Evaluation of Acanthamoeba Myosin-IC as a Potential Therapeutic Target

Carmen M. Martin-Navarro*, Jacob Lorenzo-Morales, Atteneri Lopez-Arencibia, Maria Reyes-Batlle, Jose E. Pinero, Basilio Valladares, Sutherland K. Maciver

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Members of the genus Acanthamoeba are facultative pathogens of humans, causing a sight-threatening keratitis and a fatal encephalitis. We have targeted myosin-IC by using small interfering RNA (siRNA) silencing as a therapeutic approach, since it is known that the function of this protein is vital for the amoeba. In this work, specific siRNAs against the Acanthamoeba myosin-IC gene were developed. Treated and control amoebae were cultured in growth and encystment media to evaluate the induced effects after myosin-IC gene knockdown, as we have anticipated that cyst formation may be impaired. The effects of myosin-IC gene silencing were inhibition of cyst formation, inhibition of completion of cytokinesis, inhibition of osmoregulation under osmotic stress conditions, and death of the amoebae. The finding that myosin-IC silencing caused incompletion of cytokinesis is in agreement with earlier suggestions that the protein plays a role in cell locomotion, which is necessary to pull daughter cells apart after mitosis in a process known as "traction-mediated cytokinesis". We conclude that myosin-IC is a very promising potential drug target for the development of much-needed antiamoebal drugs and that it should be further exploited for Acanthamoeba therapy.

Original languageEnglish
Pages (from-to)2150-2155
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume58
Issue number4
DOIs
Publication statusPublished - Apr 2014

Keywords

  • RNA INTERFERENCE
  • CASTELLANII
  • LOCALIZATION
  • INHIBITION
  • STRAINS
  • ENZYME

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