dictyNews
Electronic Edition
Volume 46, number 6
February 28, 2020
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Abstracts
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13 Plus 1: A 30-Year Perspective on Microtubule-Based Motility
in Dictyostelium
Michael P. Koonce
Wadsworth Center – Albany NY
Cells, in press
Individual gene analyses of microtubule-based motor proteins
in Dictyostelium discoideum have provided a rough draft of its
machinery for cytoplasmic organization and division. This review
collates their activities and looks forward to what is next. A
comprehensive approach that considers the collective actions of
motors, how they balance rates and directions, and how they
integrate with the actin cytoskeleton will be necessary for a
complete understanding of cellular dynamics.
submitted by: Michael Koonce [[log in to unmask]]
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Talin B regulates collective cell migration via PI3K signaling in
Dictyostelium discoideum mounds
Shin-ichi Yamazaki, Hidenori Hashimura, Yusuke V. Morimoto,
Yukihiro Miyanaga, Satomi Matsuokad, Yoichiro Kamimura, and
Masahiro Ueda
Biochemical and Biophysical Research Communications
available online https://doi.org/10.1016/j.bbrc.2020.02.060
Collective cell migration is a key process during the development of
multicellular organisms, in which the migrations of individual cells are
coordinated through chemical guidance and physical contact between
cells. Talin has been implicated in mechanical linkage between actin-
based motile machinery and adhesion molecules, but how talin
contributes to collective cell migration is unclear. Here we show that
talin B is involved in chemical coordination between cells for collective
cell migration at the multicellular mound stage in the development of
Dictyostelium discoideum. From early aggregation to the mound
formation, talB-null cells exhibited collective migration normally with
cAMP relay. Subsequently, talB-null cells showed developmental arrest
at the mound stage, and at the same time, they had impaired collective
migration and cAMP relay, while wild-type cells exhibited rotational cell
migration continuously in concert with cAMP relay during the mound
stage. Genetic suppression of PI3K activity partially restored talB-null
phenotypes in collective cell migration and cAMP relay. Overall, our
observations suggest that talin B regulates chemical coordination via
PI3K-mediated signaling in a stage-specific manner for the
multicellular development of Dictyostelium cells.
submitted by: Yoichiro Kamimura [[log in to unmask]]
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Identification of Anti-Mycobacterium and Anti-Legionella Compounds
With Potential Distinctive Structural Scaffolds From an HD-PBL Using
Phenotypic Screens in Amoebae Host Models
Nabil Hanna1*†, Sébastien Kicka1†, Gianpaolo Chiriano2, Christopher
Harrison3, Hajer Ouertatani Sakouhi4, Valentin Trofimov1, Agata Kranjc2,
Jahn Nitschke1, Marco Pagni5, Pierre Cosson4, Hubert Hilbi6,
Leonardo Scapozza2 and Thierry Soldati1*
1 Department of Biochemistry, Faculty of Sciences, University of Geneva,
Geneva, Switzerland,
2 Pharmaceutical Biochemistry/Chemistry, School of Pharmaceutical
Sciences, University of Geneva, Geneva, Switzerland,
3 Max von Pettenkofer Institute, Ludwig Maximilian University of Munich,
Munich, Germany,
4 Department of Cell Physiology and Metabolism, Faculty of Medicine,
University of Geneva, Geneva, Switzerland,
5 Swiss Institute of Bioinformatics, Lausanne, Switzerland,
6 Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland
Frontiers in Microbiology, Antimicrobials, Resistance and Chemotherapy
https://www.frontiersin.org/articles/10.3389/fmicb.2020.00266/full
Tubercular Mycobacteria and Legionella pneumophila are the causative
agents of potentially fatal respiratory diseases due to their intrinsic
pathogenesis but also due to the emergence of antibiotic resistance
that limits treatment options. The aim of our study was to explore the
antimicrobial activity of a small ligand-based chemical library of 1,255
structurally diverse compounds. These compounds were screened in a
combination of three assays, two monitoring the intracellular growth of
the pathogenic bacteria, Mycobacterium marinum and L. pneumophila,
and one assessing virulence of M. marinum. We set up these assays
using two amoeba strains, the genetically tractable social amoeba
Dictyostelium discoideum and the free-living amoeba Acanthamoeba
castellanii. In summary, sixty-four (5.1%) compounds showed
anti-infective/anti-virulence activity in at least one of the 3 assays. The
intracellular assays hit rate varied between 1.7% (n=22) for M. marinum
and 2.8% (n=35) for L pneumophila with 7 compounds in common for
both pathogens. In parallel, 1.2 % (n= 15) of the tested compounds
were able to restore D. discoideum growth in the presence of
M. marinum spiked in a lawn of food bacteria. We also validated the
generality of the hits identified in the A. castellanii-M. marinum anti-
infective screen using the D. discoideum-M. marinum host-pathogen
model. The characterization of anti-infective and antibacterial hits in the
latter infection model revealed compounds able to reduce intracellular
growth more than 50% at 30 μM. Moreover, the chemical space and
physico-chemical properties of the anti-M. marinum hits were compared
to standard and candidate M. tuberculosis drugs using ChemGPS-NP. A
principle component analysis identified separate clusters for anti-M.
marinum and anti-L. pneumophila hits unveiling the potentially new
physico-chemical properties of these hits compared to standard and
candidate M. tuberculosis drugs. Our studies underscore the relevance
of using a combination of low-cost and low-complexity assays with full
3R compliance in concert with a rationalized focused library of compounds
to identify new chemical scaffolds and to dissect some of their properties
prior to taking further steps towards compound development.
submitted by: Thierry Soldati [[log in to unmask]]
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