dictyNews
Electronic Edition
Volume 41, number 23
October 31, 2015

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=========
Abstracts
=========

Reactive oxygen species and mitochondria: A nexus of cellular 
homeostasis.

Dan Dunn J1, Alvarez LA2, Zhang X3, Soldati T4.

1Department of Biochemistry, University of Geneva, 30 quai 
Ernest Ansermet, Sciences II, CH-1211 Genève-4, Switzerland. 
2National Children's Research Centre, Our Lady's Children's 
Hospital, Crumlin, Dublin 12, Ireland. 
3Department of Biochemistry, University of Geneva, 30 quai 
Ernest Ansermet, Sciences II, CH-1211 Genève-4, Switzerland. 
4Department of Biochemistry, University of Geneva, 30 quai 
Ernest Ansermet, Sciences II, CH-1211 Genève-4, Switzerland. 


In: Redox Biol. 2015 Sep 10;6:472-485.

Reactive oxygen species (ROS) are integral components of 
multiple cellular pathways even though excessive or 
inappropriately localized ROS damage cells. ROS function as 
anti-microbial effector molecules and as signaling molecules 
that regulate such processes as NF-kB transcriptional activity, 
the production of DNA-based neutrophil extracellular traps 
(NETs), and autophagy. The main sources of cellular ROS are 
mitochondria and NADPH oxidases (NOXs). In contrast to 
NOX-generated ROS, ROS produced in the mitochondria 
(mtROS) were initially considered to be unwanted by-products 
of oxidative metabolism. Increasing evidence indicates that 
mtROS have been incorporated into signaling pathways including 
those regulating immune responses and autophagy. As metabolic 
hubs, mitochondria facilitate crosstalk between the metabolic 
state of the cell with these pathways. Mitochondria and ROS 
are thus a nexus of multiple pathways that determine the 
response of cells to disruptions in cellular homeostasis such 
as infection, sterile damage, and metabolic imbalance. In this 
review, we discuss the roles of mitochondria in the generation 
of ROS-derived anti-microbial effectors, the interplay of 
mitochondria and ROS with autophagy and the formation of DNA 
extracellular traps, and activation of the NLRP3 inflammasome 
by ROS and mitochondria.


Submitted by Thierry Soldati [[log in to unmask]]  
————————————————————————————————————


Charged Solvatochromic Dyes as Signal Transducers in pH 
Independent Fluorescent and Colorimetric Ion Selective 
Nanosensors.

Xie X1, Gutiérrez A1,2, Trofimov V2, Szilagyi I1, 
Soldati T2, Bakker E1.

1Department of Inorganic and Analytical Chemistry, University 
of Geneva , Quai Ernest-Ansermet 30, CH-1211, Geneva, 
Switzerland.
2Department of Biochemistry, University of Geneva , Quai 
Ernest-Ansermet 30, CH-1211, Geneva, Switzerland.


In: Anal Chem. 2015 Oct 6;87(19):9954-9.

Ionophore-based ion selective optical nanosensors that operate 
independently of the sample pH are developed here by the use 
of electrically charged solvatochromic dyes as signal 
transducers. A series of dye molecules with a D-pi-A structure 
was synthesized and characterized in various solvents and 
incorporated into ion selective nanospheres for K(+), Na(+), 
and H(+). Since dye leakage was greatly suppressed when the 
solvatochromic dyes were encapsulated in the nanosphere core, 
ion sensing nanospheres were explored for cellular ion imaging 
in Dictyostelium discoideum live cells but spontaneous dye 
loss resulted in undesired staining of cells. The in vitro analysis 
of potassium in human plasma was successfully demonstrated 
with this approach. A theoretical model was developed for the 
response of the ion selective nanosensors containing charged 
solvatochromic dyes. The nanosensors exhibited a tunable 
response range, high sensitivity, and good stability.


Submitted by Thierry Soldati [[log in to unmask]] 
———————————————————————————————————————


Adrenergic antagonists restrict replication of Legionella.

Harrison CF1, Kicka S2, Kranjc A3, Finsel I1, Chiriano G3, 
Ouertatani-Sakouhi H4, Soldati T2, Scapozza L3, Hilbi H5.

1 Max von Pettenkofer Institute, Department of Medicine, 
Ludwig-Maximilians University Munich, 80336 Munich, Germany.
2 Department of Biochemistry, University of Geneva, 1211 
Geneva, Switzerland.
3 School of Pharmaceutical Sciences, Department of 
Pharmaceutical Biochemistry, University of Geneva and 
University of Lausanne, 1211 Geneva, Switzerland.
4 Faculty of Medicine, University of Geneva, 1211 Geneva, 
Switzerland. 
5 Institute of Medical Microbiology, Department of Medicine, 
University of Zurich, Gloriastrasse 30/32, 8006 Zurich, 
Switzerland.


In: Microbiology. 2015 Jul;161(7):1392-406

Legionella pneumophila is a facultative intracellular bacterium, 
which upon inhalation can cause a potentially fatal pneumonia 
termed Legionnaires' disease. The opportunistic pathogen grows 
in environmental amoebae and mammalian macrophages within a 
unique membrane-bound compartment, the 'Legionella-containing 
vacuole'. Bacteria are exposed to many environmental cues 
including small signalling molecules from eukaryotic cells. A 
number of pathogenic bacteria sense and respond to catecholamine 
hormones, such as adrenalin and noradrenalin, a process mediated 
via the QseBC two-component system in some bacteria. In this 
study, we examined the effect of adrenergic compounds on 
L. pneumophila, and discovered that the adrenergic receptor 
antagonists benoxathian, naftopidil, propranolol and labetalol, as 
well as the QseC sensor kinase inhibitor LED209, reduced the 
growth of L. pneumophila in broth or amoebae, while replication 
in macrophages was enhanced. Growth restriction was common to 
members of the genus Legionella and Mycobacterium, and was 
observed for L. pneumophila in the replicative but not stationary 
phase of the biphasic life cycle. Deletion of the L. pneumophila 
qseBC genes indicated that growth inhibition by adrenergics or 
LED209 is mediated only to a minor extent by this two-component 
system, implying the presence of other adrenergic sensing systems. 
This study identifies adrenergic molecules as novel inhibitors of 
extra- and intracellular growth of Legionella and reveals LED209 
as a potential lead compound to combat infections with Legionella 
or Mycobacterium spp.


Submitted by Thierry Soldati [[log in to unmask]] 
———————————————————————————————————————


Live imaging of Mycobacterium marinum infection in Dictyostelium 
discoideum.

Barisch C1, López-Jiménez AT, Soldati T.

1Département de Biochimie, Faculté des Sciences, Université de 
Genève, Sciences II, 30 Quai Ernest Ansermet, 1211, Genève-4, 
Switzerland.


In; Methods Mol Biol. 2015;1285:369-85: 

The Dictyostelium discoideum-Mycobacterium marinum host-pathogen 
system is a recently established and powerful model system for 
mycobacterial infection. In this chapter, two simple protocols for 
live imaging of Dictyostelium discoideum infection are described. 
The first method is used to monitor the dynamics of recruitment of 
GFP-tagged Dictyostelium discoideum proteins at single time-points 
corresponding to the main stages of the infection (1.5-72 h post 
infection). The second method focuses at the early stages of the 
establishment of an infection (0-3 h post infection). In addition, 
several procedures to improve the imaging of the bacterium-
containing compartment are described. Basic bacterial parameters 
such as bacterial growth and the recruitment of host proteins to 
the bacterium-containing compartment can be easily and precisely 
quantified using macros for ImageJ. These methods can be adapted 
to monitoring mycobacteria infection in other systems using
 mammalian cells.


Submitted by Thierry Soldati [[log in to unmask]] 
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[End dictyNews, volume 41, number 23]