Abstract
Larvae of the insect Galleria mellonella were employed to assess the in vivo antifungal efficacy of ([Ag2(mal)(phen)3]), AgNO3 and 1,10-phenanthroline. Larvae pre-inoculated with these compounds were protected from a subsequent lethal infection by the yeast Candida albicans while larvae inoculated 1 and 4 h post-infection showed significantly increased survival (P < 0.01) compared to control larvae. Administration of these compounds resulted in an increase over 48 h in the density of insect haemocytes (immune cells) but there was no widespread activation of genes for antimicrobial peptides. This work demonstrates that G. mellonella larvae may be employed to ascertain the antifungal efficacy of silver(I) compounds and offers a rapid and effective means of assessing the in vivo activity of inorganic antimicrobial compounds.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- AMP:
-
Antimicrobial peptide(s)
- apim:
-
1-(3-Aminopropyl) imidazole
- malH2 :
-
Malonic acid
- phen:
-
1,10-Phenanthroline
References
Adams AP, Santschi EM, Mellencamp MA (1999) Antibacterial properties of a silver chloride-coated nylon wound dressing. Vet Surg 28(4):219–225
Ascioglu S et al (2002) Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopietic stem cell transplants: an international consensus. Clin Infect Dis 34(1):7–14. doi:10.1086/323335
Benjamin DK Jr, Garges H, Steinbach WJ (2004) Candida bloodstream infection in neonates. Semin Perinatol 27(5):375–383. doi:10.1016/S0146-0005(03)00061-2
Bergin D, Brennan M, Kavanagh K (2003) Fluctuations in haemocyte density and microbial load may be used as indicators of fungal pathogenicity in larvae of Galleria mellonella. Microbes Infect 5(15):1389–1395. doi:10.1016/j.micinf.2003.09.019
Bergin D, Murphy L, Keenan J, Clynes M, Kavanagh K (2006) Pre-exposure to yeast protects larvae of Galleria mellonella from subsequent lethal infection by Candida albicans and is mediated by the increased expression of antimicrobial peptides. Microbes Infect 8(8):2105–2112. doi:10.1016/j.micinf.2006.03.005
Bernall A, Kimbrell DA (2000) Drosophila Thor participates in host immune defense and connects a translational regulator with innate immunity. Proc Natl Acad Sci USA 97(11):6019–6024. doi:10.1073/pnas.100391597
Brennan M, Thomas DY, Whiteway M, Kavanagh K (2002) Correlation between virulence of Candida albicans mutants in mice and Galleria mellonella larvae. FEMS Immunol Med Microbiol 34(2):153–157. doi:10.1111/j.1574-695X.2002.tb00617.x
Cotter G, Doyle S, Kavanagh K (2000) Development of an insect model for the in vivo pathogenicity testing of yeasts. FEMS Immunol Med Microbiol 27:163–169. doi:10.1111/j.1574-695X.2000.tb01427.x
Coyle B, Kavanagh K, McCann M, Deveraux M, Geraghty M (2003) Mode of anti-fungal activity of 1,10-phenanthroline and its Cu(II), Mn(II) and Ag(I) complexes. Biometals 16(2):321–329. doi:10.1023/A:1020695923788
Coyle B, McCann M, Kavanagh K, Devereux M, McKee V, Kayal N, Egan D, Deegan C, Finn GF (2004) X-ray crystal structure, anti-fungal and anti-cancer activity of [Ag2(NH3)2(salH)2] (salH2 = salicylic acid). J Inorg Biochem 98(8):1361–1366. doi:10.1016/j.jinorgbio.2004.04.016
Desai MH, Herndon DN (1988) Eradication of Candida burn wound septicemia in massively burned patients. J Trauma 28(2):140–145. doi:10.1097/00005373-198802000-00002
Fidel PL (2006) Candida-host interactions in HIV disease: relationship in oropharyngeal candidiasis. Adv Dent Res 19(1):80–84
Hamamoto H, Kurokawa K, Kaito C, Kamura K, Manitra Razanajatovo I, Kusuhara H, Santa T, Sekimizu K (2004) Quantitative evaluation of the therapeutic effects of antibiotics using silkworms infected with human pathogenic microorganisms. Antimicrob Agents Chemother 48:774–779. doi:10.1128/AAC.48.3.774-779.2004
Holder IA, Durkee P, Supp AP, Boyce ST (2003) Assessment of a silver-coated barrier dressing for potential use with skin grafts on excised burns. Burns 29:445–448. doi:10.1016/S0305-4179(03)00046-9
Kaufman D (2003) Fungal infection in the very low birthweight infant. Curr Opin Infect Dis 17(3):253–259. doi:10.1097/00001432-200406000-00014
Kavanagh K, Reeves EP (2004) Exploiting the potential of Insects for in vivo pathogenicity testing of microbial pathogens. FEMS Microbiol Rev 28:101–112. doi:10.1016/j.femsre.2003.09.002
Khare MD, Bukhari SS, Swann A, Spiers P, McLaren I, Myers J (2007) Reduction of catheter-related colonization by the use of a silver zoelite-impregnated central vascular catheter in adult critical care. J Infect 54:146–150. doi:10.1016/j.jinf.2006.03.002
Lionakis MS, Kontoyiannis DP (2005) Fruit flies as a minihost model for studying drug activity and virulence in Aspergillus. Med Mycol 43(Supplement):111–114. doi:10.1080/13693780400020030
Mahajan-Miklos S, Tan MW, Rahme LG, Ausubel FM (1999) Molecular mechanism of bacterial virulence elucidated using a Pseudomonas aeruginosa–Caenorhabitis elegans pathogenesis model. Cell 96:47–56. doi:10.1016/S0092-8674(00)80958-7
McCann M, Geraghty M, Devereux M, O Shea D, Mason J, O Sullivan L (2000) Insights into the mode of action of the anti-Candida activity of 1,10-phenanthroline and its metal chelates. Met Based Drugs 7(4):185–193. doi:10.1155/MBD.2000.185
McCann M, Coyle B, McKay S, McCormack P, Kavanagh K, Devereux M, McKee V, Kinsella P, O Connor R, Clynes M (2004) Synthesis and X-ray crystal structure of [Ag(phendio)2]ClO4 (phendio = 1,10-phenanthroline-5,6-dione) and its effects on fungal and mammalian cells. Biometals 17(6):635–645. doi:10.1007/s10534-004-1229-5
Morell M, Fraser VJ, Kollef MH (2005) Delaying the empiric treatment of Candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob Agents Chemother 49:3640–3645. doi:10.1128/AAC.49.9.3640-3645.2005
Mylonakis E, Moreno R, El Khoury JB, Idnurm A, Heitman J, Calderwood SB, Ausubel FM, Diener A (2005) Galleria mellonella as a model system to study Cryptococcus neoformons pathogenesis. Infect Immun 73(7):3842–3850. doi:10.1128/IAI.73.7.3842-3850.2005
Ratcliffe N (1985) Invertebrate immunity—a primer for the non specialist. Immunol Lett 10(5):253–270. doi:10.1016/0165-2478(85)90100-2
Rho D, Karandikar B, Bonn-Savage N, Gibbins B, Roullet JB (2008) Antimicrobial surface functionalization of plastic catheters by silver nanoparticles. J Antimicrob Chemother 61:869–876. doi:10.1093/jac/dkn034
Rowan R, Tallon T, Sheahan AM, Curran R, McCann M, Kavanagh K, Deveraux M, McKee V (2006) Silver bullets in antimicrobial chemotherapy: synthesis, characterisation and biological screening of some new Ag(I)-containing imidazole complexes. Polyhedron 28(5):1771–1778. doi:10.1016/j.poly.2005.11.021
Thomas S, McCubbin P (2003) A comparison of the antimicrobial effects of four silver-containing dressings on three organisms. J Wound Care 12:101–107
Totaro P, Rambaldini M (2008) Efficacy of antimicrobial activity of slow release silver nanoparticles dressing in post-cardiac surgery mediastinitis. Interact Cardiovasc Thorac Surg. doi:10.1510/icvts.2008.188870
Wright JB, Lam K, Hansen B, Burrell E (1999) Efficacy of topical silver against fungal burn wound pathogens. Am J Infect Control 27(4):344–350. doi:10.1016/S0196-6553(99)70055-6
Acknowledgments
This work was supported by funding from the Higher Education Authority of Ireland through the Programme for Research in Third Level Institutes 3 (2002–2007).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Rowan, R., Moran, C., McCann, M. et al. Use of Galleria mellonella larvae to evaluate the in vivo anti-fungal activity of [Ag2(mal)(phen)3]. Biometals 22, 461–467 (2009). https://doi.org/10.1007/s10534-008-9182-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10534-008-9182-3