scholarly journals Chronic Salmonella enterica Serovar Typhimurium-Induced Colitis and Cholangitis in Streptomycin-Pretreated Nramp1+/+ Mice

2006 ◽  
Vol 74 (9) ◽  
pp. 5047-5057 ◽  
Author(s):  
Bärbel Stecher ◽  
Günther Paesold ◽  
Manja Barthel ◽  
Marcus Kremer ◽  
Jonathan Jantsch ◽  
...  
Keyword(s):  
Side Effects ◽  
Salmonella Enterica ◽  
Chronic Infection ◽  
Initial Phase ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Bacterial Pathogen ◽  
Mouse Strains ◽  
Acute Colitis ◽  
Duct Epithelium ◽  
Serovar Typhimurium

ABSTRACT Salmonella enterica subspecies 1 serovar Typhimurium is an enteric bacterial pathogen infecting a broad range of hosts. In susceptible Nramp1 − / − (Slc11α1 − / −) mice, serovar Typhimurium cannot efficiently colonize the intestine but causes a systemic typhoid-like infection. However, after pretreatment with streptomycin, these susceptible (C57BL/6 and BALB/c) mice develop acute serovar Typhimurium-induced colitis (M. Barthel et al., Infect. Immun. 71:2839-2858, 2003). It was not clear whether resistant Nramp1 +/+ (Slc11α1 +/+) mouse strains would similarly develop colitis. Here we compared serovar Typhimurium infection in streptomycin-pretreated susceptible (C57BL/6) and resistant (DBA/2 and 129Sv/Ev) mouse strains: We found that acute colitis (days 1 and 3 postinfection) is strikingly similar in susceptible and resistant mice. In 129Sv/Ev mice we followed the serovar Typhimurium infection for as long as 6 weeks. After the initial phase of acute colitis, these animals developed chronic crypt-destructive colitis, including ulceration, crypt abscesses, pronounced mucosal and submucosal infiltrates, overshooting regeneration of the epithelium, and crypt branching. Moreover, we observed inflammation of the gall duct epithelium (cholangitis) in the 129Sv/Ev mice between days 14 and 43 of infection. Cholangitis was not attributable to side effects of the streptomycin treatment. Furthermore, chronic infection of 129Sv/Ev mice in a typhoid fever model did not lead to cholangitis. We propose that streptomycin-pretreated 129Sv/Ev mice provide a robust murine model for chronic enteric salmonellosis including complications such as cholangitis.

scholarly journals Abelson Tyrosine Kinase Facilitates Salmonella enterica Serovar Typhimurium Entry into Epithelial Cells

2008 ◽  
Vol 77 (1) ◽  
pp. 60-69 ◽  
Author(s):  
Kim Thien Ly ◽  
James E. Casanova
Keyword(s):  
Tyrosine Kinase ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Bacterial Pathogen ◽  
Adaptor Protein ◽  
Effector Proteins ◽  
Interacting Protein ◽  
Abelson Tyrosine Kinase ◽  
System A ◽  
Serovar Typhimurium

ABSTRACT The intracellular gram-negative bacterial pathogen Salmonella enterica serovar Typhimurium gains entry into nonphagocytic cells by manipulating the assembly of the host actin cytoskeleton. S. enterica serovar Typhimurium entry requires a functional type III secretion system, a conduit through which bacterial effector proteins are directly translocated into the host cytosol. We and others have previously reported the enhancement of tyrosine kinase activities during Salmonella serovar Typhimurium infection; however, neither specific kinases nor their targets have been well characterized. In this study, we investigated the roles of the cellular Abelson tyrosine kinase (c-Abl) and the related protein Arg in the context of serovar Typhimurium infection. We found that bacterial internalization was inhibited by more than 70% in cells lacking both c-Abl and Arg and that treatment of wild-type cells with a pharmaceutical inhibitor of the c-Abl kinase, STI571 (imatinib), reduced serovar Typhimurium invasion efficiency to a similar extent. Bacterial infection led to enhanced phosphorylation of two previously identified c-Abl substrates, the adaptor protein CT10 regulator of kinase (CrkII) and the Abelson-interacting protein Abi1, a component of the WAVE2 complex. Furthermore, overexpression of the nonphosphorylatable form of CrkII resulted in decreased invasion. Taken together, these findings indicate that c-Abl is activated during S. enterica serovar Typhimurium infection and that its phosphorylation of multiple downstream targets is functionally important in bacterial internalization.

Genomic heterogeneity of Salmonella enterica serovar Typhimurium bacteriuria from chronic infection

2017 ◽  
Vol 51 ◽  
pp. 17-20
Author(s):  
Sophie Octavia ◽  
Qinning Wang ◽  
Mark M. Tanaka ◽  
Vitali Sintchenko ◽  
Ruiting Lan
Keyword(s):  
Salmonella Enterica ◽  
Chronic Infection ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Serovar Typhimurium

scholarly journals Antibiotic control of tumor-colonizing Salmonella enterica serovar Typhimurium

2011 ◽  
Vol 236 (11) ◽  
pp. 1282-1290 ◽  
Author(s):  
Katja Crull ◽  
Siegfried Weiss
Keyword(s):  
Antibiotic Treatment ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Tumor Therapy ◽  
Bacterial Pathogen ◽  
Systemic Administration ◽  
Antitumor Effects ◽  
Serovar Typhimurium ◽  
Antibiotic Control ◽  
Complete Tumor

Systemic administration of Salmonella enterica serovar Typhimurium ( S. typhimurium) into tumor-bearing mice results in preferential colonization of tumors and causes shrinkage and sometimes complete tumor clearance. However, in spite of these beneficial antitumor effects, the systemic administration of a bacterial pathogen raises serious safety concerns as well. Addressing those concerns, here, we demonstrate that tumor-colonizing Salmonella can be readily controlled by systemic administration of the antibiotic – ciprofloxacin. Treatment was most effective when started early postinfection. This was achieved at the expense of the efficacy of tumor therapy. In many of the mice treated in such a way, tumors re-grew again. Nevertheless, some mice were able to clear the tumor despite the start of antibiotic treatment only 24 h after the start of infection. Furthermore, we could demonstrate that such mice had elicited a specific antitumor immune response. Thus, S. typhimurium-mediated tumor therapy might be applied safely when combined with early antibiotic treatment. However, the therapeutic power of the bacteria needs to be enhanced in order to provide a more effective therapeutic tool.

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