Evaluation of Acanthamoeba myosin-IC as a potential therapeutic target.
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.
University Institute of Tropical Diseases and Public Health of the Canary Islands, University of La Laguna, Canary Islands, Spain.
Carmen M
CM
Martín-Navarro
Jacob
J
Lorenzo-Morales
Atteneri
A
López-Arencibia
María
M
Reyes-Batlle
José E
JE
Piñero
Basilio
B
Valladares
Sutherland K
SK
Maciver
D000048:Acanthamoeba / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D020868:Gene Silencing; D006801:Humans; D009218:Myosins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics
D000890:Anti-Infective Agents; D034741:RNA, Small Interfering; D009218:Myosins