Abstract:Manipulation of cellular motility using a target signal can facilitate the development of biosensors or microbe-powered biorobots. Here, we engineered signal-dependent motility in Escherichia coli via the transcriptional control of a key motility gene. Without manipulating chemotaxis, signal-dependent switching of motility, either on or off, led to population-level directional movement of cells up or down a signal gradient. We developed a mathematical model that captures the behaviour of the cells, enables ide… Show more
“…Gene expression in bacteria is complex and highly controlled. The regulation of bacterial gene expression is a crucial component of bacterial survival in order for these organisms to modulate gene expression and alter phenotypic properties such as growth rate (Garmendia et al 2018) and motility (Ravichandar et al 2017). Gene expression can be controlled through a variety of promoters, physical chromosome structure, and the DNA replication machinery.…”
Gene expression in bacteria is a remarkably controlled and intricate process impacted by many factors. One such factor is the genomic position of a gene within a bacterial genome. Genes located near the origin of replication generally have a higher expression level, increased dosage, and are often more conserved than genes located farther from the origin of replication. The majority of the studies involved with these findings have only noted this phenomenon in a single gene or cluster of genes that was relocated to predetermined positions within a bacterial genome. In this work, we look at the overall expression levels from eleven bacterial data sets from Escherichia coli, Bacillus subtilis, Streptomyces, and Sinorhizobium meliloti. We have confirmed that gene expression tends to decrease when moving away from the origin of replication in majority of the replicons analysed in this study. This study sheds light on the impact of genomic location on molecular trends such as gene expression and highlights the importance of accounting for spatial trends in bacterial molecular analysis.
“…Gene expression in bacteria is complex and highly controlled. The regulation of bacterial gene expression is a crucial component of bacterial survival in order for these organisms to modulate gene expression and alter phenotypic properties such as growth rate (Garmendia et al 2018) and motility (Ravichandar et al 2017). Gene expression can be controlled through a variety of promoters, physical chromosome structure, and the DNA replication machinery.…”
Gene expression in bacteria is a remarkably controlled and intricate process impacted by many factors. One such factor is the genomic position of a gene within a bacterial genome. Genes located near the origin of replication generally have a higher expression level, increased dosage, and are often more conserved than genes located farther from the origin of replication. The majority of the studies involved with these findings have only noted this phenomenon in a single gene or cluster of genes that was relocated to predetermined positions within a bacterial genome. In this work, we look at the overall expression levels from eleven bacterial data sets from Escherichia coli, Bacillus subtilis, Streptomyces, and Sinorhizobium meliloti. We have confirmed that gene expression tends to decrease when moving away from the origin of replication in majority of the replicons analysed in this study. This study sheds light on the impact of genomic location on molecular trends such as gene expression and highlights the importance of accounting for spatial trends in bacterial molecular analysis.
“…2c). Importantly, the transcriptional upregulation of these two latter genes has been directly correlated with higher bacterial motility [55, 56]. Taken together, these results suggest that Hmm preferentially stimulate the motility machinery of EHEC cells relative to Mmm, and that these changes in chemotaxis could mediate the enhanced EHEC-induced pathogenicity we observed in the human Colon Chips.Fig.…”
BackgroundSpecies-specific differences in tolerance to infection are exemplified by the high susceptibility of humans to enterohemorrhagic Escherichia coli (EHEC) infection, whereas mice are relatively resistant to this pathogen. This intrinsic species-specific difference in EHEC infection limits the translation of murine research to human. Furthermore, studying the mechanisms underlying this differential susceptibility is a difficult problem due to complex in vivo interactions between the host, pathogen, and disparate commensal microbial communities.ResultsWe utilize organ-on-a-chip (Organ Chip) microfluidic culture technology to model damage of the human colonic epithelium induced by EHEC infection, and show that epithelial injury is greater when exposed to metabolites derived from the human gut microbiome compared to mouse. Using a multi-omics approach, we discovered four human microbiome metabolitesâ4-methyl benzoic acid, 3,4-dimethylbenzoic acid, hexanoic acid, and heptanoic acidâthat are sufficient to mediate this effect. The active human microbiome metabolites preferentially induce expression of flagellin, a bacterial protein associated with motility of EHEC and increased epithelial injury. Thus, the decreased tolerance to infection observed in humans versus other species may be due in part to the presence of compounds produced by the human intestinal microbiome that actively promote bacterial pathogenicity.ConclusionOrgan-on-chip technology allowed the identification of specific human microbiome metabolites modulating EHEC pathogenesis. These identified metabolites are sufficient to increase susceptibility to EHEC in our human Colon Chip model and they contribute to species-specific tolerance. This work suggests that higher concentrations of these metabolites could be the reason for higher susceptibility to EHEC infection in certain human populations, such as children. Furthermore, this research lays the foundation for therapeutic-modulation of microbe products in order to prevent and treat human bacterial infection.Electronic supplementary materialThe online version of this article (10.1186/s40168-019-0650-5) contains supplementary material, which is available to authorized users.
“…2C). Importantly, the transcriptional upregulation of these two latter genes has been directly correlated with higher bacterial motility [51,52]. Taken together, these results suggest that Hmm preferentially stimulate the motility machinery of EHEC cells relative to Mmm, and that these changes in chemotaxis could mediate the enhanced EHEC-induced pathogenicity we observed in the human Colon Chips.…”
Section: Human Microbiome Metabolites Stimulate Bacterial Motilitymentioning
BackgroundSpecies-specific differences in tolerance to infection are exemplified by the high susceptibility of humans to enterohemorrhagic E. coli (EHEC) infection whereas mice are relatively resistant to this pathogen. This intrinsic species-specific difference in EHEC infection limits the translation of murine research to human. Furthermore, studying the mechanisms underlying this differential susceptibility is a difficult problem due to complex in vivo interactions between the host, pathogen, and disparate commensal microbial communities.
ResultsWe utilize organ-on-a-chip (Organ Chip) microfluidic culture technology to model damage of the human colonic epithelium induced by EHEC infection, and show that epithelial injury is greater when exposed to metabolites derived from the human gut microbiome compared to mouse. Using a multi-omics approach, we discovered four human microbiome metabolites -4-methyl benzoic acid, 3,4-dimethylbenzoic acid, hexanoic acid, and heptanoic acid -that are sufficient to mediate this effect. The active human microbiome metabolites preferentially induce expression of flagellin, a bacterial protein associated with motility of EHEC and increased epithelial injury. Thus, the decreased tolerance to infection observed in humans versus other species may be due in part to the presence of compounds produced by the human intestinal microbiome that actively promote bacterial pathogenicity.
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