In Vitro Efficacy of Corifungin against Acanthamoeba castellanii Trophozoites and Cysts

Abstract

cPainful blinding keratitis and fatal granulomatous amebic encephalitis are caused by the free-living amebae Acanthamoeba spp. Several prescription eye medications are used to treat Acanthamoeba keratitis, but the infection can be difficult to control because of recurrence of infection. For the treatment of encephalitis, no single drug was found useful, and in spite of the use of a combination of multiple drugs, the mortality rate remains high. Therefore, efficient, novel drugs are urgently needed for the treatment of amebic keratitis and granulomatous amebic encephalitis. In this study, we identified corifungin, a water-soluble polyene macrolide, as amebicidal. In vitro, it was effective against both the trophozoites and the cysts. Transmission electron microscopy of Acanthamoeba castellanii incubated with corifungin showed the presence of swollen mitochondria, electrondense granules, degeneration of cytoplasm architecture, and loss of nuclear chromatin structure. These changes were followed by lysis of amebae. Corifungin also induced the encystment process of A. castellanii. There were alterations in the cyst cell wall followed by lysis of the cysts. Corifungin is a promising therapeutic option for keratitis and granulomatous amebic encephalitis. Free-living Acanthamoeba spp. cause keratitis, a serious eye infection that can occur in healthy individuals wearing contact lenses, as well as chronic granulomatous amebic encephalitis (GAE) leading to death in immunocompromised persons. Acanthamoeba has a worldwide distribution and is the most common ameba found in the environment. Coincident with the number of Acanthamoeba keratitis cases in the United States has been an increase in developing countries. Wearing of contact lenses is now recognized as the leading risk factor for keratitis (1-3). In the United States, the estimated number of keratitis cases is 1.36 per million contact lens wearers (4, 5). GAE is a relatively rare disease. Approximately 150 cases have been reported worldwide (5). GAE results from inhalation of amebae through the nasal cavities and lungs, or introduction through skin lesions followed by access to the central nervous system by hematogenous spread or through the olfactory neuroepithelium (6). Clinical manifestations include headache, fever, nausea, vomiting, behavioral changes, stiff neck, lethargy, increased intracranial pressure, and, in the later stage, loss of consciousness, seizures, coma, and death (7-9).The drugs recommended for the treatment of Acanthamoeba keratitis include polyhexamethylene biguanide (0.02%) or chlorhexidine (0.02%) along with a diamidine (either 0.1% propamidine or 0.1% hexamidine) (10). Corticosteroids are applied topically to control corneal inflammation, pain, and scleritis, particularly following keratoplasty (11). While this antimicrobial treatment can kill the trophozoites, the resistance of Acanthamoeba cysts to antimicrobials can lead to the recurrence of keratitis. For GAE, combination therapies were found more successful than single-drug therapies, a...

Identification of anisomycin, prodigiosin and obatoclax as compounds with broad-spectrum anti-parasitic activity

“…Giardia lamblia strain WB was grown and maintained at 37˚C in TYI media. Acanthamoeba castellanii strain Ma trophozoites (T4 genotype) were cultured at 28˚C in PYG medium according to a modified technique [69].…”

Yersinia pestis Resists Predation by Acanthamoeba castellanii and Exhibits Prolonged Intracellular Survival

“…tissue culture plate. The viability of A. castellanii trophozoites was confirmed using trypan blue exclusion staining (57). For coculture studies of bacteria with amoebae, approximately 2.5 ϫ 10 5 viable trophozoites/ml were seeded per well of the tissue culture plate and allowed to adhere to the well overnight at 25°C.…”

Isolation of <em>Naegleria spp.</em> from a Brazilian Water Source

“…PAM is a fatal infection caused by Naegleria fowleri whose amoeboflagellate can reach the central nervous system (CNS) through the olfactory neuroepithelial pathway [22]. Seven to fourteen days after the appearance of symptoms 95% of the cases reported to date lead to death [18,[24][25][26].…”