scholarly journals Salmonella enterica Serovar Typhimurium Requires Nonsterol Precursors of the Cholesterol Biosynthetic Pathway for Intracellular Proliferation

2004 ◽  
Vol 72 (2) ◽  
pp. 1036-1042 ◽  
Author(s):  
Drew M. Catron ◽  
Yvonne Lange ◽  
Jayme Borensztajn ◽  
Matthew D. Sylvester ◽  
Bradley D. Jones ◽  
...  
Keyword(s):  
Mouse Model ◽  
Host Cell ◽  
Bacterial Growth ◽  
Salmonella Enterica ◽  
Biosynthetic Pathway ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Bacterial Proliferation ◽  
Serovar Typhimurium ◽  
Cholesterol Biosynthetic Pathway ◽  
Intracellular Proliferation

ABSTRACT We have previously shown that Salmonella enterica serovar Typhimurium infection perturbs the host cholesterol biosynthetic pathway. Here we show that inhibiting the first step of this pathway (3-hydroxy-3-methylglutaryl coenzyme A reductase) reduces the growth of intracellular S. enterica serovar Typhimurium and has no effect on extracellular bacterial growth. Selectively inhibiting synthesis of downstream sterol components has no effect on infection, suggesting that the effect of statins on host nonsterol intermediates is detrimental to bacterial growth. Furthermore, statins also reduce bacterial proliferation in the S. enterica serovar Typhimurium mouse model. This suggests that blocking the production of nonsterol precursors in the host cell can be used to reduce infection.

scholarly journals Cystathionine β-Lyase Is Important for Virulence of Salmonella enterica Serovar Typhimurium

2004 ◽  
Vol 72 (6) ◽  
pp. 3310-3314 ◽  
Author(s):  
Linda J. Ejim ◽  
Vanessa M. D'Costa ◽  
Nadine H. Elowe ◽  
J. Concepción Loredo-Osti ◽  
Danielle Malo ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Biosynthetic Pathway ◽  
Antibacterial Agents ◽  
Antimicrobial Agents ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Systemic Infection ◽  
Bacterial Virulence ◽  
Methionine Biosynthesis ◽  
Insertional Inactivation ◽  
Serovar Typhimurium

ABSTRACT The biosynthesis of methionine in bacteria requires the mobilization of sulfur from Cys by the formation and degradation of cystathionine. Cystathionine β-lyase, encoded by metC in bacteria and STR3 in Schizosaccharomyces pombe, catalyzes the breakdown of cystathionine to homocysteine, the penultimate step in methionine biosynthesis. This enzyme has been suggested to be the target for pyridinamine antimicrobial agents. We have demonstrated, by using purified enzymes from bacteria and yeast, that cystathionine β-lyase is not the likely target of these agents. Nonetheless, an insertional inactivation of metC in Salmonella enterica serovar Typhimurium resulted in the attenuation of virulence in a mouse model of systemic infection. This result confirms a previous chemical validation of the Met biosynthetic pathway as a target for the development of antibacterial agents and demonstrates that cystathionine β-lyase is important for bacterial virulence.

scholarly journals Choice of Bacterial Growth Medium Alters the Transcriptome and Phenotype of Salmonella enterica Serovar Typhimurium

PLoS ONE ◽  
2013 ◽  
Vol 8 (5) ◽  
pp. e63912 ◽  
Author(s):  
Jessica M. A. Blair ◽  
Grace E. Richmond ◽  
Andrew M. Bailey ◽  
Al Ivens ◽  
Laura J. V. Piddock
Keyword(s):  
Growth Medium ◽  
Bacterial Growth ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Serovar Typhimurium

scholarly journals Reduced Flux through the Purine Biosynthetic Pathway Results in an Increased Requirement for Coenzyme A in Thiamine Synthesis in Salmonella enterica Serovar Typhimurium

2000 ◽  
Vol 182 (1) ◽  
pp. 236-240 ◽  
Author(s):  
Michael Frodyma ◽  
Aileen Rubio ◽  
D. M. Downs
Keyword(s):  
Salmonella Enterica ◽  
Biosynthetic Pathway ◽  
Coenzyme A ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Thiamine Pyrophosphate ◽  
Nutritional Requirement ◽  
Prior Work ◽  
Serovar Typhimurium ◽  
Thiamine Biosynthesis

ABSTRACT Work presented here establishes a connection between cellular coenzyme A (CoA) levels and thiamine biosynthesis in Salmonella enterica serovar Typhimurium. Prior work showed thatpanE mutants (panE encodes ketopantoate reductase) had a conditional requirement for thiamine or pantothenate. Data presented herein show that the nutritional requirement ofpanE mutants for either thiamine or pantothenate is manifest only when flux through the purine biosynthetic pathway is reduced. Further, the data show that under the above conditions it is the lack of thiamine pyrophosphate, and not decreased CoA levels, that directly prevents growth.

scholarly journals Disruption of the Salmonella-Containing Vacuole Leads to Increased Replication of Salmonella enterica Serovar Typhimurium in the Cytosol of Epithelial Cells

2002 ◽  
Vol 70 (6) ◽  
pp. 3264-3270 ◽  
Author(s):  
John H. Brumell ◽  
Patrick Tang ◽  
Michelle L. Zaharik ◽  
B. Brett Finlay
Keyword(s):  
Epithelial Cells ◽  
Host Cell ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Host Cells ◽  
Intracellular Pathogen ◽  
Wild Type ◽  
Vacuolar Compartment ◽  
Serovar Typhimurium ◽  
Endosomal System

ABSTRACT Salmonella enterica serovar Typhimurium is a facultative intracellular pathogen that inhabits a vacuolar compartment, called the Salmonella-containing vacuole (SCV), in infected host cells. Maintenance of the SCV is accomplished by SifA, and mutants of this Salmonella pathogenicity island 2 type III effector replicate more efficiently in epithelial cells. Here we demonstrate that enhanced replication of sifA mutants occurs in the cytosol of these cells. Increased replication of wild-type bacteria was also observed in cells treated with wortmannin or expressing Rab5 Q79L or Rab7 N125I, all of which caused a loss of SCV integrity. Our findings demonstrate the requirement of the host cell endosomal system for maintenance of the SCV and that loss of this compartment allows increased replication of serovar Typhimurium in the cytosol of epithelial cells.

scholarly journals Salmonella enterica Serovar Typhimurium ompS1 and ompS2 Mutants Are Attenuated for Virulence in Mice

2006 ◽  
Vol 74 (2) ◽  
pp. 1398-1402 ◽  
Author(s):  
Olivia Rodríguez-Morales ◽  
Marcos Fernández-Mora ◽  
Ismael Hernández-Lucas ◽  
Alejandra Vázquez ◽  
José Luis Puente ◽  
...  
Keyword(s):  
Mouse Model ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Positive Regulator ◽  
Gene Coding ◽  
Serovar Typhimurium

ABSTRACT Salmonella enterica serovar Typhimurium mutants with mutations in the ompS1 and ompS2 genes, which code for quiescent porins, were nevertheless highly attenuated for virulence in a mouse model, indicating a role in pathogenesis. Similarly, a strain with a mutation in the gene coding for LeuO, a positive regulator of ompS2, was also attenuated.

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