Link to the paper: https://www.frontiersin.org/…/fcimb.2022.705647/full
The study investigates the impact of LSMMG culture on the interaction between Salmonella Typhimurium and a 3-D model of human intestinal tissue, revealing fewer transcriptional differences between LSMMG and control-infected host cells when infected with the Dhfq mutant strain compared to the wild type strain.
These findings provide insights into how physical forces, such as LSMMG, can affect the early stages of human enteric salmonellosis.
Contributions of the paper
Investigates the effect of LSMMG culture on the interaction between Salmonella Typhimurium and a 3-D model of human intestinal tissue, providing insights into the impact of physical forces on the early stages of human enteric salmonellosis.
Profiles the colonization of LSMMG-cultured Salmonella Typhimurium in a 3-D colonic co-culture model containing macrophages, using a transcriptomic approach to obtain a global view of the dynamics of infection at a molecular level.
Reveals that LSMMG culture alters the global transcriptomic and proteomic profiles of both uninfected and infected host cells, indicating the potential for a heightened spaceflight infection and aligning with the observed increase in virulence in mice during spaceflight.
Provides valuable information on the virulence trends of Salmonella following spaceflight and the relevance of low fluid shear suspension culture environment in understanding the behavior of enteric pathogens in the intestinal tract.
Practical implications of the paper
Understanding the impact of LSMMG culture on the interaction between Salmonella Typhimurium and human intestinal tissue can provide insights into the behavior of enteric pathogens in the intestinal tract, particularly in spaceflight conditions.
The findings highlight the potential for a heightened infection and increased virulence of Salmonella during spaceflight, indicating the need for appropriate measures to prevent and control infections in astronauts.
The study emphasizes the importance of considering physical forces, such as LSMMG, in studying host-pathogen interactions and developing strategies to mitigate the risk of enteric salmonellosis.
The use of a 3-D biomimetic intestinal co-culture model provides a valuable tool for studying the dynamics of infection at a molecular level and evaluating the efficacy of potential therapeutics or preventive measures.
The identification of specific genes involved in adherence, invasion, and motility/chemotaxis that are commonly upregulated under LSMMG conditions can inform the development of targeted interventions to disrupt these processes and reduce the virulence of Salmonella infections.
Methods used in this paper
Human colonic epithelial cell line HT-29 and human monocytic cell line U937 were cultured in GTSF-2 medium supplemented with heat-inactivated FBS, ITS, and sodium bicarbonate .
Wild type S. Typhimurium c3339 and an isogenic Dhfq mutant derivative of c3339 were used for infection studies .
Escherichia coli (E.coli) HB101 was used as a non-invasive control for infection studies .
Bacteria were cultured in Lennox Broth for all experiments .
The interaction between Salmonella Typhimurium and a 3-D model of human intestinal tissue was studied using a transcriptomic approach to analyze the global transcriptomic and proteomic profiles of infected host cells .
The colonization of LSMMG-cultured Salmonella Typhimurium in the 3-D colonic co-culture model containing macrophages was assessed .
Note: The provided sources do not provide detailed information on the methods used in the paper. The information provided is a summary of the methods mentioned in the sources.
Data used in this paper
The study used a 3-D biomimetic intestinal co-culture model of human intestinal tissue to investigate the interaction between Salmonella Typhimurium and host cells.
Transcriptomic analysis was performed to analyze the global gene expression profiles of infected host cells.
The study compared the transcriptional differences between LSMMG-infected host cells and control-infected host cells, both with wild type and Dhfq mutant strains of Salmonella Typhimurium.
The study also examined the expression levels of specific genes, such as zirTS (zinc regulated transporter) and histone genes, in response to LSMMG culture.
Previous studies using the same 3-D co-culture model infected with S. Typhimurium were referenced to compare the virulence and gene expression profiles of the pathogen.
Note: The provided sources do not provide detailed information on the specific data collection methods used in the paper. The information provided is a summary of the data mentioned in the sources.
Results of the paper
The study found that LSMMG culture had an impact on the interaction between Salmonella Typhimurium and a 3-D model of human intestinal tissue, leading to fewer transcriptional differences between LSMMG-infected host cells and control-infected host cells with the wild type strain .
Transcriptomic analysis revealed that LSMMG culture of S. Typhimurium resulted in differential expression of genes associated with motility, chemotaxis, pathogenesis, TCA cycle, cell adhesion, pilus organization, flagellar assembly, and chemotaxis .
Upregulation of genes associated with adherence, invasion, and motility was observed in LSMMG culture, including genes within Salmonella Pathogenicity Island (SPI)-1 and SPI-5 .
Downregulation of genes associated with intracellular survival and host transmission was observed in LSMMG culture, including sitABCD, several SPI-2-associated genes, and plasmid-encoded transcripts .
The study also suggested that LSMMG culture may prime the wild type pathogen for attachment and invasion in the early stages of infection, while control cultures may be better adapted for intracellular survival and host-to-host transmission .
Note: The provided sources do not provide a comprehensive summary of the results. The information provided is a summary of the results mentioned in the sources.
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