Skip to main content

Advertisement

SpringerLink
Log in

Phylogenetic Diversity and In Vitro Susceptibility Profiles of Human Pathogenic Members of the Fusarium fujikuroi Species Complex Isolated from South India

  • Original Paper
  • Published:
Mycopathologia Aims and scope Submit manuscript

Abstract

Availability of molecular methods, gene sequencing, and phylogenetic species recognition have led to rare fungi being recognized as opportunistic pathogens. Fungal keratitis and onychomycosis are fairly common mycoses in the tropics, especially among outdoor workers and enthusiasts. The frequently isolated etiological agents belong to genera Candida, Aspergillus, and Fusarium. Within the genus Fusarium, known to be recalcitrant to prolonged antifungal treatment and associated with poor outcome, members of the Fusarium solani species complex are reported to be most common, followed by members of the Fusarium oxysporum SC and the Fusarium fujikuroi SC (FFSC). Morphological differentiation among the various members is ineffective most times. In the present study, we describe different species of the FFSC isolated from clinical specimen in south India. All twelve isolates were characterized up to species level by nucleic acid sequencing and phylogenetic analysis. The molecular targets chosen were partial regions of the internal transcribed spacer rDNA region, the panfungal marker and translation elongation factor-1α gene, the marker of choice for Fusarium speciation. Phylogenetic analysis was executed using the Molecular Evolutionary Genetics Analysis software (MEGA7). In vitro susceptibility testing against amphotericin B, voriconazole, posaconazole, natamycin, and caspofungin diacetate was performed following the CLSI M38-A2 guidelines for broth microdilution method. The twelve isolates of the FFSC were F. verticillioides (n = 4), F. sacchari (n = 3), F. proliferatum (n = 2), F. thapsinum (n = 1), F. andiyazi (n = 1), and F. pseudocircinatum (n = 1). To the best of our knowledge, this is the first report of F. andiyazi from India and of F. pseudocircinatum as a human pathogen worldwide. Natamycin and voriconazole were found to be most active agents followed by amphotericin B. Elderly outdoor workers figured more among the patients and must be recommended protective eye wear.

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

Similar content being viewed by others

References

  1. Gopinathan U, Garg P, Fernandes M, Sharma S, Athmanathan S, Rao GN. The epidemiological features and laboratory results of fungal keratitis. Cornea. 2002;21(6):555–9.

    Article  PubMed  Google Scholar 

  2. Tilak R, Singh A, Maurya OP, Chandra A, Tilak V, Gulati K. Mycotic keratitis in India: a five-year retrospective study. J Infect Dev Ctries. 2010;4(3):171–4.

    Article  PubMed  Google Scholar 

  3. Satpathi P, Satpathi S. Letter to the editor study of microbial keratitis in central India. J Infect Dev Ctries. 2012;6(3):295–8.

    Article  PubMed  Google Scholar 

  4. Gajjar DU, Pal AK, Ghodadra BK, Vasavada AR. Microscopic evaluation, molecular identification, antifungal susceptibility, and clinical outcomes in Fusarium, Aspergillus and dematiaceous keratitis. Biomed Res Int. 2013;2013:605308.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Tosti A, Piraccini BM, Lorenzi S. Onychomycosis caused by nondermatophytic molds: clinical features and response to treatment of 59 cases. J Am Acad Dermatol. 2000;42(2):217–24.

    Article  PubMed  CAS  Google Scholar 

  6. Zhang N, O’Donnell K, Sutton DA, Nalim FA, Summerbell RC, Padhye AA, Geiser DM. Members of the Fusarium solani species complex that cause infections in both humans and plants are common in the environment. J Clin Microbiol. 2006;44(6):2186–90.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Al-Maqtoofi M, Thornton CR. Detection of human pathogenic Fusarium species in hospital and communal sink biofilms by using a highly specific monoclonal antibody. Environ Microbiol. 2016;18(11):3620–34. https://doi.org/10.1111/1462-2920.13233.

    Article  PubMed  CAS  Google Scholar 

  8. Guarro J. Fusariosis, a complex infection caused by a high diversity of fungal species refractory to treatment. Eur J Clin Microbiol Infect Dis. 2013;32(12):1491–500.

    Article  PubMed  CAS  Google Scholar 

  9. Arrese JE, Piérard-Franchimont C, Piérard GE. Fatal hyalohyphomycosis following Fusarium onychomycosis in an immunocompromised patient. Am J Dermatopathol. 1996;18(2):196–8.

    Article  PubMed  CAS  Google Scholar 

  10. Esnakula AK, Summers I, Naab TJ. Fatal disseminated Fusarium infection in a human immunodeficiency virus positive patient. Case Rep Infect Dis. 2013. https://doi.org/10.1155/2013/379320.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Al-Hatmi AM, Hagen F, Menken SB, Meis JF, De Hoog GS. Global molecular epidemiology and genetic diversity of Fusarium, a significant emerging group of human opportunists from 1958 to 2015. Emerg Microbes Infect. 2016;5(12):e124.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Nucci M, Anaissie E. Fusarium infections in immunocompromised patients. Clin Microbiol Rev. 2007;20(4):695–704.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Taj-Aldeen SJ. Reduced multidrug susceptibility profile is a common feature of opportunistic Fusarium species: Fusarium multi-drug resistant pattern. J Fungi (Basel). 2017;3:18.

    Article  CAS  Google Scholar 

  14. Al-Hatmi AMS, Meis JF, de Hoog GS. Fusarium: molecular diversity and intrinsic drug resistance. PLoS Pathog. 2016;12(4):e1005464. https://doi.org/10.1371/journal.ppat.1005464.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. O’Donnell K, Sutton DA, Rinaldi MG, Sarver BA, Balajee SA, Schroers HJ, et al. Internet-accessible DNA sequence database for identifying fusaria from human and animal infections. J Clin Microbiol. 2010;48(10):3708–18.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Kvas M, Marasas WF. Diversity and evolution of Fusarium species in the Gibberella fujikuroi complex. Fungal Divers. 2009;34:1–21.

    Google Scholar 

  17. O’Donnell K, Cigelnik E, Nirenberg HI. Molecular systematics and phylogeography of the Gibberella fujikuroi species complex. Mycologia. 1998;90:465–93.

    Article  Google Scholar 

  18. O’Donnell K, Kistler HC, Cigelnik E, Ploetz RC. Multiple evolutionary origins of the fungus causing Panama disease of banana: concordant evidence from nuclear and mitochondrial gene genealogies. Proc Natl Acad Sci USA. 1998;95:2044–9.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Niehaus E-M, Münsterkötter M, Proctor RH, et al. Comparative “Omics” of the Fusarium fujikuroi species complex highlights differences in genetic potential and metabolite synthesis. Genome Biol Evol. 2016;8(11):3574–99. https://doi.org/10.1093/gbe/evw259.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Al-Hatmi AMS, Bonifaz A, de Hoog GS, Vazquez-Maya L, Garcia-Carmona K, Meis JF, et al. Keratitis by Fusarium temperatum, a novel opportunist. BMC Infect Dis. 2014;14(1):588.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Moroti RV, Gheorghita V, Al-Hatmi AMS, de Hoog GS, Meis JF, Netea MG. Fusarium ramigenum, a novel human opportunist in a patient with common variable immunodeficiency and cellular immune defects: case report. BMC Infect Dis. 2016;16:79. https://doi.org/10.1186/s12879-016-1382-9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. van Diepeningen AD, Al-Hatmi AMS, Brankovics B, de Hoog GS. Taxonomy and clinical spectra of Fusarium species: where do we stand in 2014? Curr Clin Microbiol Rep. 2014;1(1–2):10–8.

    Article  Google Scholar 

  23. Geiser DM, Jiménez-Gasco MDM, Kang S, Makalowska I, Veeraraghavan N, Ward TJ, et al. FUSARIUM-ID v. 1.0: a DNA sequence database for identifying Fusarium. Eur J Plant Pathol. 2004;110(5–6):473–9.

    Article  CAS  Google Scholar 

  24. Kumar S, Stecher G, Tamura K. MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol. 2016;33(7):1870–4.

    Article  PubMed  CAS  Google Scholar 

  25. Saitou N, Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 1987;4:406–25.

    PubMed  CAS  Google Scholar 

  26. Dopazo J. Estimating errors and confidence intervals for branch lengths in phylogenetic trees by a bootstrap approach. J Mol Evol. 1994;38:300–4.

    Article  PubMed  CAS  Google Scholar 

  27. Rzhetsky A, Nei M. A simple method for estimating and testing minimum evolution trees. Mol Biol Evol. 1992;9:945–67.

    CAS  Google Scholar 

  28. Tamura K, Nei M, Kumar S. Prospects for inferring very large phylogenies by using the neighbor-joining method. Proc Natl Acad Sci USA. 2004;101:11030–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Rex JH, Ghannoum MA, Alexander BD, Knapp CC, Andes D, Motyl MR, et al. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard-CLSI document M38-A2. Wayne, PA: Clinical and Laboratory Standards Institute (CLSI); 2008. p. 52.

  30. Espinel-Ingroff A, Fothergill A, Ghannoum M, Manavathu E, Ostrosky-Zeichner L, Pfaller MA, et al. Quality control and reference guidelines for CLSI broth microdilution method (M38-A document) for susceptibility testing of anidulafungin against molds. J Clin Microbiol. 2007;45(7):2180–2.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Homa M, Shobana CS, Singh YRB, Manikandan P, Selvam KP, Kredics L, et al. Fusarium keratitis in south India: causative agents, their antifungal susceptibilities and a rapid identification method for the Fusarium solani species complex. Mycoses. 2013;56(5):501–11.

    Article  PubMed  CAS  Google Scholar 

  32. Walther G, Stasch S, Kaerger K, Hamprecht A, Roth M, Cornely OA, Geerling G, Mackenzie CR, Kurzai O, von Lilienfeld-Toal M. Fusarium keratitis in Germany. J Clin Microbiol. 2017;55(10):2983–95.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Maertens JA. History of the development of azole derivatives. Clin Microbiol Infect. 2004;10(Suppl 1):1–10.

    Article  PubMed  CAS  Google Scholar 

  34. Rheeder JP, Marasas WF, Vismer HF. Production of fumonisin analogs by Fusarium species. Appl Environ Microbiol. 2002;68(5):2101–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. O’Donnell K, Cigelnik E. Two divergent intragenomic rDNA ITS2 types within a mono-phyletic lineage of the fungus Fusarium are nonorthologous. Mol Phylogenet Evol. 1997;7:103–16.

    Article  PubMed  Google Scholar 

  36. Geiser DM, Mar Jiménez-Gasco M, Kang S, Makalowska I, Veeraraghavan N, Ward TJ, Zhang N, Kuldau GA, O’Donnell K. FUSARIUM-ID v. 1.0: a DNA sequence database for identifying Fusarium. Eur J Plant Pathol. 2004;110:473–9.

    Article  CAS  Google Scholar 

  37. Al-Hatmi AMS, Van Diepeningen AD, Curfs-Breuker I, de Hoog GS, Meis JF. Specific antifungal susceptibility profiles of opportunists in the Fusarium fujikuroi complex. J Antimicrob Chemother. 2015;70(4):1068–71.

    PubMed  CAS  Google Scholar 

  38. Espinel-Ingroff A, Colombo AL, Cordoba S, Dufresne PJ, Fuller J, Ghannoum M, Gonzalez GM, Guarro J, Kidd SE, Meis JF, Melhem TM. International evaluation of MIC distributions and epidemiological cutoff value (ECV) definitions for Fusarium species identified by molecular methods for the CLSI broth microdilution method. Antimicrob Agents Chemother. 2016;60(2):1079–84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Macêdo DP, Neves RP, Fontan J, Souza-Motta CM, Lima D. A case of invasive rhinosinusitis by Fusarium verticillioides (Saccardo) Nirenberg in an apparently immunocompetent patient. Med Mycol. 2008;46(5):499–503.

    Article  PubMed  Google Scholar 

  40. Dornbusch HJ, Buzina W, Summerbell RC, Lass-Flörl C, Lackner H, Schwinger W, Sovinz P, Urban C. Fusarium verticillioides abscess of the nasal septum in an immunosuppressed child: case report and identification of the morphologically atypical fungal strain. J Clin Microbiol. 2005;43(4):1998–2001.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Collins MS, Rinaldi MG. Cutaneous infection in man caused by Fusarium moniliforme. Sabouraudia. 1977;15(2):151–60.

    Article  PubMed  CAS  Google Scholar 

  42. Cocchi S, Codeluppi M, Venturelli C, Bedini A, Grottola A, Gennari W, Cavrini F, Di Benedetto F, De Ruvo N, Rumpianesi F, Gerunda GE. Fusarium verticillioides fungemia in a liver transplantation patient: successful treatment with voriconazole. Diagn Microbiol Infect Dis. 2011;71(4):438–41.

    Article  PubMed  Google Scholar 

  43. Bansal Y, Chander J, Kaistha N, Singla N, Sood S, Diepeningen AD. Fusarium sacchari, a cause of mycotic keratitis among sugarcane farmers—a series of four cases from North India. Mycoses. 2016;59(11):705–9.

    Article  PubMed  CAS  Google Scholar 

  44. Guarro J, Nucci M, Akiti T, Gené J, Barreiro MD, Gonçalves RT. Fungemia due to Fusarium sacchari in an immunosuppressed patient. J Clin Microbiol. 2000;38(1):419–21.

    PubMed  PubMed Central  CAS  Google Scholar 

  45. Summerbell RC, Richardson SE, Kane J. Fusarium proliferatum as an agent of disseminated infection in an immunosuppressed patient. J Clin Microbiol. 1988;26(1):82–7.

    PubMed  PubMed Central  CAS  Google Scholar 

  46. Ferrer C, Alio J, Rodriguez A, Andreu M, Colom F. Endophthalmitis caused by Fusarium proliferatum. J Clin Microbiol. 2005;43(10):5372–5.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Kebabcı N, Diepeningen AD, Ener B, Ersal T, Meijer M, Al-Hatmi A, Özkocaman V, Ursavaş A, Çetinoğlu ED, Akalın H. Fatal breakthrough infection with Fusarium andiyazi: new multi-resistant aetiological agent cross-reacting with Aspergillus galactomannan enzyme immunoassay. Mycoses. 2014;57(4):249–55.

    Article  PubMed  CAS  Google Scholar 

  48. Freeman S, Otero-Colina G, Rodríguez-Alvarado G, Fernández-Pavía S, Maymon M, Ploetz RC, Aoki T, O’Donnell K. First report of mango malformation disease caused by Fusarium pseudocircinatum in Mexico. Plant Dis. 2014;98(11):1583.

    Article  Google Scholar 

Download references

Acknowledgements

This study has been funded by the Indian Council of Medical Research (ICMR), New Delhi, India, through the ICMR-TSS MD-PhD Fellowship awarded to Dr. Ananya Tupaki-Sreepurna.

Author information

Authors and Affiliations

  1. Department of Microbiology, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra University, Porur, Chennai, Tamilnadu, 600116, India

    Ananya Tupaki-Sreepurna, Vijayakishore Thanneru, Sangeetha Natarajan & Anupma Jyoti Kindo

  2. Jhaveri Microbiology Centre, LV Prasad Eye Institute, Kallam Anji Reddy Campus, L V Prasad Marg, Banjara Hills, Hyderabad, Telangana, 500034, India

    Savitri Sharma

  3. Department of Microbiology, Kempegowda Institute of Medical Sciences, Athibabbe Road, Banashankari Stage II, Banashankari, Bengaluru, Karnataka, 560070, India

    Anjana Gopi

  4. Department of Dermatology, Venereology and Leprosy, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra University, Porur, Chennai, Tamilnadu, 600116, India

    Murugan Sundaram

Authors
  1. Ananya Tupaki-Sreepurna
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vijayakishore Thanneru
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sangeetha Natarajan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Savitri Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anjana Gopi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Murugan Sundaram
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anupma Jyoti Kindo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ananya Tupaki-Sreepurna.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tupaki-Sreepurna, A., Thanneru, V., Natarajan, S. et al. Phylogenetic Diversity and In Vitro Susceptibility Profiles of Human Pathogenic Members of the Fusarium fujikuroi Species Complex Isolated from South India. Mycopathologia 183, 529–540 (2018). https://doi.org/10.1007/s11046-018-0248-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11046-018-0248-7

Keywords

Search

Navigation