Biology subjects

Yeom, J.

Publications and source records attributed to Yeom, J..

6 recordsLinked to original sources

bioRxiv2026

A Snakemake-based bacterial whole genome comparison pipeline for multi-group clinical isolates

Organisms have continuously evolved in response to environmental conditions. Pathogenic bacteria evolve under host and environmental pressures, reshaping their genomes through insertions, inversions, deletions, and duplications during infection. In clinical settings, phenotypic traits of pathogenic bacteria such as virulence or antimicrobial resistance directly affect disease severity, transmission, and treatment. Conventional genotyping provides insights into genomic relatedness but does not always align with these clinically relevant traits, limiting its utility for phenotype-driven interventions. Here, we develop ABComp (Assembly polishing and Bacterial whole-genome Comparison for multi-group clinical isolates), a modular and Snakemake-based workflow for phenotype-driven comparative genomics. ABComp automates assembly polishing, group-wise pangenome analysis, and enables flexible pathogenic marker discovery through user-defined comparisons. We validated ABComp using a Klebsiella pneumoniae ground truth dataset stratified by yersiniabactin presence and successfully recovered the entire locus as a group-specific core marker. By applying ABComp to another dataset of clinical isolates with experimentally measured virulence, we discovered the ferric citrate (Fec) uptake system as a potential marker specific to a hypervirulent group. These results demonstrate ABComps utility in uncovering phenotype-linked genomic markers with clinical significance, supporting targeted treatments and rapid diagnosis.

bioinformatics↗

bioRxiv2026

IscR-mediated morphological regulation confers virulence and stress resistance by reducing stress molecule uptake in Acinetobacter baumannii

Living organisms must adequately respond to stress to survive and proliferate. Bacterial pathogens face multiple stressors during infections, including oxidative stress from host innate immune cells and antibiotic treatment from clinical therapy. The pathogenic bacterium Acinetobacter baumannii is considered the most critical threat to public health due to its broad antibiotic resistance. However, it is poorly known how A. baumannii properly responds to antibiotics and stress molecules during infection. Here, we investigate the mechanisms by which A. baumannii regulates its morphology to reduce the uptake of stress molecules under oxidative stress and antibiotic exposure, thereby conferring virulence and survival during infection. The transcriptional regulator IscR responds to oxidative stress by upregulating pbp1a, which encodes an enzyme involved in peptidoglycan biosynthesis. Under oxidative stress, bacteria undergo a morphological shift from a rod to a coccoid form, reducing their surface area and thus decreasing their absorption of reactive oxygen species. Inactivation of either iscR or pbp1a results in an elongated morphology characterized by an elevated surface area, thereby reducing A. baumannii survival under oxidative stress. Furthermore, IscR-mediated morphological control is essential for survival under antibiotic treatment. Moreover, IscR-mediated morphology regulation is required for A. baumannii survival in macrophage and mouse models. These findings elucidate a strategy by which A. baumannii uses IscR to adapt to stress through morphological control, facilitating its survival during infections against both immune response and antibiotic therapy. IMPORTNACEAcinetobacter baumannii is a major cause of nosocomial infections. It poses a critical threat due to its extensive antibiotic resistance. This study reveals that the pathogen can change its cellular shape to survive immune system attacks and antibiotic treatment. This change represents a previously unknown survival strategy. A. baumannii transitions to a coccoid morphology under oxidative stress and antibiotic treatment. It does so by activating the peptidoglycan synthesis gene pbp1a through the IscR transcriptional regulator. This rapid morphological adaptation helps A. baumannii evade host defenses and resist antibiotic treatment by reducing uptake of stress molecules. Our findings advance understanding of how pathogens adapt to hostile environments and identify new therapeutic targets. By blocking this shape remodeling ability, it may be possible to render pathogenic bacteria more vulnerable to immune responses and antimicrobial treatments. This offers a promising strategy for combating this multidrug-resistant pathogen.

microbiology↗

bioRxiv2026

Metabolic signals regulate resuscitation speed of antibiotic persister bacteria during infection

All living organisms adjust their metabolism in response to environmental changes. Under unfavorable conditions, organisms enter a state of dormancy by halting metabolism, enabling survival. Dormant bacteria become highly tolerant to antibiotics-a phenomenon called persistence. Here, we demonstrate that selective metabolic reprogramming controls the resuscitation speed of persister after antibiotic exposure. Using multi-omics and in silico modeling, we found that dormant bacteria reprogram metabolic pathways to modulate persister awakening. Accumulation of L-serine and reduction of arginine drive rapid resuscitation. L-serine promotes cysteine biosynthesis and motility while reducing energy metabolism to facilitate rapid resuscitation. In contrast, arginine slows regrowth from dormancy by enhancing ethanol-aldehyde and energy metabolism. L-serine and arginine can, respectively, promote or inhibit the regrowth of antibiotic persister cells in macrophages and mouse models, and regulate the awakening speed of Salmonella, E. coli, and methicillin-resistant Staphylococcus aureus (MRSA). These findings suggest new strategies to target chronic bacterial infections. TeaserL-serine speeds and arginine slows the awakening of antibiotic persisters, revealing targets for chronic infection.

microbiology↗

bioRxiv2026

A sensor of oxidative stress confers virulence via response memory in Acinetobacter baumannii

All living organisms must adapt to environmental stresses to survive. The two-component system (TCS) is a prevalent signal transduction mechanism to alter gene expression in response to stress in bacteria. We report that the PmrB sensor of the PmrA/PmrB TCS senses sublethal oxidative stress and encodes a response memory that promotes virulence in Acinetobacter baumannii. PmrB detects oxidative stress through histidine residues with a nickel (Ni2+) cofactor. Nickel oxidation (Ni2+) induces an allosteric effect by altering PmrB conformation, enabling PmrA activation. Activated PmrA induces antioxidant defense genes, including iron-sulfur cluster repair, ferritin, catalase, and peroxidase. Notably, PmrB remains activated after sublethal oxidative stress is removed, as pathogens encounter in the bloodstream and airways during infection. This response memory enables bacteria to respond strongly to subsequent lethal oxidative stress and antimicrobial peptides. In a murine model, disrupting oxidative sensing reduces virulence. In addition, PmrB-mediated response memory is essential for high virulence in clinically isolated multidrug-resistant A. baumannii. Our findings demonstrate how subinhibitory stress detection enables pathogens to achieve full virulence potential and resist stresses during infection.

microbiology↗

bioRxiv2025

Genetic architecture of the developing forelegs of Drosophila prolongata; an exaggerated weapon and ornament

Extreme secondary sexual traits are some of the most striking phenotypes in nature. Studies on the genetics of these phenotypes have largely focused on within-species functional analyses of signalling pathways. Although useful, these do not provide insight into the evolutionary mechanisms that occur during the evolution of trait exaggeration. Drosophila prolongata offers an exceptional opportunity to explore the evolution of trait exaggeration, as it is the only species in the melanogaster species group with male-specific foreleg size exaggeration under both intra- and intersexual selection. Here, we used sex-specific RNA-seq from fore- and midleg tissues during early development and after initiation of sexually dimorphic growth between these tissues in D. prolongata. We also sampled the same developmental stages in D. carrolli ([~]4MYA divergence) and D. melanogaster ([~]20MYA). Using comparisons of gene expression between sexes, species, tissues, and developmental stages, we found a positive relationship between the number, but not the magnitude of differential expression of sex-biased genes, with the extent of phenotypic dimorphism. One gene with a large effect, grain, caused D. prolongata-like leg size phenotypes in D. melanogaster legs when knocked down. We further found only modest changes to magnitude and direction of expression differences in signalling pathways previously implicated in sexually dimorphic evolution. This suggests that these pathways regulating trait expression and dimorphism but may not be primary drivers of their phenotypic evolution. Significance statementHow sexes evolve distinct forms while developing from a shared genome continues to be incompletely resolved. We explore a sexually dimorphic exaggerated trait, enlarged forelegs in Drosophila prolongata, and compare changes in sex-biased gene expression between tissues and developmental stages in D. prolongata and two closely related species without foreleg exaggeration. We show that major developmental pathways dont appear to change substantially in their direction or magnitude of expression between species. We further show a transcription factor, grain, that when knocked-down, induces D. prolongata leg-like phenotypes in D. melanogaster at low penetrance. Our results suggest that despite large morphological differences and patterns of dimorphism, gene expression changes between the developing tissues may be more modest than previously thought.

evolutionary biology↗

bioRxiv2025

Biomarker Discovery via Integrative Multi-omics for Children exposed to Humidifier Disinfectant

RationaleExposure to humidifier disinfectants has been linked to an array of pulmonary disorders and diminished lung functionality particularly reduced Forced Vital Capacity (FVC). ObjectivesThis investigation sought to identify diagnostic biomarkers for early detection of children at elevated risk of developing chronic respiratory conditions following such exposure. MethodsOur research employed a comprehensive multi-omics strategy analyzing 70 pediatric patients alongside 10 controls, seamlessly integrating clinical assessments with transcriptomics, methylomics, proteomics, and metabolomics data. The analytical framework utilized a sophisticated combination of Non-negative Matrix Factorization (NMF), Multi-Omics Factor Analysis (MOFA), and advanced machine learning algorithms. Measurements and Main ResultsNMF clustering uncovered distinctive protein expression patterns associated with integrin-mediated signaling pathways and immune response mechanisms. Complementarily, MOFA identified latent factors correlating with lung function metrics, highlighting critical molecular pathways involved in integrin cell surface interactions and lipid metabolism regulation. Machine learning-based analysis facilitated the development of a multi-marker panel-comprising IGHV2-70, LysoPC (16:0), and hexadecyl ferulate-which achieved 81.46% accuracy in identifying pulmonary dysfunction cohort. ConclusionsThese findings suggest that alterations in integrin-related signaling networks and dysregulation of lipid metabolism play pivotal roles in mediating the long-term pulmonary consequences of humidifier disinfectant exposure. The proposed multi-marker panel offers significant potential for enhanced risk stratification and timely therapeutic intervention. At a Glance CommentaryO_ST_ABSScientific Knowledge on the SubjectC_ST_ABSExtensive epidemiological evidence has established the causal relationship between humidifier disinfectant exposure and pulmonary dysfunction; however, clinically validated biomarkers for predicting chronic lung disease progression remain limited. Pediatric populations demonstrate unique pathophysiological mechanisms distinct from adults, highlighting the critical necessity for biomarker identification grounded in comprehensive molecular understanding. Despite advances in omics technologies, recent investigations have encountered significant obstacles in achieving deeper mechanistic insights, predominantly attributable to methodological constraints in harmonizing clinical phenotypes with high-dimensional molecular datasets. What This Study Adds to the FieldThis investigation elucidates the fundamental contributions of integrin-mediated signaling cascades and lipid metabolic networks to persistent pulmonary dysfunction following humidifier disinfectant exposure. Our analyses revealed coordinated regulation of integrin signaling pathways and immune response networks through NMF clustering, indicating dynamic temporal evolution of inflammatory responses during chronic disease progression, with temporally distinct molecular signatures identified across discrete observation intervals. Multi-omics factor analysis (MOFA) corroborated integrin pathway dysregulation while additionally uncovering systematic suppression of lipid metabolic processes. Furthermore, machine learning algorithms enabled development of a robust three-component biomarker panel--encompassing IGHV2-70, LysoPC (16:0), and hexadecyl ferulate--demonstrating 81.46% classification accuracy for pulmonary dysfunction phenotypes. Collectively, these findings substantially advance mechanistic understanding of chronic lung injury in vulnerable pediatric cohorts and identify clinically relevant biomarkers with translational potential for risk stratification and therapeutic targeting in clinical practice.

systems biology↗