Multiple genetic loci define Ca++ utilization by bloodstream malaria parasites.

Abstract:

BACKGROUND:Bloodstream malaria parasites require Ca++ for their development, but the sites and mechanisms of Ca++ utilization are not well understood. We hypothesized that there may be differences in Ca++ uptake or utilization by genetically distinct lines of P. falciparum. These differences, if identified, may provide insights into molecular mechanisms. RESULTS:Dose response studies with the Ca++ chelator EGTA (ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid) revealed stable differences in Ca++ requirement for six geographically divergent parasite lines used in previous genetic crosses, with the largest difference seen between the parents of the HB3 x Dd2 cross. Genetic mapping of Ca++ requirement yielded complex inheritance in 34 progeny clones with a single significant locus on chromosome 7 and possible contributions from other loci. Although encoded by a gene in the significant locus and a proposed Ca++ target, PfCRT (P. falciparum chloroquine resistance transporter), the primary determinant of clinical resistance to the antimalarial drug chloroquine, does not appear to contribute to this quantitative trait. Stage-specific application of extracellular EGTA also excluded determinants associated with merozoite egress and erythrocyte reinvasion. CONCLUSIONS:We have identified differences in Ca++ utilization amongst P. falciparum lines. These differences are under genetic regulation, segregating as a complex trait in genetic cross progeny. Ca++ uptake and utilization throughout the bloodstream asexual cycle of malaria parasites represents an unexplored target for therapeutic intervention.

journal_name

BMC Genomics

journal_title

BMC genomics

authors

Apolis L,Olivas J,Srinivasan P,Kushwaha AK,Desai SA

doi

10.1186/s12864-018-5418-y

subject

Has Abstract

pub_date

2019-01-16 00:00:00

pages

47

issue

1

issn

1471-2164

pii

10.1186/s12864-018-5418-y

journal_volume

20

pub_type

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