Ultrastructural Study of Acanthamoeba polyphaga Trophozoites and Cysts Treated In Vitro with Cationic Carbosilane Dendrimers

Abstract

Cationic carbosilane dendrimers are branched molecules with antimicrobial properties. Their activity has been tested against Acanthamoeba polyphaga, a causative agent of Acanthamoeba keratitis, a severe ocular disease in humans. A. polyphaga trophozoites and cysts were exposed to different noncytotoxic cationic carbosilane dendrimers with proven antiamoebic activity. The effects of treatment on cell surface and cell ultrastructure were examined by scanning and transmission electron microscopy, respectively. Two of the dendrimers tested induced dramatic alterations of cellular ultrastructure in both trophozoites and cysts, including vacuolization, depletion of cytoplasmic contents, and reduced cell size. Additionally, we observed severe alterations of the plasma membrane with membrane blebbing in trophozoites and disruption in cysts. These alterations were also observed with chlorhexidine, a drug used for treatment of Acanthamoeba keratitis. Our results support that these compounds may target membranes, and their action is critical for parasite integrity.

Peganum harmala Extract Has Antiamoebic Activity to Acanthamoeba triangularis Trophozoites and Changes Expression of Autophagy-Related Genes

“…The loss of membrane integrity can lead to a leakage in the cytoplasmic content and cell death. This finding is in agreement with a previous study of Irene Heredero-Bermejo and her colleagues in 2020, describing how membrane alteration led to the Acanthamoeba cell death [ 51 ]. In addition, the presence of pores on the membrane after being exposed to the extract may indicate the amoebic cell death by necrosis [ 52 ].…”

Application of Dendrimers for Treating Parasitic Diseases

“…Amebic keratitis is generally treated with a combination of diamidine (hexamidine or propamidine isethionate) and biguanide (chlorhexidine or polyhexamethylene biguanide-PHMB) while no totally effective treatment for GAE has been found to date. Diamidine and biguanide alter the structure and permeability of the cell membrane, causing cell lysis [ 206 ]. These are well-tolerated drugs but prolonged therapy leads to ocular surface toxicity and the development of resistant strains [ 207 ].…”

“…This leads to an increase in cell permeability which can trigger the rupture of the membrane in such a way as to jeopardize the integrity of both trophozoites and cysts. All of these alterations can eventually lead to membrane rupture and cell death [ 206 ].…”

Dendrimers and Dendritic Materials: From Laboratory to Medical Practice in Infectious Diseases

“…Low generation cationic carbosilane dendrimers bearing ammonium or biguanide moieties have shown strong amoebicidal activity against trophozoites and cysts of Acanthamoeba spp., Figure 6 D (IC 50 = 2.4 mg/L; minimum cysticidal concentration MCC = 256 mg/L) [ 104 , 162 ]. Furthermore, they exhibit a synergistic effect with traditional drugs such as chlorhexidine, decreasing the required drug concentration 5–10 times using G1 dendrimers [ 163 ].…”

“…Figure reprinted from ref. [ 104 ]. ( E ) Evolution of PrP Sc levels in ScN2a cells after treatment with a G4 PPH dendrimer (10 µg/mL).…”