dictyNews
Electronic Edition
Volume 47, number 5
February 19, 2021
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Abstracts
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How Phagocytic Cells Kill Different Bacteria: a Quantitative
Analysis Using Dictyostelium discoideum
Tania Jauslin,a Otmane Lamrabet,a Xenia Crespo-Yañez,a Anna
Marchetti,a Imen Ayadi,a Estelle Ifrid,a Cyril Guilhen,a Matthias
Leippe,b Pierre Cosson,a
aDepartment of Cell Physiology and Metabolism, Faculty of
Medicine, University of Geneva, Geneva, Switzerland
bZoological Institute, Comparative Immunobiology, University of
Kiel, Kiel, Germany
Tania Jauslin, Otmane Lamrabet, and Xenia Crespo-Yañez
contributed equally to this article.
mBio 2021, e03169-20, in press
ABSTRACT Ingestion and killing of bacteria by phagocytic cells
protect the human body against infections. While many mechanisms
have been proposed to account for bacterial killing in phagosomes,
their relative importance, redundancy, and specificity remain
unclear. In this study, we used the Dictyostelium discoideum amoeba
as a model phagocyte and quantified the requirement of 11 individual
gene products, including nine putative effectors, for the killing of
bacteria. This analysis revealed that radically different mechanisms
are required to kill Klebsiella pneumoniae, Escherichia coli,
Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus
subtilis. AlyL, a lysozyme-like protein equipped with a distinct
bacteriolytic region, plays a specific role in the intracellular killing
of K. pneumoniae, with assistance from BpiC and Aoah, two
lipopolysaccharide(LPS)-binding proteins. Rapid killing of E. coli
and P. aeruginosa requires the presence of BpiC and of the NoxA
NADPH oxidase. No single effector tested is essential for rapid
killing of S. aureus or B. subtilis. Overall, our observations
reveal an unsuspected degree of specificity in the elimination of
bacteria in phagosomes.
IMPORTANCE Phagocytic cells ingest and kill bacteria, a process
essential for the defense of the human body against infections.
Many potential killing mechanisms have been identified in
phagocytic cells, including free radicals, toxic ions, enzymes,and
permeabilizing peptides. Yet fundamental questions remain
unanswered: what is the relative importance of these mechanisms,
how redundant are they, and are different mechanisms used to kill
different species of bacteria? We addressed these questions using
Dictyostelium discoideum, a model phagocytic cell amenable to
genetic manipulations and quantitative analysis. Our results reveal
that vastly different mechanisms are required to kill different species
of bacteria. This very high degree of specificity was unexpected and
indicates that a lot remains to be discovered about how phagocytic
cells eliminate bacteria.
submitted by: Otmane Lamrabet [[log in to unmask]]
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