Biology subjects

Groisman, E. A.

Publications and source records attributed to Groisman, E. A..

3 recordsLinked to original sources

bioRxiv2026

A conserved peptidase governs glucose homeostasis in Bacteroides

Glucose homeostasis is governed by peptidases across the kingdom of life. Host overconsumption of glucose transforms gut microbial compositions and activities. Here, we identify an IDE-like M16 peptidase in human gut commensal Bacteroides that controls glucose-dependent inhibition of the transcriptional regulator, Cur, which is important for intestinal colonization and host-microbial interactions. This regulatory paradigm is independent of fructose, establishing a specific pathway whereby glucose signaling hinders commensal fitness in the host. We determined that this peptidase cleaves targets of other M16-family peptidases, including insulin, to control carbon metabolism through the oxidative pentose phosphate pathway (OPPP). Furthermore, we show that peptidase activity governs the abundance of glycolytic enzymes to alter Cur activity. These findings establish that the activity of an M16 peptidase mediates changes to global transcription in Bacteroides species when glucose is abundant in the host diet.

microbiology↗

bioRxiv2024

Hierarchical glycolytic pathways control the carbohydrate utilization regulator in human gut Bacteroides

Human dietary choices control the gut microbiome. Industrialized populations consume abundant amounts of glucose and fructose, resulting in microbe-dependent intestinal disorders. Simple sugars inhibit the carbohydrate utilization regulator (Cur), a transcription factor in members of the prominent gut bacterial phylum, Bacteroidetes. Cur controls products necessary for carbohydrate utilization, host immunomodulation, and intestinal colonization. Here, we demonstrate how simple sugars decrease Cur activity in the mammalian gut. Our findings in two Bacteroides species show that ATP-dependent fructose-1,6-bisphosphate (FBP) synthesis is necessary for glucose or fructose to inhibit Cur, but dispensable for growth because of an essential pyrophosphate (PPi)-dependent enzyme. Furthermore, we show that ATP-dependent FBP synthesis is required to regulate Cur in the gut but does not contribute to fitness when cur is absent, indicating PPi is sufficient to drive glycolysis in these bacteria. Our findings reveal how sugar-rich diets inhibit Cur, thereby disrupting Bacteroides fitness and diminishing products that are beneficial to the host.

microbiology↗

bioRxiv2020

Limitation of phosphate assimilation maintains cytoplasmic magnesium homeostasis

Phosphorus (P) is an essential component of several core biological molecules. In bacteria, P is mainly acquired as inorganic orthophosphate (Pi). Once in the cytoplasm, Pi is incorporated into adenosine triphosphate (ATP), which exists primarily as a Mg2+ salt. Notably, whereas P is essential, excess of cytosolic Pi hinders growth. Here we demonstrate that cytotoxic effects of excessive Pi uptake result from its assimilation into ATP and subsequent disruption of Mg2+ dependent processes. We show that Salmonella enterica cells experiencing cytoplasmic Mg2+ starvation restrict Pi uptake, thereby limiting the availability of an ATP precursor. This response prevents excessive ATP synthesis, overproduction of ribosomal RNA, chelation of free cytoplasmic Mg2+ and the destabilization of Mg2+-dependent core processes that ultimately hinder bacterial growth and leads to loss of cellular viability. We demonstrate that, even when cytoplasmic Mg2+ is not limiting, excessive Pi uptake leads to increased ATP synthesis, depletion of free cytoplasmic Mg2+, inhibition of translation and growth. Our results establish that bacteria must restrict Pi uptake to prevent the depletion of cytoplasmic Mg2+. Furthermore, they provide a framework to understand the molecular basis of Pi cytotoxicity and reveal a regulatory logic employed by bacterial cells to control P assimilation. ImportancePhosphorus (P) is essential for life. As the fifth most abundant element in living cells, P is required for the synthesis of an array of biological molecules including (d)NTPs, nucleic acids and membranes. Organisms typically acquire environmental P as inorganic phosphate. While essential for growth and viability, excessive intracellular Pi is toxic for both bacteria and eukaryotes. Using the bacterium Salmonella enterica as a model, we demonstrate that Pi cytotoxicity is manifested following its assimilation into ATP, which acts as a chelating agent for intracellular cations, most notably, Mg2+. These results identify physiological processes disrupted by excessive Pi and elucidate a regulatory logic employed by bacteria to prevent uncontrollable P assimilation.

microbiology↗