In vitro enrichment of trace elements promotes rapid germination of Aspergillus conidia: a clinical concern for immunosuppressed and hyperglycemic patients

Document Type : Original Articles

Authors

1 Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India 221005

2 Department of Chemistry, Indian Institute of Technology, BHU, Varanasi, India 221005

3 Department of Microbiology, Institute of Medical Science, BHU, Varanasi, India

4 Department of Respiratory Medicine, Sir Sunder Lal Hospital, Varanasi, India 221005

10.22034/cmm.2024.345251.1549

Abstract

Background and Purpose: Trace elements play crucial roles in metabolic processes and serve as cofactors for various enzymes, although their specific involvement in fungal pathogenesis remains unclear. This study aimed to explore the impact of essential trace elements, iron (Fe), manganese (Mn), zinc (Zn), and copper (Cu), in conjunction with D-dextrose, on conidial germination and growth of Aspergillus fumigatus and A. flavus.
Materials and Methods: The research involved determining the minimum inhibitory concentrations (MIC) of Fe, Mn, Zn, and Cu for Aspergillus ATCC strains. The study commenced by determining the MIC of the four trace elements, followed by evaluating the impact of selected trace elements on the kinetic growth and germination rates of Aspergillus species by the micro-broth method. Following MIC assessment, optimized concentrations of the trace elements (~140 and 550 pM) and various concentrations of D-dextrose (1-3% w/v) were introduced to assess their effects on fungal growth in RPMI 1640 broth. Growth was measured in optical density, while conidial germination rates were also observed.
Results: The MICs for Fe, Mn, and Zn exceeded 35 µM, while Cu exhibited lower MICs of 2 and 7.6 µM against A. fumigatus and A. flavus, respectively. Fe, Mn, Zn, and Cu significantly enhanced fungal growth in both Aspergillus species at optimized concentrations. Additionally, growth rates increased proportionally with higher D-dextrose concentrations. Notably, combining enriched trace elements and D-dextrose resulted in up to 98% conidial germination.
Conclusion: The findings demonstrate that optimized concentrations of essential trace elements and D-dextrose significantly promote conidial germination and growth of Aspergillus species in vitro. These results suggest that trace element supplementation might have important implications for immunocompromised and hyperglycemic patients. Further studies are warranted to explore the interactions between these micronutrients in fungal physiology and pathogenesis.

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References

  1. Van De Veerdonk FL, Gresnigt MS, Romani L, Netea MG, Latgé JP. Aspergillus fumigatus morphology and dynamic host interactions. Nat Rev Microbiol. 2017;15(11):661–74.
  2. Agarwal R. Severe Asthma with Fungal Sensitization. Curr Allergy Asthma Rep. 2011;11(5):403–13.
  3. Nieder R, Benbi DK, Reichl FX. Microelements and Their Role in Human Health. In: Soil Components and Human Health. Soil components and human health. 2018:317–74.
  4. Haase H. Innate Immune Cells Speak Manganese. Immunity. 2018;48(4):616–8.
  5. Mercer JFB. The molecular basis of copper-transport diseases. Trends Mol Med. 2001;7(2):64–9.
  6. Aschner JL, Aschner M. Nutritional aspects of manganese homeostasis. Mol Aspects Med. 2005;26(4–5):353–62.
  7. Zhao D, Huang Y, Wang B, Chen H, Pan W, Yang M, et al. Dietary Intake Levels of Iron, Copper, Zinc, and Manganese in Relation to Cognitive Function: A Cross-Sectional Study. Nutrients. 2023;15(3):704.
  8. Dilworth L, Facey A, Omoruyi F. Diabetes Mellitus and Its Metabolic Complications: The Role of Adipose Tissues. Int J Mol Sci. 2021; 22(14):7644.
  9. Asrani P, Eapen MS, Hassan MI, Sohal SS. Implications of the second wave of COVID-19 in India. Lancet Respir Med. 2021;9(9):e93–4.
  10. Dimopoulos G, Almyroudi MP, Myrianthefs P, Rello J. COVID-19-Associated Pulmonary Aspergillosis (CAPA). J Intensive Med. 2021;1(2):71–80.
  11. Dilek A, Ozaras R, Ozkaya S, Sunbul M, Sen EI, Leblebicioglu H. COVID-19-associated mucormycosis: Case report and systematic review. Travel Med Infect Dis. 2021;44:102148.
  12. Gizaw A, Marami LM, Teshome I, Sarba EJ, Admasu P, Babele DA, et al. Phytochemical Screening and In Vitro Antifungal Activity of Selected Medicinal Plants against Candida albicans and Aspergillus niger in West Shewa Zone, Ethiopia. Adv Pharmacol Pharm Sci. 2022;2022:3299146.
  13. Walker GM, White NA. Introduction to fungal physiology. Fungi: biology and applications. 2017:1-35.
  14. Prashanth L, Kattapagari KK, Chitturi RT, Baddam VR, Prasad LK. A review on role of essential trace elements in health and disease. Journal of Dr. YSR University of Health Sciences. 2015;4(2):75-85.
  15. Ehrlich HL. How microbes influence mineral growth and dissolution. Chem Geol. 1996;132(1–4):5–9.
  16. Sephton-Clark PC, Voelz K. Spore Germination of Pathogenic Filamentous Fungi. Adv Appl Microbiol. 2018;102:117-57.
  17. Braunsdorf C, Mailänder-Sánchez D, Schaller M. Fungal sensing of host environment: Fungal sensing. Cell Microbiol. 2016;18(9):1188–200.
  18. Dharmalingam K, Birdi A, Tomo S, Sreenivasulu K, Charan J, Yadav D, et al. Trace Elements as Immunoregulators in SARS-CoV-2 and Other Viral Infections. Indian J Clin Biochem. 2021,36(4):416–26.
  19. Bystrom LM, Guzman ML, Rivella S. Iron and Reactive Oxygen Species: Friends or Foes of Cancer Cells? Antioxid Redox Signal. 2014;20(12):1917–24.
  20. Hissen AH, Chow JM, Pinto LJ, Moore MM. Survival of Aspergillus fumigatus in Serum Involves Removal of Iron from Transferrin: the Role of Siderophores. Infect Immun. 2004;72(3):1402–8.
  21. Chakravarty J, Gupta MK, Tilak R, Kumar R, Maurya RP, Kumar N, et al. COVID-19-associated Mucormycosis: A clinico-epidemiological study. J Diabetes Complications. 2022;36(9):
  22. Schrettl M, Haas H. Iron homeostasis—Achilles’ heel of Aspergillus fumigatus? Curr Opin Microbiol. 2011;14(4):400–5.
  23. Wu Q, Mu Q, Xia Z, Min J, Wang F. Manganese homeostasis at the host-pathogen interface and in the host immune system. Semin Cell Dev Biol. 2021;115:45–53.
  24. Nakashige TG, Zhang B, Krebs C, Nolan EM. Human calprotectin is an iron-sequestering host-defense protein. Nat Chem Biol. 2015;11(10):765–71.
  25. Balamtekin N, Kurekci AE, Atay A, Kalman S, Okutan V, Gokcay E, et al. Plasma Levels of Trace Elements Have an Implication on Interferon Treatment of Children with Chronic Hepatitis B Infection. Biol Trace Elem Res. 2010;135(1–3):153–61.
  26. Seo H, Kang S, Park YS, Yun CW. The Role of Zinc in Gliotoxin Biosynthesis of Aspergillus fumigatus. Int J Mol Sci. 2019;20(24):6192.
  27. Staats CC, Kmetzsch L, Schrank A, Vainstein MH. Fungal zinc metabolism and its connections to virulence. Front Cell Infect Microbiol. 2013;3:65.
  28. Kumar S, Acharya S, Jain S, Shukla S, Talwar D, Shah D, et al. Role of Zinc and Clinicopathological Factors for COVID-19-Associated Mucormycosis (CAM) in a Rural Hospital of Central India: A Case-Control Study. Cureus. 2022;14(2):e22528.
  29. Lulloff SJ, Hahn BL, Sohnle PG. Fungal susceptibility to zinc deprivation. J Lab Clin Med. 2004;144(4):208–14.
  30. Ding C, Festa RA, Sun T, Wang Z. Iron and copper as virulence modulators in human fungal pathogens. Mol Microbiol. 2014;93(1):10–23.
  31. Osherov N, May G. Conidial Germination in Aspergillus nidulans Requires RAS Signaling and Protein Synthesis. 2000;155(2):647–56.
  32. D’Enfert C, Bonini BM, Zapella PDA, Fontaine T, Da Silva AM, Terenzi HF. Neutral trehalases catalyse intracellular trehalose breakdown in the filamentous fungi Aspergillus nidulans and Neurospora crassa. Mol Microbiol. 1999;32(3):471–83.
  33. Trof RJ, Beishuizen A, Debets-Ossenkopp YJ, Girbes ARJ, Groeneveld ABJ. Management of invasive pulmonary aspergillosis in non-neutropenic critically ill patients. Intensive Care Med. 2007;33(10):1694–703.
  34. Stegenga ME, Van Der Crabben SN, Blümer RME, Levi M, Meijers JCM, Serlie MJ, et al. Hyperglycemia enhances coagulation and reduces neutrophil degranulation, whereas hyperinsulinemia inhibits fibrinolysis during human endotoxemia. Blood. 2008;112(1):82–9.
  35. Khanam A, Hithamani G, Naveen J, Pradeep SR, Barman S, Srinivasan K. Management of Invasive Infections in Diabetes Mellitus: A Comprehensive Review. Biologics. 2023;3(1):40–71.

 

 

Current Medical Mycology
Volume 10, Continuous
2024
Pages 1-11

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History

  • Receive Date: 20 June 2024
  • Revise Date: 12 October 2024
  • Accept Date: 02 November 2024
  • Publish Date: 22 November 2024

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