Acanthamoeba castellanii
(
A.
castellanii
) can cause
Acanthamoeba
keratitis,
a sight-threatening infection, as well as a fatal brain
infection termed granulomatous amoebic encephalitis, mostly in immunocompromised
individuals. In contrast,
Naegleria fowleri
(
N. fowleri
) causes a deadly infection involving the central
nervous system, recognized as primary amoebic encephalitis, mainly
in individuals partaking in recreational water activities or those
with nasal exposure to contaminated water. Worryingly, mortality rates
due to these infections are more than 90%, suggesting the need to
find alternative therapies. In this study, antiamoebic activity of
a peptide based on the structure of the antibiotic tyrocidine was
evaluated against
A. castellanii
and
N. fowleri
. The tyrocidine-derived peptide displayed significant amoebicidal
efficacy against
A. castellanii
and
N. fowleri
. At 250 μg/mL, the peptide drastically reduced amoebae viability
up to 13% and 21% after 2 h of incubation against
N. fowleri
and
A. castellanii.
, whereas, after 24 h of incubation,
the peptide showed 86% and 94% amoebicidal activity against
A. castellanii
and
N. fowleri
. Furthermore,
amoebae pretreated with 100 μg/mL peptide inhibited 35% and
53%
A. castellanii
and
N. fowleri
, while, at 250 μg/mL, 84% and 94%
A. castellanii
and
N. fowleri
failed to adhere to human cells.
Amoeba-mediated cell cytopathogenicity assays revealed 31% and 42%
inhibition at 100 μg/mL, while at 250 μg/mL 75% and 86%
A. castellanii
and
N. fowleri
were inhibited.
Assays revealed inhibition of encystation in both
A. castellanii
(58% and 93%) and
N. fowleri
(73% and 97%) at concentrations
of 100 and 250 μg/mL respectively. Importantly, tyrocidine-derived
peptide depicted minimal cytotoxicity to human cells and, thus, may
be a potential candidate in the rational development of a treatment
regimen against free-living amoebae infections. Future studies are
necessary to elucidate the in vivo effects of tyrocidine-derived peptide
against these and other pathogenic amoebae of importance.