TY - JOUR
T1 - Effects of dextran sulfates on the acute infection and growth stages of Toxoplasma gondii
AU - Ishiwa, Akiko
AU - Kobayashi, Kyousuke
AU - Takemae, Hitoshi
AU - Sugi, Tatsuki
AU - Gong, Haiyan
AU - Recuenco, Frances C.
AU - Murakoshi, Fumi
AU - Inomata, Atsuko
AU - Horimoto, Taisuke
AU - Kato, Kentaro
N1 - Funding Information:
Acknowledgments This study was supported by grant-in-aids for Young Scientists, Exploratory Research, Scientific Research on Innovative Areas (3308) from the Ministry of Education, Culture, Science, Sports, and Technology (MEXT) of Japan; Bio-oriented Technology Research Advancement Institution (BRAIN); and Program to Disseminate Tenure Tracking System from Japan Science and Technology Agency (JST).
PY - 2013/12
Y1 - 2013/12
N2 - Toxoplasma gondii is one of the most prevalent parasites, causing toxoplasmosis in various warm-blooded animals, including humans. Because of the broad range of hosts susceptible to T. gondii, it had been postulated that a universal component of the host cell surface, such as glycosaminoglycans (GAGs), may act as a receptor for T. gondii infection. Carruthers et al. (Infect Immun 68:4005-4011, 2000) showed that soluble GAGs have also been shown to disrupt parasite binding to human fibroblasts. Therefore, we investigated the inhibitory effect of GAGs and their analogue dextran sulfate (DS) on T. gondii infection. For up to 24 h of incubation after inoculation of T. gondii, the inhibitory effect of GAGs on T. gondii infection and growth inside the host cell was weak. In contrast, DS markedly inhibited T. gondii infection. Moreover, low molecular weight DS particularly slowed the growth of T. gondii inside host cells. DS10 (dextran sulfate MW 10 kDa) was the most effective agent in these in vitro experiments and was therefore tested for its inhibitory effects in animal experiments; infection inhibition by DS10 was confirmed under these in vivo conditions. In this report, we showed that DSs, especially DS10, have the potential of a new type of drug for toxoplasmosis.
AB - Toxoplasma gondii is one of the most prevalent parasites, causing toxoplasmosis in various warm-blooded animals, including humans. Because of the broad range of hosts susceptible to T. gondii, it had been postulated that a universal component of the host cell surface, such as glycosaminoglycans (GAGs), may act as a receptor for T. gondii infection. Carruthers et al. (Infect Immun 68:4005-4011, 2000) showed that soluble GAGs have also been shown to disrupt parasite binding to human fibroblasts. Therefore, we investigated the inhibitory effect of GAGs and their analogue dextran sulfate (DS) on T. gondii infection. For up to 24 h of incubation after inoculation of T. gondii, the inhibitory effect of GAGs on T. gondii infection and growth inside the host cell was weak. In contrast, DS markedly inhibited T. gondii infection. Moreover, low molecular weight DS particularly slowed the growth of T. gondii inside host cells. DS10 (dextran sulfate MW 10 kDa) was the most effective agent in these in vitro experiments and was therefore tested for its inhibitory effects in animal experiments; infection inhibition by DS10 was confirmed under these in vivo conditions. In this report, we showed that DSs, especially DS10, have the potential of a new type of drug for toxoplasmosis.
UR - http://www.scopus.com/inward/record.url?scp=84890191582&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84890191582&partnerID=8YFLogxK
U2 - 10.1007/s00436-013-3608-8
DO - 10.1007/s00436-013-3608-8
M3 - Article
C2 - 24096605
AN - SCOPUS:84890191582
SN - 0932-0113
VL - 112
SP - 4169
EP - 4176
JO - Parasitology Research
JF - Parasitology Research
IS - 12
ER -