scholarly journals Reducing Mortality in Salmonella enterica Serovar Typhimurium-Infected Mice with a Tripeptidic Serum Fraction

2002 ◽  
Vol 46 (6) ◽  
pp. 1971-1973 ◽  
Author(s):  
Todd A. Parker ◽  
Kenneth O. Willeford ◽  
Suzanne Parker ◽  
Karyl Buddington

ABSTRACT Salmonellosis-induced mortality in female Swiss Webster mice decreased significantly when tripeptidic immunostimulant (TPI) was administered prophylactically. Prophylactic benefits developed in a dose-dependent manner wherein 15 mg of TPI given 1 day before challenge reduced mortality by 70%.

2012 ◽  
Vol 56 (12) ◽  
pp. 6407-6409 ◽  
Author(s):  
Muhammad A. Soofi ◽  
Mohamed N. Seleem

ABSTRACTWe investigated the capability of antisense peptide nucleic acids (PNAs) conjugated to the (KFF)3K cell-penetrating peptide to target possible essential genes (ligA,rpoA,rpoD,engA,tsf, andkdtA) inSalmonella entericaserovar Typhimurium and inhibit bacterial growthin vitro and in cell culture. All targeted PNA-based gene inhibition has shown great potency in gene expression inhibition in a sequence-specific and dose-dependent manner at micromolar concentrations. Among tested PNAs, the anti-rpoAand -rpoDPNAs showed the greatest potency.


2013 ◽  
Vol 165 (3-4) ◽  
pp. 373-377 ◽  
Author(s):  
John Elmerdahl Olsen ◽  
Kirsten Hobolt Hoegh-Andersen ◽  
Jesper Tjørnholt Rosenkrantz ◽  
Casper Schroll ◽  
Josep Casadesús ◽  
...  

2002 ◽  
Vol 184 (14) ◽  
pp. 3774-3784 ◽  
Author(s):  
Maya Elgrably-Weiss ◽  
Sunny Park ◽  
Eliana Schlosser-Silverman ◽  
Ilan Rosenshine ◽  
James Imlay ◽  
...  

ABSTRACT The first committed step in the biosynthesis of heme, an important cofactor of two catalases and a number of cytochromes, is catalyzed by the hemA gene product. Salmonella enterica serovar Typhimurium hemA26::Tn10d (hemA26) was identified in a genetic screen of insertion mutants that were sensitive to hydrogen peroxide. Here we show that the hemA26 mutant respires at half the rate of wild-type cells and is highly susceptible to the effects of oxygen species. Exposure of the hemA26 strain to hydrogen peroxide results in extensive DNA damage and cell death. The chelation of intracellular free iron fully abrogates the sensitivity of this mutant, indicating that the DNA damage results from the iron-catalyzed formation of hydroxyl radicals. The inactivation of heme synthesis does not change the amount of intracellular iron, but by diminishing the rate of respiration, it apparently increases the amount of reducing equivalents available to drive the Fenton reaction. We also report that hydrogen peroxide has opposite effects on the expression of hemA and hemH, the first and last genes of heme biosynthesis pathway, respectively. hemA mRNA levels decrease, while the transcription of hemH is induced by hydrogen peroxide, in an oxyR-dependent manner. The oxyR-dependent induction is suppressed under conditions that accelerate the Fenton reaction by a mechanism that is not yet understood.


2021 ◽  
Author(s):  
Dominika Houserova ◽  
Yulong Huang ◽  
Kasukurthi Kasukurthi ◽  
Brianna Watters ◽  
Fiza Khan ◽  
...  

Abstract Salmonella Outer Membrane Vesicles (OMVs) were recently shown to inhibit P22 bacteriophage infection. Interestingly, we identify 31 recurrent tRFs abundantly expressed by Salmonella enterica serovar Typhimurium and find these tRFs are highly complementary to known Salmonella enterica-infecting bacteriophage (17 averaging 97.4% complementarity over 22.9 nt) and specifically enriched in S. Typhimurium OMVs. Most notably, tRNA-Thr-CGT-1-1, 44-73, bears 100% complementary over its entire 30 nt length to 29 distinct Salmonella enterica-infecting bacteriophage including P22. Importantly, we find inhibiting this tRF in secreted OMVs improves P22 infectivity in a dose dependent manner whereas raising OMV tRF levels conversely inhibits P22. Furthermore, we find P22 pre-incubation with OMVs isolated from naïve S. Typhimurium, rescues the ability of S. Typhimurium depleted of tRNA-Thr-CGT-1-1, 44-73 tRF to defend against P22. Collectively, these experiments confirm tRFs secreted in S. Typhimurium OMVs are directly involved with and required for the ability of OMVs to defend against bacteriophage predation. As we find the majority of OMV tRFs are highly complementary to an array of known Salmonella enterica-infecting bacteriophage, we suggest OMV tRFs may primarily function as a broadly acting, previously uncharacterized ancient antiviral defense.


2002 ◽  
Vol 70 (9) ◽  
pp. 5312-5315 ◽  
Author(s):  
Laura M. Sly ◽  
Donald G. Guiney ◽  
Neil E. Reiner

ABSTRACT Vitamin D3 (1,25-dihydroxycholecalciferol) induced the phagocyte oxidative burst and intracellular killing of Salmonella enterica serovar Typhimurium in a phosphatidylinositol 3-kinase-dependent manner. The antimicrobial effect was more pronounced for Salmonella SodCI and SodCII mutants, confirming the role of the phagocyte oxidase in the vitamin D3 effect. The results for an in vitro system with human THP-1 cells correlate with in vivo virulence data for mice and show that both the SodCI and SodCII enzymes are required to protect against the oxidative burst.


2006 ◽  
Vol 189 (5) ◽  
pp. 1589-1596 ◽  
Author(s):  
Yu Liu ◽  
Nicole A. Leal ◽  
Edith M. Sampson ◽  
Celeste L. V. Johnson ◽  
Gregory D. Havemann ◽  
...  

ABSTRACT Salmonella enterica degrades 1,2-propanediol (1,2-PD) in a coenzyme B12-dependent manner. Previous enzymatic assays of crude cell extracts indicated that a phosphotransacylase (PTAC) was needed for this process, but the enzyme involved was not identified. Here, we show that the pduL gene encodes an evolutionarily distinct PTAC used for 1,2-PD degradation. Growth tests showed that pduL mutants were unable to ferment 1,2-PD and were also impaired for aerobic growth on this compound. Enzyme assays showed that cell extracts from a pduL mutant lacked measurable PTAC activity in a background that also carried a pta mutation (the pta gene was previously shown to encode a PTAC enzyme). Ectopic expression of pduL corrected the growth defects of a pta mutant. PduL fused to eight C-terminal histidine residues (PduL-His8) was purified, and its kinetic constants were determined: the V max was 51.7 ± 7.6 μmol min−1 mg−1, and the Km values for propionyl-PO4 2− and acetyl-PO4 2− were 0.61 and 0.97 mM, respectively. Sequence analyses showed that PduL is unrelated in amino acid sequence to known PTAC enzymes and that PduL homologues are distributed among at least 49 bacterial species but are absent from the Archaea and Eukarya.


2021 ◽  
Author(s):  
Dominika Houserova ◽  
Yulong Huang ◽  
Mohan V. Kasukurthi ◽  
Brianna C. Watters ◽  
Fiza F. Khan ◽  
...  

Salmonella Outer Membrane Vesicles (OMVs) were recently shown to inhibit P22 bacteriophage infection. Furthermore, despite there being several published reports now independently describing (1) the marked prevalence of tRFs within secreted vesicle transcriptomes and (2) roles for specific tRFs in facilitating/inhibiting viral replication, there have been no examinations of the effects of vesicle-secreted tRFs on viral infection reported to date. Notably, while specific tRFs have been reported in a number of bacteria, the tRFs expressed by salmonellae have not been previously characterized. As such, we recently screened small RNA-seq datasets for the presence of recurrent, specifically excised tRFs and identified 31 recurrent, relatively abundant tRFs expressed by Salmonella enterica serovar Typhimurium (SL1344). Furthermore, we find S. Typhimurium OMVs contain significant levels of tRFs highly complementary to known Salmonella enterica-infecting bacteriophage with 17 of 31 tRFs bearing marked complementarity to at least one known Salmonella enterica-infecting phage (averaging 97.4% complementarity over 22.9 nt). Most notably, tRNA-Thr-CGT-1-1, 44-73, bears 100% sequence complementary over its entire 30 nt length to 29 distinct, annotated Salmonella enterica-infecting bacteriophage including P22. Importantly, we find inhibiting this tRF in secreted OMVs improves P22 infectivity in a dose dependent manner whereas raising OMV tRF levels conversely inhibits P22 infectivity. Furthermore, we find P22 phage pre-incubation with OMVs isolated from naive, control SL1344 S. Typhimurium, successfully rescues the ability of S. Typhimurium transformed with a specific tRNA-Thr-CGT-1-1, 44-73 tRF inhibitor to defend against P22. Collectively, these experiments confirm tRFs secreted in S. Typhimurium OMVs are directly involved with and required for the ability of OMVs to defend against bacteriophage predation. As we find the majority of OMV tRFs are highly complementary to an array of known Salmonella enterica-infecting bacteriophage, we suggest OMV tRFs may primarily function as a broadly acting, previously uncharacterized innate antiviral defense.


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