Olcholski M, de Jesus Perez V, Semenza G, Nicolls M (2013) Tie2-dependent VHL knockdown promotes airway microvascular regeneration and attenuates invasive growth of Aspergillus fumigatus. J Mol Med 91:1081–1093. doi:10.1007/s00109-013-1063-8

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kaya M, Matsumura K, Higashida K, Hata Y, Kawato A, Abe Y, Akita O, Takaya N, Shoun H (2004) Cloning and enhanced expression of the cytochrome P450nor gene (nicA; CYP55A5) encoding nitric oxide reductase from Aspergillus oryzae. Biosci Biotechnol Biochem 68:2040–2049. doi:10.1271/bbb.68.2040

    Article  CAS  PubMed  Google Scholar 

  • Kroll K, Pähtz V, Hillmann F, Vaknin Y, Schmidt-Heck W, Roth M, Jacobsen ID, Osherov N, Brakhage AA, Kniemeyer O (2014) Identification of hypoxia-inducible target genes of Aspergillus fumigatus by transcriptome analysis reveals cellular respiration as important contributor to hypoxic survival. Eukaryot Cell. doi:10.1128/ec.00084-14

    PubMed Central  PubMed  Google Scholar 

  • Kurakov AV, Khidirov KS, Sadykova VS, Zviagintsev DG (2011) Anaerobic growth ability and alcohol fermentation activity of microscopic fungi. Prikl Biokhim Mikrobiol 47:187–193

    CAS  PubMed  Google Scholar 

  • Lapp K, Vödisch M, Kroll K, Strassburger M, Kniemeyer O, Heinekamp T, Brakhage AA (2014) Characterization of the Aspergillus fumigatus detoxification systems for reactive nitrogen intermediates and their impact on virulence. Front Microbiol 5:469. doi:10.3389/fmicb.2014.00469

    Article  PubMed Central  PubMed  Google Scholar 

  • Lara-Ortíz T, Riveros-Rosas H, Aguirre J (2003) Reactive oxygen species generated by microbial NADPH oxidase NoxA regulate sexual development in Aspergillus nidulans. Mol Microbiol 50:1241–1255. doi:10.1046/j.1365-2958.2003.03800.x

    Article  PubMed  Google Scholar 

  • Lessing F, Kniemeyer O, Wozniok I, Loeffler J, Kurzai O, Haertl A, Brakhage AA (2007) The Aspergillus fumigatus transcriptional regulator AfYap1 represents the major regulator for defense against reactive oxygen intermediates but is dispensable for pathogenicity in an intranasal mouse infection model. Eukaryot Cell 6:2290–2302. doi:10.1128/ec.00267-07

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Liggenstoffer AS, Youssef NH, Couger MB, Elshahed MS (2010) Phylogenetic diversity and community structure of anaerobic gut fungi (phylum Neocallimastigomycota) in ruminant and non-ruminant herbivores. ISME J 4:1225–1235. doi:10.1038/ismej.2010.49

    Article  PubMed  Google Scholar 

  • Lin Y-H, Li Y-F, Huang M-C, Tsai Y-C (2004) Intracellular expression of Vitreoscilla hemoglobin in Aspergillus terreus to alleviate the effect of a short break in aeration during culture. Biotechnol Lett 26:1067–1072. doi:10.1023/B:BILE.0000032964.15178.7c

    Article  CAS  PubMed  Google Scholar 

  • Losada L, Barker BM, Pakala S, Pakala S, Joardar V, Zafar N, Mounaud S, Fedorova N, Nierman WC, Cramer RA (2014) Large-scale transcriptional response to hypoxia in Aspergillus fumigatus observed using RNAseq identifies a novel hypoxia regulated ncRNA. Mycopathologia 5:5. doi:10.1007/s11046-014-9779-8

    Google Scholar 

  • Magnani T, Soriani F, Martins V, Policarpo A, Sorgi C, Faccioli L, Curti C, Uyemura S (2008) Silencing of mitochondrial alternative oxidase gene of Aspergillus fumigatus enhances reactive oxygen species production and killing of the fungus by macrophages. J Bioenerg Biomembr 40:631–636. doi:10.1007/s10863-008-9191-5

    Article  CAS  PubMed  Google Scholar 

  • Masuo S, Terabayashi Y, Shimizu M, Fujii T, Kitazume T, Takaya N (2010) Global gene expression analysis of Aspergillus nidulans reveals metabolic shift and transcription suppression under hypoxia. Mol Genet Genomics 284:415–424. doi:10.1007/s00438-010-0576-x

    Article  CAS  PubMed  Google Scholar 

  • Maxwell DP, Wang Y, McIntosh L (1999) The alternative oxidase lowers mitochondrial reactive oxygen production in plant cells. Proc Natl Acad Sci 96:8271–8276. doi:10.1073/pnas.96.14.8271

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • McCormick A, Jacobsen ID, Broniszewska M, Beck J, Heesemann J, Ebel F (2012) The two-component sensor kinase TcsC and its role in stress resistance of the human-pathogenic mold Aspergillus fumigatus. PLoS ONE 7:e38262. doi:10.1371/journal.pone.0038262

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • McDonald AE, Vanlerberghe GC (2004) Branched mitochondrial electron transport in the Animalia: presence of alternative oxidase in several Animal phyla. IUBMB Life 56:333–341. doi:10.1080/1521-6540400000876

    Article  CAS  PubMed  Google Scholar 

  • Michaliszyn E, Sénéchal S, Martel P, de Repentigny L (1995) Lack of involvement of nitric oxide in killing of Aspergillus fumigatus conidia by pulmonary alveolar macrophages. Infect Immun 63:2075–2078

    CAS  PubMed Central  PubMed  Google Scholar 

  • Moroz LL, Kohn AB (2007) On the comparative biology of Nitric Oxide (NO) synthetic pathways: parallel evolution of NO-mediated signalling. In: Bruno T, Barry T (eds) Nitric oxide. Advances in experimental biology, vol 1. Elsevier Science & Technology, Amsterdam, Oxford, pp 1–44

  • Müller M, Mentel M, van Hellemond JJ, Henze K, Woehle C, Gould SB, Yu RY, van der Giezen M, Tielens AG, Martin WF (2012) Biochemistry and evolution of anaerobic energy metabolism in eukaryotes. Microbiol Mol Biol Rev 76:444–495. doi:10.1128/MMBR.05024-11

    Article  PubMed Central  PubMed  Google Scholar 

  • Mustroph A, Lee SC, Oosumi T, Zanetti ME, Yang H, Ma K, Yaghoubi-Masihi A, Fukao T, Bailey-Serres J (2010) Cross-kingdom comparison of transcriptomic adjustments to low-oxygen stress highlights conserved and plant-specific responses. Plant Physiol 152:1484–1500. doi:10.1104/pp.109.151845

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nakanishi Y, Zhou S, Kim SW, Fushinobu S, Maruyama J, Kitamoto K, Wakagi T, Shoun H (2010) A eukaryotic copper-containing nitrite reductase derived from a NirK homolog gene of Aspergillus oryzae. Biosci Biotechnol Biochem 74:984–991. doi:10.1271/bbb.90844

    Article  CAS  PubMed  Google Scholar 

  • Oostra J, le Comte EP, van den Heuvel JC, Tramper J, Rinzema A (2001) Intra-particle oxygen diffusion limitation in solid-state fermentation. Biotechnol Bioeng 75:13–24. doi:10.1002/bit.1159

    Article  CAS  PubMed  Google Scholar 

  • Panagiotou G, Christakopoulos P, Grotkjaer T, Olsson L (2006) Engineering of the redox imbalance of Fusarium oxysporum enables anaerobic growth on xylose. Metab Eng 8:474–482. doi:10.1016/j.ymben.2006.04.004

    Article  CAS  PubMed  Google Scholar 

  • Philippe B, Ibrahim-Granet O, Prévost MC, Gougerot-Pocidalo MA, Sanchez Perez M, Van der Meeren A, Latgé JP (2003) Killing of Aspergillus fumigatus by alveolar macrophages is mediated by reactive oxidant intermediates. Infect Immun 71:3034–3042. doi:10.1128/iai.71.6.3034-3042.2003

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rahardjo YS, Weber FJ, le Comte EP, Tramper J, Rinzema A (2002) Contribution of aerial hyphae of Aspergillus oryzae to respiration in a model solid-state fermentation system. Biotechnol Bioeng 78:539–544. doi:10.1002/bit.10222

    Article  PubMed  Google Scholar 

  • Rosenfeld E, Beauvoit B, Blondin B, Salmon J-M (2003) Oxygen consumption by anaerobic Saccharomyces cerevisiae under enological conditions: effect on fermentation kinetics. Appl Environ Microbiol 69:113–121. doi:10.1128/aem.69.1.113-121.2003

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ruepp A, Zollner A, Maier D, Albermann K, Hani J, Mokrejs M, Tetko I, Guldener U, Mannhaupt G, Munsterkotter M, Mewes HW (2004) The FunCat, a functional annotation scheme for systematic classification of proteins from whole genomes. Nucleic Acids Res 32:5539–5545

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Schinko T, Berger H, Lee W, Gallmetzer A, Pirker K, Pachlinger R, Buchner I, Reichenauer T, Guldener U, Strauss J (2010) Transcriptome analysis of nitrate assimilation in Aspergillus nidulans reveals connections to nitric oxide metabolism. Mol Microbiol 78:720–738. doi:10.1111/j.1365-2958.2010.07363.x

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Semenza GL (2007) Oxygen-dependent regulation of mitochondrial respiration by hypoxia-inducible factor 1. Biochem J 405:1–9. doi:10.1042/bj20070389

    CAS  PubMed  Google Scholar 

  • Shepardson KM, Ngo LY, Aimanianda V, Latge JP, Barker BM, Blosser SJ, Iwakura Y, Hohl TM, Cramer RA (2013) Hypoxia enhances innate immune activation to Aspergillus fumigatus through cell wall modulation. Microbes Infect 15:259–269. doi:10.1016/j.micinf.2012.11.010

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Shepardson KM, Jhingran A, Caffrey A, Obar JJ, Suratt BT, Berwin BL, Hohl TM, Cramer RA (2014) Myeloid derived hypoxia inducible factor 1-alpha is required for protection against pulmonary Aspergillus fumigatus infection. PLoS Pathog 10:e1004378. doi:10.1371/journal.ppat.1004378

    Article  PubMed Central  PubMed  Google Scholar 

  • Shimizu M, Takaya N (2013) Nudix hydrolase controls nucleotides and glycolytic mechanisms in hypoxic Aspergillus nidulans. Biosci Biotechnol Biochem 77:1888–1893. doi:10.1271/bbb.130334

    Article  CAS  PubMed  Google Scholar 

  • Shimizu M, Fujii T, Masuo S, Fujita K, Takaya N (2009) Proteomic analysis of Aspergillus nidulans cultured under hypoxic conditions. Proteomics 9:7–19. doi:10.1002/pmic.200701163

    Article  CAS  PubMed  Google Scholar 

  • Shimizu M, Fujii T, Masuo S, Takaya N (2010) Mechanism of de novo branched-chain amino acid synthesis as an alternative electron sink in hypoxic Aspergillus nidulans cells. Appl Environ Microbiol 76:1507–1515. doi:10.1128/aem.02135-09

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Shoun H, Tanimoto T (1991) Denitrification by the fungus Fusarium oxysporum and involvement of cytochrome P-450 in the respiratory nitrite reduction. J Biol Chem 266:11078–11082

    CAS  PubMed  Google Scholar 

  • Tabak HH, Cooke WB (1968) Growth and metabolism of fungi in an atmosphere of nitrogen. Mycologia 60:115–140. doi:10.2307/3757319

    Article  CAS  PubMed  Google Scholar 

  • Takasaki K, Shoun H, Yamaguchi M, Takeo K, Nakamura A, Hoshino T, Takaya N (2004) Fungal ammonia fermentation, a novel metabolic mechanism that couples the dissimilatory and assimilatory pathways of both nitrate and ethanol: role of acetyl CoA synthetase in anaerobic ATP synthesis. J Biol Chem 279:12414–12420. doi:10.1074/jbc.M313761200

    Article  CAS  PubMed  Google Scholar 

  • Taubitz A, Bauer B, Heesemann J, Ebel F (2007) Role of respiration in the germination process of the pathogenic mold Aspergillus fumigatus. Curr Microbiol 54:354–360. doi:10.1007/s00284-006-0413-y

    Article  CAS  PubMed  Google Scholar 

  • te Biesebeke R, Boussier A, van Biezen N, Braaksma M, van den Hondel CAMJJ, de Vos WM, Punt PJ (2006) Expression of Aspergillus hemoglobin domain activities in Aspergillus oryzae grown on solid substrates improves growth rate and enzyme production. Biotechnol J 1:822–827. doi:10.1002/biot.200600036

    Article  Google Scholar 

  • Terabayashi Y, Shimizu M, Kitazume T, Masuo S, Fujii T, Takaya N (2012) Conserved and specific responses to hypoxia in Aspergillus oryzae and Aspergillus nidulans determined by comparative transcriptomics. Appl Microbiol Biotechnol 93:305–317. doi:10.1007/s00253-011-3767-4

    Article  PubMed  Google Scholar 

  • Via LE, Lin PL, Ray SM, Carrillo J, Allen SS, Eum SY, Taylor K, Klein E, Manjunatha U, Gonzales J, Lee EG, Park SK, Raleigh JA, Cho SN, McMurray DN, Flynn JL, Barry CE (2008) Tuberculous granulomas are hypoxic in guinea pigs, rabbits, and nonhuman primates. Infect Immun 76:2333–2340. doi:10.1128/iai.01515-07

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Visser W, Scheffers WA, Batenburg-van der Vegte WH, van Dijken JP (1990) Oxygen requirements of yeasts. Appl Environ Microbiol 56:3785–3792

    CAS  PubMed Central  PubMed  Google Scholar 

  • Vödisch M, Scherlach K, Winkler R, Hertweck C, Braun H-P, Roth M, Haas H, Werner ER, Brakhage AA, Kniemeyer O (2011) Analysis of the Aspergillus fumigatus proteome reveals metabolic changes and the activation of the Pseurotin A biosynthesis gene cluster in response to hypoxia. J Proteome Res 10:2508–2524. doi:10.1021/pr1012812

    Article  PubMed Central  PubMed  Google Scholar 

  • Wang L, Ridgway D, Gu T, Moo-Young M (2005) Bioprocessing strategies to improve heterologous protein production in filamentous fungal fermentations. Biotech Adv 23:115–129. doi:10.1016/j.biotechadv.2004.11.001

    Article  CAS  Google Scholar 

  • Wezensky SJ, Cramer RA (2011) Implications of hypoxic microenvironments during invasive aspergillosis. Med Mycol 49:S120–S124. doi:10.3109/13693786.2010.495139

    Article  PubMed Central  PubMed  Google Scholar 

  • Willger SD, Puttikamonkul S, Kim K-H, Burritt JB, Grahl N, Metzler LJ, Barbuch R, Bard M, Lawrence CB, Cramer RA Jr (2008) A Sterol-regulatory element binding protein is required for cell polarity, hypoxia adaptation, azole drug resistance, and virulence in Aspergillus fumigatus. PLoS Pathog 4:e1000200. doi:10.1371/journal.ppat.1000200

    Article  PubMed Central  PubMed  Google Scholar 

  • Zhou Z, Takaya N, Nakamura A, Yamaguchi M, Takeo K, Shoun H (2002) Ammonia fermentation, a novel anoxic metabolism of nitrate by fungi. J Biol Chem 277:1892–1896. doi:10.1074/jbc.M109096200

    Article  CAS  PubMed  Google Scholar 

  • Zhou Z, Takaya N, Shoun H (2010) Multi-energy metabolic mechanisms of the fungus Fusarium oxysporum in low oxygen environments. Biosci Biotechnol Biochem 74:2431–2437. doi:10.1271/bbb.100482

    Article  CAS  PubMed  Google Scholar 

  • Zhou S, Fushinobu S, Kim SW, Nakanishi Y, Maruyama J, Kitamoto K, Wakagi T, Shoun H (2011) Functional analysis and subcellular location of two flavohemoglobins from Aspergillus oryzae. Fungal Genet Biol 48:200–207. doi:10.1016/j.fgb.2010.08.011

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Work in the authors’ lab was supported by funding from the Leibniz-Association, the International Leibniz Research School (ILRS) for Microbial and Biomolecular Interactions as part of the DFG-funded excellence graduate school Jena School for Microbial Communication (JSMC), the German-Israeli Foundation for Scientific Research and Development (GIF No. 996-47.12/2008), and the ERA-Net Pathogenomics project “OXYstress” (BMBF project number 0315902B). We wish to thank Alene Alder-Rangel who helped to improve this manuscript. This review article was supported in part by a grant from State of São Paulo Research Foundation (FAPESP)# 2014/01229-4.

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute (HKI), Adolf-Reichwein-Str. 23, 07745, Jena, Germany

    Falk Hillmann, Elena Shekhova & Olaf Kniemeyer

  2. Institute of Microbiology, Friedrich Schiller University, Philosophenweg 12, 07743, Jena, Germany

    Falk Hillmann, Elena Shekhova & Olaf Kniemeyer

  3. Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), University Hospital, Erlanger Allee 101, 07747, Jena, Germany

    Olaf Kniemeyer

Authors
  1. Falk Hillmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elena Shekhova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Olaf Kniemeyer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Olaf Kniemeyer.

Additional information

Communicated by D.E.N. Rangel.

This article is part of the Special Issue “Fungal Stress Responses”.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hillmann, F., Shekhova, E. & Kniemeyer, O. Insights into the cellular responses to hypoxia in filamentous fungi. Curr Genet 61, 441–455 (2015). https://doi.org/10.1007/s00294-015-0487-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00294-015-0487-9

Keywords

Search

Navigation