Thioridazine protects the mouse from a virulent infection by Salmonella enterica serovar Typhimurium 74
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Thioridazine protects the mouse from a virulent infection by Salmonella enterica serovar Typhimurium 74. / Dasgupta, Asish; Mukherjee, Sayanti; Chaki, Shaswati; Dastidar, Sujata G; Hendricks, Oliver; Christensen, Jørn B; Kristiansen, Jette E.; Amaral, Leonard.
I: International Journal of Antimicrobial Agents, Bind 35, Nr. 2, 01.02.2010, s. 174-6.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › fagfællebedømt
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TY - JOUR
T1 - Thioridazine protects the mouse from a virulent infection by Salmonella enterica serovar Typhimurium 74
AU - Dasgupta, Asish
AU - Mukherjee, Sayanti
AU - Chaki, Shaswati
AU - Dastidar, Sujata G
AU - Hendricks, Oliver
AU - Christensen, Jørn B
AU - Kristiansen, Jette E.
AU - Amaral, Leonard
N1 - Copyright 2009 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
PY - 2010/2/1
Y1 - 2010/2/1
N2 - When administered to mice at doses of 100microg/mouse and 200microg/mouse, thioridazine (TDZ) significantly protected animals from the lethality produced by a virulent strain of Salmonella enterica serovar Typhimurium and reduced the number of bacteria retrieved from the spleen, liver and heart blood. The protection conferred by TDZ against a virulent Salmonella infection is hypothesised to be due to a reduction in the 55kDa virulence protein of the outer membrane of the organism, as this protein is almost totally absent when the organism is exposed to the phenothiazine. It is further hypothesised that the reduction in the 55kDa virulence factor renders the organism susceptible to the action of hydrolytic enzymes of the neutrophil phagolysosome, whereas in the absence of exposure to TDZ intracellular ingestion and localisation of the phagocytosed bacterium does not result in killing owing to rapid induction of the two-step PmrA/B regulon that results in the eventual synthesis and insertion of lipid A into the nascent lipopolysaccharide layer of the outer membrane.
AB - When administered to mice at doses of 100microg/mouse and 200microg/mouse, thioridazine (TDZ) significantly protected animals from the lethality produced by a virulent strain of Salmonella enterica serovar Typhimurium and reduced the number of bacteria retrieved from the spleen, liver and heart blood. The protection conferred by TDZ against a virulent Salmonella infection is hypothesised to be due to a reduction in the 55kDa virulence protein of the outer membrane of the organism, as this protein is almost totally absent when the organism is exposed to the phenothiazine. It is further hypothesised that the reduction in the 55kDa virulence factor renders the organism susceptible to the action of hydrolytic enzymes of the neutrophil phagolysosome, whereas in the absence of exposure to TDZ intracellular ingestion and localisation of the phagocytosed bacterium does not result in killing owing to rapid induction of the two-step PmrA/B regulon that results in the eventual synthesis and insertion of lipid A into the nascent lipopolysaccharide layer of the outer membrane.
KW - Animals
KW - Anti-Infective Agents
KW - Antibiotic Prophylaxis
KW - Bacterial Proteins
KW - Blood
KW - Colony Count, Microbial
KW - Liver
KW - Male
KW - Mice
KW - Microbial Viability
KW - Neutrophils
KW - Salmonella Infections, Animal
KW - Salmonella typhimurium
KW - Spleen
KW - Survival Analysis
KW - Thioridazine
KW - Virulence Factors
U2 - 10.1016/j.ijantimicag.2009.09.027
DO - 10.1016/j.ijantimicag.2009.09.027
M3 - Journal article
C2 - 20005679
VL - 35
SP - 174
EP - 176
JO - International Journal of Antimicrobial Agents
JF - International Journal of Antimicrobial Agents
SN - 0924-8579
IS - 2
ER -
ID: 33247814