Dataset Information

Synergistic action of SPI-1 gene expression in Salmonella enterica serovar typhimurium through transcriptional crosstalk with the flagellar system.

ABSTRACT:

Background

Salmonella enterica serovar Typhimurium is a common food-borne pathogen. S. enterica uses a type III secretion system encoded within Salmonella pathogenicity island 1 (SPI-1) to invade intestinal epithelial cells. A complex network of interacting transcription factors regulates SPI-1 gene expression. In addition, SPI-1 gene expression is coupled to flagellar gene expression. Both SPI-1 and flagellar gene expression are bistable, with co-existing populations of cells expressing and not expressing these genes. Previous work demonstrated that nutrients could be used to tune the fraction of cells expressing the flagellar genes. In the present study, we tested whether nutrients could also tune the fraction of cells expressing the SPI-1 genes through transcriptional crosstalk with the flagellar genes.

Results

Nutrients alone were not found to induce SPI-1 gene expression. However, when the cells were also grown in the presence of acetate, the concentration of nutrients in the growth medium was able to tune the fraction of cells expressing the SPI-1 genes. During growth in nutrient-poor medium, acetate alone was unable to induce SPI-1 gene expression. These results demonstrate that acetate and nutrients synergistically activate SPI-1 gene expression. The response to acetate was governed by the BarA/SirA two-component system and the response to nutrients was governed by transcriptional crosstalk with the flagella system, specifically through the action of the flagellar regulator FliZ.

Conclusions

Acetate and nutrients are capable of synergistically activating SPI-1 gene expression. In addition, these signals were found to tune the fraction of cells expressing the SPI-1 genes. The governing mechanism involves transcriptional crosstalk with the flagellar gene network. Collectively, these results further our understanding of SPI-1 gene regulation and provide the basis for future studies investigating this complex regulatory mechanism.

SUBMITTER: Hamed S

PROVIDER: S-EPMC6727558 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Publications

Synergistic action of SPI-1 gene expression in Salmonella enterica serovar typhimurium through transcriptional crosstalk with the flagellar system.

Hamed Selwan S Wang Xiaoyi X Shawky Riham M RM Emara Mohamed M Aldridge Philip D PD Rao Christopher V CV

BMC microbiology 20190905 1

<h4>Background</h4>Salmonella enterica serovar Typhimurium is a common food-borne pathogen. S. enterica uses a type III secretion system encoded within Salmonella pathogenicity island 1 (SPI-1) to invade intestinal epithelial cells. A complex network of interacting transcription factors regulates SPI-1 gene expression. In addition, SPI-1 gene expression is coupled to flagellar gene expression. Both SPI-1 and flagellar gene expression are bistable, with co-existing populations of cells expressing ...[more]

PMID: 31488053

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Project description:BACKGROUND:The antibiotics generally used in farm animals are rapidly losing their effectiveness all over the world as bacteria develop antibiotic resistance. Like some other pathogenic bacteria multidrug-resistant strains of Salmonella enterica serovar Typhimurium (S. Typhimurium) are also frequently found in animals and humans which poses a major public health concern. New strategies are needed to block the development of resistance and to prolong the life of traditional antibiotics. Thus, this study aimed to increase the efficacy of existing antibiotics against S. Typhimurium by combining them with opportunistic phenolic compounds gallic acid (GA), epicatechin, epicatechin gallate, epigallocatechin and hamamelitannin. Fractional inhibitory concentration indexes (FICI) of phenolic compound-antibiotic combinations against S. Typhimurium were determined. Based on the FICI and clinical importance, 1 combination (GA and ceftiofur) was selected for evaluating its effects on the virulence factors of this bacterium. Viability of Rattus norvegicus (IEC-6) cell in presence of this antibacterial combination was evaluated. RESULTS:Minimum inhibitory concentrations (MICs) of GA, epigallocatechin and hamamelitannin found against different strains of S. Typhimurium were 256, (512-1024), and (512-1024) ?g/mL, respectively. Synergistic antibacterial effect was obtained from the combination of erythromycin-epicatechin gallate (FICI: 0.50) against S. Typhimurium. Moreover, additive effects (FICI: 0.502-0.750) were obtained from 16 combinations against this bacterium. The time-kill assay and ultrastructural morphology showed that GA-ceftiofur combination more efficiently inhibited the growth of S. Typhimurium compared to individual antimicrobials. Biofilm viability, and swimming and swarming motilities of S. Typhimurium in presence of GA-ceftiofur combination were more competently inhibited than individual antimicrobials. Viabilities of IEC-6 cells were more significantly enhanced by GA-ceftiofur combinations than these antibacterials alone. CONCLUSIONS:This study suggests that GA-ceftiofur combination can be potential medication to treat S. Typhimurium-associated diarrhea and prevent S. Typhimurium-associated blood-stream infections (e.g.: fever) in farm animals, and ultimately its transmission from animal to human. Further in vivo study to confirm these effects and safety profiles in farm animal should be undertaken for establishing these combinations as medications.

Dataset Information

Synergistic action of SPI-1 gene expression in Salmonella enterica serovar typhimurium through transcriptional crosstalk with the flagellar system.

Background

Results

Conclusions

Publications

Synergistic action of SPI-1 gene expression in Salmonella enterica serovar typhimurium through transcriptional crosstalk with the flagellar system.

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