Dissection of the hierarchy and synergism of the bile derived signal on Cryptosporidium parvum excystation and infectivity.

Abstract:

:Bile salts have been identified as an important trigger for excystation of Cryptosporidium oocysts but the hierarchy or synergism of this signal in relation to other triggers involved in excystation is poorly understood. In addition to excystation, bile salts have also been reported to increase the invasiveness of sporozoites within in vitro culture, possibly by affecting the secretory pathway via modification of intracellular calcium signalling. Nevertheless, incorporation of bile or bile salts into in vitro assays is not universal, with recent reports of negative effects on parasite growth. Here we report that bile and sodium taurocholate significantly affect both excystation rate and parasite in vitro growth. We demonstrate that their effect on excystation is dose, time and pre-treatment temperature dependent, while increases in parasite replication appear to be associated with modulation of parasite intracellular calcium and increased host cell susceptibility to infection. Notably, we illustrate that bile has a significant effect on host cells and can be cytotoxic at concentrations not much higher than those currently used for in vitro assays. This work should assist with more rational design of in vitro culture systems, with significant considerations for assay format when incorporating bile or bile salts as an excystation trigger.

journal_name

Parasitology

journal_title

Parasitology

authors

King BJ,Keegan AR,Phillips R,Fanok S,Monis PT

doi

10.1017/S0031182012000984

subject

Has Abstract

pub_date

2012-10-01 00:00:00

pages

1533-46

issue

12

eissn

0031-1820

issn

1469-8161

pii

S0031182012000984

journal_volume

139

pub_type

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