Metabolic model guided CRISPRi identifies a central role for phosphoglycerate mutase in persistence.

Unlabelled: Upon nutrient starvation, serovar L2 (CTL) shifts from its normal growth to a non-replicating form, termed persistence. It is unclear if persistence reflects an adaptive response or a lack thereof. To understand this, transcriptomics data were collected for CTL grown under nutrient-replete and nutrient-starved conditions.

How Bacterial Pathogens Coordinate Appetite with Virulence.

Cells adjust growth and metabolism to nutrient availability. Having access to a variety of carbon sources during infection of their animal hosts, facultative intracellular pathogens must efficiently prioritize carbon utilization. Here, we discuss how carbon source controls bacterial virulence, with an emphasis on serovar Typhimurium, which causes gastroenteritis in immunocompetent humans and a typhoid-like disease in mice, and propose that virulence factors can regulate carbon source prioritization by modifying cellular physiology.

Bacteria require phase separation for fitness in the mammalian gut.

Therapeutic manipulation of the gut microbiota holds great potential for human health. The mechanisms bacteria use to colonize the gut therefore present valuable targets for clinical intervention. We now report that bacteria use phase separation to enhance fitness in the mammalian gut.

IL-22 alters gut microbiota composition and function to increase aryl hydrocarbon receptor activity in mice and humans.

Background: IL-22 is induced by aryl hydrocarbon receptor (AhR) signaling and plays a critical role in gastrointestinal barrier function through effects on antimicrobial protein production, mucus secretion, and epithelial cell differentiation and proliferation, giving it the potential to modulate the microbiome through these direct and indirect effects. Furthermore, the microbiome can in turn influence IL-22 production through the synthesis of L-tryptophan (L-Trp)-derived AhR ligands, creating the prospect of a host-microbiome feedback loop. We evaluated the impact IL-22 may have on the gut microbiome and its ability to activate host AhR signaling by observing changes in gut microbiome composition, function, and AhR ligand production following exogenous IL-22 treatment in both mice and humans.

Host Cell Amplification of Nutritional Stress Contributes To Persistence in Chlamydia trachomatis.

Persistence, a viable but non-replicating growth state, has been implicated in diseases caused by Chlamydia trachomatis. Starvation of distinct nutrients produces a superficially similar persistent state, implying convergence on a common intracellular environment. We employed host-pathogen dual RNA-sequencing under both iron- and tryptophan-starved conditions to systematically characterize the persistent chlamydial transcriptome and to define common contributions of the host cell transcriptional stress response in shaping the intracellular environment.

The iron-dependent repressor YtgR is a tryptophan-dependent attenuator of the trpRBA operon in Chlamydia trachomatis.

The trp operon of Chlamydia trachomatis is organized differently from other model bacteria. It contains trpR, an intergenic region (IGR), and the biosynthetic trpB and trpA open-reading frames. TrpR is a tryptophan-dependent repressor that regulates the major promoter (P), while the IGR harbors an alternative promoter (P) and an operator sequence for the iron-dependent repressor YtgR to regulate trpBA expression.

A bipartite iron-dependent transcriptional regulation of the tryptophan salvage pathway in .

During infection, pathogens are starved of essential nutrients such as iron and tryptophan by host immune effectors. Without conserved global stress response regulators, how the obligate intracellular bacterium arrives at a physiologically similar 'persistent' state in response to starvation of either nutrient remains unclear. Here, we report on the iron-dependent regulation of the tryptophan salvage pathway in Iron starvation specifically induces expression from a novel promoter element within an intergenic region flanked by and .

Ironing Out the Unconventional Mechanisms of Iron Acquisition and Gene Regulation in .

The obligate intracellular pathogen , along with its close species relatives, is known to be strictly dependent upon the availability of iron. Deprivation of iron induces an aberrant morphological phenotype termed "persistence." This persistent phenotype develops in response to various immunological and nutritional insults and may contribute to the development of sub-acute -associated chronic diseases in susceptible populations.