dictyNews
Electronic Edition
Volume 50, number 6
May 17, 2024
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Abstracts
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A longer-chain acylated derivative of Dictyostelium
differentiation-inducing factor-1 enhances the antimalarial
activity against Plasmodium parasites.
Naoko Yoshida 1, Haruhisa Kikuchi 2, Makoto Hirai 1, Betty
Balikagala 1, Denis A. Anywar 3, Hikari Taka 4, Naoko Kaga
4, Yoshiki Miura 4, Naoyuki Fukuda 1, Emmanuel I. Odongo-Aginya
3, Yuzuru Kubohara 5, Toshihiro Mita
1 Department of Tropical Medicine and Parasitology, Faculty of
Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku,
Tokyo 113-8421, Japan
2 Division of Natural Medicines, Faculty of Pharmacy, Keio
University, Tokyo 105-8512, Japan
3 Faculty of Medicine, Gulu University, P.O. Box 166, Gulu, Uganda
4 Laboratory of Proteomics and Biomolecular Science, Biomedical
Research Core Facilities, Faculty of Medicine, Juntendo University,
2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
5 Laboratory of Health and Life Science, Graduate School of Health
and Sports Science, Juntendo University, Inzai, Chiba 270-1695,
Japan
Biochemical Pharmacology, In press.
The spread of malarial parasites resistant to first-line treatments
such as artemisinin combination therapies is a global health
concern. Differentiation-inducing factor 1 (DIF-1) is a chlorinated
alkylphenone (1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)
hexan-1-one) originally found in the cellular slime mould
Dictyostelium discoideum. We previously showed that some
derivatives of DIF-1, particularly DIF-1(+2)
(1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl) octan-1-one),
exert potent antimalarial activities. In this study, we synthesised
DIF-1(+3) (1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)
nonan-1-one). We then evaluated the effects of DIF-1(+3) in vitro
on Plasmodium falciparum and in vivo over 7 days (50–100 mg/kg/day)
in a mouse model of Plasmodium berghei. DIF-1(+3) exhibited a
half-maximal inhibitory concentration of approximately 20–30% of
DIF-1(+2) in three laboratory strains with a selectivity
index > 263, including in strains resistant to chloroquine and
artemisinin. Parasite growth and multiplication were almost
completely suppressed by treatment with 100 mg/kg DIF-1(+3). The
survival time of infected mice was significantly increased
(P = 0.006) with no apparent adverse effects. In summary, addition
of an acyl group to DIF-1(+2) to prepare DIF-1(+3) substantially
enhanced antimalarial activity, even in drug-resistant malaria,
indicating the potential of applying DIF-1(+3) for malaria treatment.
Submitted by Yuzuru Kubohara [[log in to unmask]]
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The greenbeard gene tgrB1 regulates altruism and cheating in
Dictyostelium discoideum
Mariko Katoh-Kurasawa, Peter Lehmann, and Gad Shaulsky
Department of Molecular and Human Genetics, Baylor College of
Medicine, Houston, TX 77030
Nature Communications https://rdcu.be/dHDus
Greenbeard genetic elements encode rare perceptible signals, signal
recognition ability, and altruism towards others that display the
same signal. Putative greenbeards have been described in various
organisms but direct evidence for all the properties in one system
is scarce. The tgrB1-tgrC1 allorecognition system of Dictyostelium
discoideum encodes two polymorphic membrane proteins which protect
cells from chimerism-associated perils.During development, TgrC1
functions as a ligand-signal and TgrB1 as its receptor, but evidence
for altruism has been indirect. Here, we show that mixing wild-type
and activated tgrB1 cells increases wild-type spore production and
relegates the mutants to the altruistic stalk, whereas mixing
wild-type and tgrB1-null cells increases mutant spore production
and wild-type stalk production. The tgrB1-null cells cheat only
on partners that carry the same tgrC1-allotype. Therefore, TgrB1
activation confers altruism whereas TgrB1 inactivation causes
allotype-specific cheating, supporting the greenbeard concept and
providing insight into the relationship between allorecognition,
altruism, and exploitation.
Submitted by Gad Shaulsky
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