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  1. Fulltext Novel insights into the potential role of ion transport in sensory perception in Acanthamoeba
    Siddiqui R, Roberts SK, Ong TYY, Mungroo MR, Anwar A, Khan NA
    Parasit Vectors, 2019 Nov 14;12(1):538.
    PMID: 31727139 DOI: 10.1186/s13071-019-3785-0
    BACKGROUND: Acanthamoeba is well known to produce a blinding keratitis and serious brain infection known as encephalitis. Effective treatment is problematic, and can continue up to a year, and even then, recurrence can ensue. Partly, this is due to the capability of vegetative amoebae to convert into resistant cysts. Cysts can persist in an inactive form for decades while retaining their pathogenicity. It is not clear how Acanthamoeba cysts monitor environmental changes, and determine favourable conditions leading to their emergence as viable trophozoites.

    METHODS: The role of ion transporters in the encystation and excystation of Acanthamoeba remains unclear. Here, we investigated the role of sodium, potassium and calcium ion transporters as well as proton pump inhibitors on A. castellanii encystation and excystation and their effects on trophozoites.

    RESULTS: Remarkably 3',4'-dichlorobenzamil hydrochloride a sodium-calcium exchange inhibitor, completely abolished excystation of Acanthamoeba. Furthermore, lanthanum oxide and stevioside hydrate, both potassium transport inhibitors, resulted in the partial inhibition of Acanthamoeba excystation. Conversely, none of the ion transport inhibitors affected encystation or had any effects on Acanthamoeba trophozoites viability.

    CONCLUSIONS: The present study indicates that ion transporters are involved in sensory perception of A. castellanii suggesting their value as potential therapeutic targets to block cellular differentiation that presents a significant challenge in the successful prognosis of Acanthamoeba infections.

    Matched MeSH terms: Acanthamoeba/metabolism*
  2. Fulltext The Development of Drugs against Acanthamoeba Infections
    Siddiqui R, Aqeel Y, Khan NA
    Antimicrob Agents Chemother, 2016 11;60(11):6441-6450.
    PMID: 27600042 DOI: 10.1128/AAC.00686-16
    For the past several decades, there has been little improvement in the morbidity and mortality associated with Acanthamoeba keratitis and Acanthamoeba encephalitis, respectively. The discovery of a plethora of antiacanthamoebic compounds has not yielded effective marketed chemotherapeutics. The rate of development of novel antiacanthamoebic chemotherapies of translational value and the lack of interest of the pharmaceutical industry in developing such chemotherapies have been disappointing. On the other hand, the market for contact lenses/contact lens disinfectants is a multi-billion-dollar industry and has been successful and profitable. A better understanding of drugs, their targets, and mechanisms of action will facilitate the development of more-effective chemotherapies. Here, we review the progress toward phenotypic drug discovery, emphasizing the shortcomings of useable therapies.
    Matched MeSH terms: Acanthamoeba/metabolism
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