TY  - JOUR
A1  - Wu, Yu
A1  - Pons, Valérie
A1  - Goudet, Amélie
A1  - Panigai, Laetitia
A1  - Fischer, Annette
A1  - Herweg, Jo-Ana
A1  - Kali, Sabrina
A1  - Davey, Robert A.
A1  - Laporte, Jérôme
A1  - Bouclier, Céline
A1  - Yousfi, Rahima
A1  - Aubenque, Céline
A1  - Merer, Goulven
A1  - Gobbo, Emilie
A1  - Lopez, Roman
A1  - Gillet, Cynthia
A1  - Cojean, Sandrine
A1  - Popoff, Michel R.
A1  - Clayette, Pascal
A1  - Le Grand, Roger
A1  - Boulogne, Claire
A1  - Tordo, Noël
A1  - Lemichez, Emmanuel
A1  - Loiseau, Philippe M.
A1  - Rudel, Thomas
A1  - Sauvaire, Didier
A1  - Cintrat, Jean-Christophe
A1  - Gillet, Daniel
A1  - Barbier, Julien
T1  - ABMA, a small molecule that inhibits intracellular toxins and pathogens by interfering with late endosomal compartments
JF  - Scientific Reports
N2  - Intracellular pathogenic microorganisms and toxins exploit host cell mechanisms to enter, exert their deleterious effects as well as hijack host nutrition for their development. A potential approach to treat multiple pathogen infections and that should not induce drug resistance is the use of small molecules that target host components. We identifed the compound 1-adamantyl (5-bromo-2-methoxybenzyl) amine (ABMA) from a cell-based high throughput screening for its capacity to protect human cells and mice against ricin toxin without toxicity. This compound efciently protects cells against various toxins and pathogens including viruses, intracellular bacteria and parasite. ABMA provokes Rab7-positive late endosomal compartment accumulation in mammalian cells without affecting other organelles (early endosomes, lysosomes, the Golgi apparatus, the endoplasmic reticulum or the nucleus). As the mechanism of action of ABMA is restricted to host-endosomal compartments, it reduces cell infection by pathogens that depend on this pathway to invade cells. ABMA may represent a novel class of broad-spectrum compounds with therapeutic potential against diverse severe infectious diseases.
KW  - biology
KW  - antimicrobials
KW  - high-throughput screening
KW  - infectious diseases
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173170
VL  - 7
ER  - 
TY  - JOUR
A1  - Herweg, Jo-Ana
A1  - Hansmeier, Nicole
A1  - Otto, Andreas
A1  - Geffken, Anna C.
A1  - Subbarayal, Prema
A1  - Prusty, Bhupesh K.
A1  - Becher, Dörte
A1  - Hensel, Michael
A1  - Schaible, Ulrich E.
A1  - Rudel, Thomas
A1  - Hilbi, Hubert
T1  - Purification and proteomics of pathogen-modified vacuoles and membranes
JF  - Frontiers in Cellular and Infection Microbiology
N2  - Certain pathogenic bacteria adopt an intracellular lifestyle and proliferate in eukaryotic host cells. The intracellular niche protects the bacteria from cellular and humoral components of the mammalian immune system, and at the same time, allows the bacteria to gain access to otherwise restricted nutrient sources. Yet, intracellular protection and access to nutrients comes with a price, i.e., the bacteria need to overcome cell-autonomous defense mechanisms, such as the bactericidal endocytic pathway. While a few bacteria rupture the early phagosome and escape into the host cytoplasm, most intracellular pathogens form a distinct, degradation-resistant and replication-permissive membranous compartment. Intracellular bacteria that form unique pathogen vacuoles include Legionella, Mycobacterium, Chlamydia, Simkania, and Salmonella species. In order to understand the formation of these pathogen niches on a global scale and in a comprehensive and quantitative manner, an inventory of compartment-associated host factors is required. To this end, the intact pathogen compartments need to be isolated, purified and biochemically characterized. Here, we review recent progress on the isolation and purification of pathogen-modified vacuoles and membranes, as well as their proteomic characterization by mass spectrometry and different validation approaches. These studies provide the basis for further investigations on the specific mechanisms of pathogen-driven compartment formation.
KW  - spectrometry-based proteomics
KW  - Mycobacterium tuberculosis
KW  - Chlamydia
KW  - Salmonella
KW  - bacterium Legionella pneumophila
KW  - endocytic multivesicular bodies
KW  - phagosome maturation arrest
KW  - III secretion system
KW  - endoplasmic reticulum
KW  - Chlamydia trachomatis
KW  - Simkania negevensis
KW  - intracellular bacteria
KW  - host pathogen interactions
KW  - immuno-magnetic purification
KW  - Legionella
KW  - Mycobacterium
KW  - Simkania
KW  - pathogen vacuole
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151823
VL  - 5
IS  - 48
ER  -