1-Aminocyclopropane-1-Carboxylate and Its Chemoreceptor Drive Metabolic Reprogramming to Enhance Chemotactic Rhizocompetence in Pseudomonas sp. UW4

Biotechnological potential of Paenarthrobacter nicotinovorans ATCC 49919 for the microbial conversion of nicotine and tobacco extracts into 6-hydroxynicotine

Although not achieving near-stoichiometric yields reported for knockout-based systems, the described platform offers a controllable and feedstock-flexible approach for nicotine waste valorization.

The bacterial quorum-sensing molecule 2’-aminoacetophenone reprograms macrophage metabolism and sustains histone lactylation for persistence 2253661

Pseudomonas aeruginosa (PA) uses its quorum-sensing molecule 2’-aminoacetophenone (2-AA) to modulate host mitochondrial activity. This study investigates how 2-AA—driven host metabolic reprogramming contributes to macrophage dysfunction and supports bacterial persistence. We used biochemical and molecular assays to show that 2-AA induced host lactate augmentation. Immunoprecipitation identified proteins involved in histone lactylation (Kla), while CUT&RUN and transcriptomics studies deciphered gene regulation and molecular anergy. Mechanistically, 2-AA disrupts the ESRRA—PPARGC1α regulatory axis, leading to the downregulation of the mitochondrial pyruvate carrier (MPC1). This impairment affects pyruvate transport into mitochondria, rewiring cellular metabolism to a glycolytic state, leading to increased lactate dehydrogenase A (LDHA) activity, elevated and sustained lactate levels in PA-infected immune cells and host tissues, and Kla. Genome-wide profiling of H3 lysine 18 lactylation (H3K18la) demonstrated distinct chromatin modification at regulatory regions, indicating novel epigenetic regulation by lactylation. The 2-AA-mediated H3K18la involves the GTP-specific succinyl-CoA synthetase (GTPSCS) and its interaction with histone lactyl-transferases CREB-binding protein (CBP) and p300. In agreement with H3k18la signatures, transcriptomic profiling of wild-type PA and its 2-AA-deficient mutant revealed regulatory pathways modulating immune and metabolic responses. Functionally, enhanced H3K18la favors a tolerogenic macrophage phenotype that supports intracellular bacterial survival. Conversely, inhibiting lactate accumulation or blocking 2-AA synthesis diminishes H3K18la and enhances bacterial clearance. Collectively, these findings uncover a previously unrecognized QS-regulated metabolic—epigenetic axis through which PA manipulates host immunity, highlighting lactate metabolism as a potential therapeutic target for combating chronic Pseudomonas infections. N/A Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)

In vitro metabolic signaling in two intestinal bacterial isolates: glutamate-driven transcriptional and functional reprogramming in Clostridium butyricum and Bacteroides thetaiotaomicron

ABSTRACT Monosodium glutamate (MSG; L-glutamate monosodium salt) is among the most widely used flavor enhancers, yet its molecular effects on gut microbial physiology remain poorly understood. Here, we examined the strain-specific transcriptomic and metabolic responses of Clostridium butyricum and Bacteroides thetaiotaomicron grown in pure anaerobic culture with 0.1% (wt/vol) MSG. Although MSG exposure was not associated with major changes in total bacterial biomass dynamics, both species showed a temporal functional reprogramming. In C. butyricum, MSG rapidly intensified metabolic activity to capitalize on exogenous glutamate by activating central carbon metabolism, redox-balancing pathways, and the GABA shunt, thereby collectively enhancing butyrate synthesis, a metabolite associated with gut barrier integrity, energy regulation, and anti-inflammatory signaling. On the other hand, B. thetaiotaomicron adopted a conservative, homeostatic response, suppressing glycan utilization and central carbon and energy metabolism, and maintaining stable SCFA production through controlled regulation that buffered against abrupt dietary perturbations. Overall, MSG functioned as a potent metabolic signal, triggering distinct adaptive strategies in two dominant gut bacteria. IMPORTANCE The impact of monosodium glutamate (MSG) as a highly consumed food additive on the gut microbiome is often overlooked, and community-level analyses reveal little change, masking distinct phenotypic responses of individual strains. By combining gene expression and metabolite profiling using two key human gut bacteria, we show that MSG is sensed as a metabolic signal. A butyrate-producing gut bacterium increases energy metabolism and butyrate production, and a fiber-degrading gut bacterium transiently moderates metabolism to maintain stable fermentation products. These differences suggest that MSG's physiological effects may depend on which bacterial groups dominate an individual’s microbiome. The impact of monosodium glutamate (MSG) as a highly consumed food additive on the gut microbiome is often overlooked, and community-level analyses reveal little change, masking distinct phenotypic responses of individual strains. By combining gene expression and metabolite profiling using two key human gut bacteria, we show that MSG is sensed as a metabolic signal. A butyrate-producing gut bacterium increases energy metabolism and butyrate production, and a fiber-degrading gut bacterium transiently moderates metabolism to maintain stable fermentation products. These differences suggest that MSG's physiological effects may depend on which bacterial groups dominate an individual’s microbiome.

Targeting methyl-accepting chemotaxis transmembrane sensory protein inhibits Helicobacter pylori autoinducer-2 quorum sensing system

Rapid Thiamethoxam Biodegradation by Paenarthrobacter nicotinovorans GY-1: Mechanistic Insights and Nitro-Reductive Pathway Elucidation.

The neonicotinoid insecticide thiamethoxam (THX) poses ecological risks and requires efficient bioremediation strategies. We isolated a highly efficient THX-degrading strain, Paenarthrobacter nicotinovorans GY-1, from contaminated agricultural soil. Under response surface-optimized conditions, GY-1 achieved an unprecedented THX degradation rate of 2.08 mg·L-1·h-1, the highest reported for a microorganism to our knowledge. Transcriptomics, enzyme assays, and carbon-source profiling showed that strain GY-1 suppresses glycolysis and reprograms central metabolism when THX is used as the sole nitrogen source. Q-TOF MS and 1D/2D NMR analyses unequivocally determined the structures of two purified intermediates, THX-1 and THX-2, providing direct structural evidence for nitro-reduction and deimination during THX biodegradation. On the basis of these confirmed intermediates, we proposed a nitro-reductive bacterial transformation pathway. This work reveals a microbial adaptation mechanism and provides a potent biocatalyst for the eco-friendly remediation of THX-contaminated environments.

Systems-level analysis of 1,6-hexanediol stress response and tolerance engineering in Escherichia coli

1,6-Hexanediol (1,6-HDO) is an important chemical platform widely used in polymer and pharmaceutical industries, while its toxicity remains a major bottleneck limiting efficient microbial production. This study demonstrates that 1,6-HDO exhibited strong inhibitory effects on Escherichia coli, reducing the maximum OD600 to approximately 50% of the control level under 10 g/L stress. Transcriptomic analysis was performed under 1,6-HDO stress, identifying 779 differentially expressed genes enriched in pathways related to energy metabolism, sulfur metabolism and amino acid metabolism. To systematically identify functional targets associated with tolerance, genome-wide screening using the ASKA overexpression library identified 93 tolerance-related genes that improved E. coli growth under 1,6-HDO stress by 0.06- to 3.17-fold. Notably, multiple targets were functionally associated with energy and amino acid metabolism, consistent with the transcriptomic analysis. Furthermore, co-expression of rumA and yhbO showed the greatest improvement in growth, reaching a biomass of 9.43 under 1,6-HDO stress, which was 2.61-fold higher than that of the control strain. Collectively, this study systematically elucidates the global stress response and identifies key determinants contributing to tolerance, providing valuable targets for developing robust microbial cell factories for efficient 1,6-HDO bioproduction.