Biology subjects

Ngo, H. G.

Publications and source records attributed to Ngo, H. G..

3 recordsLinked to original sources

bioRxiv2026

Glycerol-Driven Energy and Proteostasis Underpin Antibiotic Tolerance in Escherichia coli

Bacterial persisters are frequently described as metabolically dormant, yet the endogenous metabolic programs that sustain survival during prolonged nutrient limitation remain poorly understood. Here, using stationary-phase Escherichia coli as a model of antibiotic tolerance, we combine proteomics, genetics, metabolic phenotyping, and single-cell imaging to define a metabolic framework underlying persistence. Perturbation of tricarboxylic acid cycle function broadly reprogrammed stationary-phase physiology, suppressing lipid and glycerol metabolism, altering energy homeostasis and proteostasis, and reducing antibiotic tolerance. Systems-level analyses identified phospholipid-derived glycerol catabolism as a central metabolic node linking endogenous carbon recycling to persistence. Genetic disruption of glycerol utilization impaired proton motive force homeostasis, reduced formation of large polar protein aggregates, altered division-associated remodeling, and sensitized cells to antibiotic-induced lysis. Functional metabolic assays further revealed that persisters retain a selective capacity to utilize glycerol for rapid proton motive force restoration without growth resumption. Together, our findings support a model in which stationary-phase persisters are not metabolically inert but sustained through endogenous metabolic rewiring that coordinates energy maintenance, proteostasis, and antibiotic tolerance.

microbiology↗

bioRxiv2025

The Role of c-Jun Signaling in Cytidine Analog-Induced Cell Death in Melanoma

Melanoma stands as an increasingly pressing health concern. Enhanced mitochondrial metabolism has been reported in melanoma cells that survived treatment with traditional therapeutics, including cytidine analogs like gemcitabine (GEM). These findings suggest that chemotherapeutic drugs may play dual roles in promoting both cell survival and cell death, although the underlying mechanisms require further investigation. Herein, we conducted proteomics analysis on GEM-treated melanoma cells and found a drug-induced activation of DNA damage response and apoptosis, along with cell cycle arrest. Additionally, GEM treatment significantly altered protein networks related to mitochondrial ribosomal activity, the electron transport chain, and translation. Furthermore, we reported an upregulation of the JNK/c-Jun network in connection with the apoptotic proteins. Co-treatment with a Jun N-terminal Kinase (JNK) inhibitor, JNK-IN-8 (JNKi), significantly increased cell survival, suggesting the involvement of c-Jun signaling in GEM-induced cell death. Additionally, proteomics analysis revealed that JNKi downregulated apoptosis in co-treated cells, highlighting the potential role of the JNK/c-Jun network inhibition in chemotherapeutic tolerance. Collectively, our findings bridge gaps in understanding how melanoma cells respond to cytidine analogs by demonstrating the multifaceted effects of these agents in 1) inducing JNK-mediated apoptotic cell death, and 2) promoting a state of cell cycle inhibition.

cancer biology↗

bioRxiv2024

Unraveling CRP/cAMP-Mediated Metabolic Regulation In Escherichia coli Persister Cells

A substantial gap persists in our comprehension of how bacterial metabolism undergoes rewiring during the transition to a persistent state. Also, it remains unclear which metabolic mechanisms become indispensable for persister cell survival. To address these questions, we directed our efforts towards persister cells in Escherichia coli that emerge during the late stationary phase. These cells have been recognized for their exceptional resilience and are commonly believed to be in a dormant state. Our results indicate that the global metabolic regulator Crp/cAMP redirects the metabolism of these antibiotic-tolerant cells from anabolism to oxidative phosphorylation. Although our data demonstrates that persisters exhibit a reduced metabolic rate compared to rapidly growing exponential-phase cells, their survival still relies on energy metabolism. Extensive genomic-level analyses of metabolomics, proteomics, and single-gene deletions consistently highlight the critical role of energy metabolism, specifically the tricarboxylic acid (TCA) cycle, electron transport chain (ETC), and ATP synthase, in sustaining persister levels within cell populations. Altogether, this study provides much-needed clarification regarding the role of energy metabolism in antibiotic tolerance and highlights the importance of using a multipronged approach at the genomic level to obtain a broader picture of the metabolic state of persister cells.

microbiology↗