Skip to main content
SpringerLink
Log in

Tigecycline inhibits proliferation of Acanthamoeba castellanii

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

Acanthamoeba is an opportunistic protozoan parasite responsible for different diseases in humans, such as granulomatous amoebic encephalitis and amoebic keratitis. Tigecycline, a third-generation tetracycline antibiotic, has potential activity to treat most of the antibiotic resistant bacterial infections. The effects of tigecycline in eukaryotic cells as well as parasites are less well studied. In the present study, we tested the effects of tigecycline on trophozoites of Acanthamoeba castellanii. The inhibitory effect of tigecycline on Acanthamoeba was determined by resazurin reduction and trypan blue exclusion assays. We found that tigecycline significantly inhibited the growth of Acanthamoeba (46.4 % inhibition at the concentration of 100 μM) without affecting cell viability and induction of encystation, whereas other tetracycline groups of antibiotics such as tetracycline and doxycycline showed no inhibitory effects. Furthermore, tigecycline decreased cellular adenosine triphosphate (ATP) level by 26 % than the control and increased mitochondrial mass, suggesting mitochondrial dysfunction in tigecycline-treated cells. These findings suggest that mitochondrial dysfunction with decreased ATP production might play an important mechanism of tigecycline in suppression of Acanthamoeba proliferation.

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
Fig. 4

Similar content being viewed by others

References

  • Aichelburg AC et al (2008) Successful treatment of disseminated Acanthamoeba spp. infection with miltefosine. Emerg Infect Dis 14(11):1743–6

    Article  PubMed Central  PubMed  Google Scholar 

  • Aqeel Y, Siddiqui R, Iftikhar H, Khan NA (2013) The effect of different environmental conditions on the encystation of Acanthamoeba castellanii belonging to the T4 genotype. Exp Parasitol 135(1):30–5

    Article  PubMed  CAS  Google Scholar 

  • Baig AM, Iqbal J, Khan NA (2013) In vitro efficacies of clinically available drugs against growth and viability of an Acanthamoeba castellanii keratitis isolate belonging to the T4 genotype. Antimicrob Agents Chemother 57(8):3561–7

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Bang S, Edell E, Eghrari AO, Gottsch JD (2010) Treatment with voriconazole in 3 eyes with resistant Acanthamoeba keratitis. Am J Ophthalmol 149(1):66–9

    Article  PubMed  CAS  Google Scholar 

  • Bauer G, Berens C, Projan SJ, Hillen W (2004) Comparison of tetracycline and tigecycline binding to ribosomes mapped by dimethylsulphate and drug-directed Fe2+ cleavage of 16S rRNA. J Antimicrob Chemother 53(4):592–9

    Article  PubMed  CAS  Google Scholar 

  • Bouyer S, Imbert C, Daniault G, Cateau E, Rodier MH (2007) Effect of caspofungin on trophozoites and cysts of three species of Acanthamoeba. J Antimicrob Chemother 59(1):122–4

    Article  PubMed  CAS  Google Scholar 

  • Clarke B, Sinha A, Parmar DN, Sykakis E (2012) Advances in the diagnosis and treatment of Acanthamoeba keratitis. J Ophthalmol 2012:484892. doi:10.1155/2012/484892

    PubMed Central  PubMed  Google Scholar 

  • Fields RD, Lancaster MV (1993) Dual-attribute continuous monitoring of cell proliferation/cytotoxicity. Am Biotechnol Lab 11(4):48–50

    PubMed  CAS  Google Scholar 

  • Gerasimovskaya EV et al (2005) Extracellular ATP-induced proliferation of adventitial fibroblasts requires phosphoinositide 3-kinase, Akt, mammalian target of rapamycin, and p70 S6 kinase signaling pathways. J Biol Chem 280(3):1838–48

    Article  PubMed  CAS  Google Scholar 

  • Gonzalvez F et al (2013) Barth syndrome: cellular compensation of mitochondrial dysfunction and apoptosis inhibition due to changes in cardiolipin remodeling linked to tafazzin (TAZ) gene mutation. Biochim Biophys Acta 1832(8):1194–206

    Article  PubMed  CAS  Google Scholar 

  • Heredero-Bermejo I, Copa-Patino JL, Soliveri J, Gomez R, de la Mata FJ, Perez-Serrano J (2013) In vitro comparative assessment of different viability assays in Acanthamoeba castellanii and Acanthamoeba polyphaga trophozoites. Parasitol Res 112(12):4087–95

    Article  PubMed  CAS  Google Scholar 

  • Illingworth CD, Cook SD, Karabatsas CH, Easty DL (1995) Acanthamoeba keratitis: risk factors and outcome. Br J Ophthalmol 79(12):1078–82

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Khan NA (2006) Acanthamoeba: biology and increasing importance in human health. FEMS Microbiol Rev 30(4):564–95

    Article  PubMed  CAS  Google Scholar 

  • Kumar R, Lloyd D (2002) Recent advances in the treatment of Acanthamoeba keratitis. Clin Infect Dis 35(4):434–41

    Article  PubMed  Google Scholar 

  • Larson EM, Doughman DJ, Gregerson DS, Obritsch WF (1997) A new, simple, nonradioactive, nontoxic in vitro assay to monitor corneal endothelial cell viability. Invest Ophthalmol Vis Sci 38(10):1929–33

    PubMed  CAS  Google Scholar 

  • Leiter LM, Thatte HS, Okafor C, Marks PW, Golan DE, Bridges KR (1999) Chloramphenicol-induced mitochondrial dysfunction is associated with decreased transferrin receptor expression and ferritin synthesis in K562 cells and is unrelated to IRE-IRP interactions. J Cell Physiol 180(3):334–44

    Article  PubMed  CAS  Google Scholar 

  • Lorenzo-Morales J, Martin-Navarro CM, Lopez-Arencibia A, Arnalich-Montiel F, Pinero JE, Valladares B (2013) Acanthamoeba keratitis: an emerging disease gathering importance worldwide? Trends Parasitol 29(4):181–7

    Article  PubMed  Google Scholar 

  • Malatyali E, Tepe B, Degerli S, Berk S, Akpulat HA (2012) In vitro amoebicidal activity of four Peucedanum species on Acanthamoeba castellanii cysts and trophozoites. Parasitol Res 110(1):167–74

    Article  PubMed  Google Scholar 

  • Marciano-Cabral F, Cabral G (2003) Acanthamoeba spp. as agents of disease in humans. Clin Microbiol Rev 16(2):273–307

    Article  PubMed Central  PubMed  Google Scholar 

  • Marcussen M, Larsen PJ (1996) Cell cycle-dependent regulation of cellular ATP concentration, and depolymerization of the interphase microtubular network induced by elevated cellular ATP concentration in whole fibroblasts. Cell Motil Cytoskeleton 35(2):94–9

    Article  PubMed  CAS  Google Scholar 

  • Markowitz SM, Sobieski T, Martinez AJ, Duma RJ (1978) Experimental Acanthamoeba infections in mice pretreated with methylprednisolone or tetracycline. Am J Pathol 92(3):733–44

    PubMed Central  PubMed  CAS  Google Scholar 

  • Martin-Navarro CM et al (2014) PrestoBlue(R) and AlamarBlue(R) are equally useful as agents to determine the viability of Acanthamoeba trophozoites. Exp Parasitol. doi:10.1016/j.exppara.2014.03.024

    Google Scholar 

  • McBride J, Ingram PR, Henriquez FL, Roberts CW (2005) Development of colorimetric microtiter plate assay for assessment of antimicrobials against Acanthamoeba. J Clin Microbiol 43(2):629–34

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • McBride J, Mullen AB, Carter KC, Roberts CW (2007) Differential cytotoxicity of phospholipid analogues to pathogenic Acanthamoeba species and mammalian cells. J Antimicrob Chemother 60(3):521–5

    Article  PubMed  CAS  Google Scholar 

  • Moiseeva O, Bourdeau V, Roux A, Deschenes-Simard X, Ferbeyre G (2009) Mitochondrial dysfunction contributes to oncogene-induced senescence. Mol Cell Biol 29(16):4495–507

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Nakashima-Kamimura N et al (2005) MIDAS/GPP34, a nuclear gene product, regulates total mitochondrial mass in response to mitochondrial dysfunction. J Cell Sci 118(Pt 22):5357–67

    Article  PubMed  CAS  Google Scholar 

  • Olson MW, Ruzin A, Feyfant E, Rush TS 3rd, O’Connell J, Bradford PA (2006) Functional, biophysical, and structural bases for antibacterial activity of tigecycline. Antimicrob Agents Chemother 50(6):2156–66

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Perez-Rangel A et al (2013) Albendazole and its derivative JVG9 induce encystation on Giardia intestinalis trophozoites. Parasitol Res 112(9):3251–7

    Article  PubMed  Google Scholar 

  • Qvarnstrom Y, Nerad TA, Visvesvara GS (2013) Characterization of a new pathogenic Acanthamoeba Species, A. byersi n. sp., isolated from a human with fatal amoebic encephalitis. J Eukaryot Microbiol 60(6):626–33

    Article  PubMed  CAS  Google Scholar 

  • Rolon M, Vega C, Escario JA, Gomez-Barrio A (2006) Development of resazurin microtiter assay for drug sensibility testing of Trypanosoma cruzi epimastigotes. Parasitol Res 99(2):103–7

    Article  PubMed  Google Scholar 

  • Rose WE, Rybak MJ (2006) Tigecycline: first of a new class of antimicrobial agents. Pharmacotherapy 26(8):1099–110

    Article  PubMed  CAS  Google Scholar 

  • Sholl-Franco A, Fragel-Madeira L, Macama Ada C, Linden R, Ventura AL (2010) ATP controls cell cycle and induces proliferation in the mouse developing retina. Int J Dev Neurosci 28(1):63–73

    Article  PubMed  CAS  Google Scholar 

  • Siddiqui R, Khan NA (2012) Biology and pathogenesis of Acanthamoeba. Parasit Vectors 5:6. doi:10.1186/1756-3305-5-6

    Article  PubMed Central  PubMed  Google Scholar 

  • Skrtic M et al (2011) Inhibition of mitochondrial translation as a therapeutic strategy for human acute myeloid leukemia. Cancer Cell 20(5):674–88

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Slover CM, Rodvold KA, Danziger LH (2007) Tigecycline: a novel broad-spectrum antimicrobial. Ann Pharmacother 41(6):965–72

    Article  PubMed  CAS  Google Scholar 

  • Visvesvara GS, Moura H, Schuster FL (2007) Pathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea. FEMS Immunol Med Microbiol 50(1):1–26

    Article  PubMed  CAS  Google Scholar 

  • Walochnik J et al (2002) Cytotoxic activities of alkylphosphocholines against clinical isolates of Acanthamoeba spp. Antimicrob Agents Chemother 46(3):695–701

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Walochnik J et al (2009) Anti-Acanthamoeba efficacy and toxicity of miltefosine in an organotypic skin equivalent. J Antimicrob Chemother 64(3):539–45

    Article  PubMed  CAS  Google Scholar 

  • Waterhouse NJ, Goldstein JC, von Ahsen O, Schuler M, Newmeyer DD, Green DR (2001) Cytochrome c maintains mitochondrial transmembrane potential and ATP generation after outer mitochondrial membrane permeabilization during the apoptotic process. J Cell Biol 153(2):319–28

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Webster D et al (2012) Treatment of granulomatous amoebic encephalitis with voriconazole and miltefosine in an immunocompetent soldier. Am J Trop Med Hyg 87(4):715–8

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Microbiology, Keimyung University School of Medicine, 1095 Dalgubeol-daero, Dalseo-gu, Daegu, 704-701, Republic of Korea

    Bijay Kumar Jha, Incheol Seo, Seong-Il Suh, Min-Ho Suh & Won-Ki Baek

  2. Department of Parasitology, Dong-A University College of Medicine, Busan, 602-714, Republic of Korea

    Hyun-Hee Kong

Authors
  1. Bijay Kumar Jha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Incheol Seo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hyun-Hee Kong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seong-Il Suh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Min-Ho Suh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Won-Ki Baek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Won-Ki Baek.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jha, B.K., Seo, I., Kong, HH. et al. Tigecycline inhibits proliferation of Acanthamoeba castellanii . Parasitol Res 114, 1189–1195 (2015). https://doi.org/10.1007/s00436-014-4302-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-014-4302-1

Keywords

Search

Navigation