Biology subjects

Teo, Y. Y.

Publications and source records attributed to Teo, Y. Y..

7 recordsLinked to original sources

bioRxiv2025

Comparative genomics of DH5α-inhibiting Escherichia coli isolates from human feces reveals common co-occurrence of bacteriocin genes with virulence factors and antibiotic resistance genes.

The presence of multi-drug-resistant (MDR) bacteria in healthy individuals poses a significant public health concern, as these strains may contribute to or even facilitate the dissemination of antibiotic resistance genes (ARGs) and virulence factors. In this study, we investigated the genomic features of antimicrobial-producing Escherichia coli strains from the gut microbiota of healthy individuals in Singapore. Using a large-scale screening approach, we analyzed 3,107 E. coli isolates from 109 fecal samples for inhibitory activity against E. coli DH5 and performed whole-genome sequencing on 37 representative isolates. Our findings reveal genetically diverse strains, with isolates belonging to five phylogroups (A, B1, B2, D, and F) and 23 unique sequence types (STs). Bacteriocin gene clusters were widespread, with colicins and microcins dominating the profiles. Notably, we identified a hcp-et3-4 gene cluster, encoding an effector linked to Type VI secretion system. Approximately 40% of the sequenced isolates were MDR, with resistance for up to eight antibiotic classes in one strain. Plasmids were the primary vehicles for ARG dissemination, but chromosomal resistance determinants were also detected. Additionally, over 55% of isolates were classified as potential extraintestinal pathogenic E. coli (ExPEC), raising concerns about their potential pathogenicity outside the intestinal tract. Our study highlights the co-occurrence of bacteriocins, ARGs, and virulence genes in gut-residing E. coli, underscoring their potential role in shaping microbial dynamics and antibiotic resistance. While bacteriocin-producing strains show potential as probiotic alternatives, careful assessment of their safety and genetic stability is necessary for therapeutic applications. ImportanceThis study provides genomic insights into the diverse repertoire of potential bacteriocin production in E. coli strains isolated from a cohort of healthy human subjects in Southeast Asia. Our findings suggest that the co-occurrence of bacteriocin genes with multiple antibiotic resistance and virulence genes is a common feature among non-clinical isolates. This genetic linkage could contribute to the increased abundance of multi-drug-resistant and virulent strains within individual hosts. Moreover, this co-occurrence may facilitate the host colonization with strains carrying antibiotic resistance and virulence determinants, potentially also contributing to the dissemination of resistant and pathogenic strains within the local population and beyond.

microbiology↗

bioRxiv2024

THE NEURONAL ARCHITECTURE OF AUTONOMIC DYSREFLEXIA

Autonomic dysreflexia is a life-threatening medical condition characterized by episodes of uncontrolled hypertension that occur in response to sensory stimuli after spinal cord injury (SCI)1-7. The fragmented understanding of the mechanisms underlying autonomic dysreflexia hampers the development of therapeutic strategies to manage this condition, leaving people with SCI at daily risk of heart attack and stroke8-18. Here, we expose the complete de novo neuronal architecture that develops after SCI and causes autonomic dysreflexia. In parallel, we uncover a competing, yet overlapping neuronal architecture activated by epidural electrical stimulation of the spinal cord that safely regulates blood pressure after SCI. The discovery that these adversarial neuronal architectures converge onto a single neuronal subpopulation provided a blueprint for the design of a mechanism-based intervention that reversed autonomic dysreflexia in mice, rats, and humans with SCI. These results establish a path for the effective treatment of autonomic dysreflexia in people with SCI.

neuroscience↗

bioRxiv2022

PanomiR: A systems biology framework for analysis of multi-pathway targeting by miRNAs

Charting microRNA (miRNA) regulation across pathways is central to characterizing their role in disease. Yet, current methods reveal only individual miRNA-pathway interactions. We have developed a systems biology approach, Pathway networks of miRNA Regulation (PanomiR), that overcomes these limitations to identify miRNA targeting of groups of interacting pathways using gene expression. The approach does not depend on statistically significant enrichment of miRNA target genes in individual pathways or significant differentially expressed genes. Rather, it directly captures differential activity of pathways between states, determining their up-or-down regulation while sensitively detecting biologically-meaningful signals. PanomiR analyzes the co-activity of differentially regulated pathways to determine coordinate functional groups and uses these co-activated grouped pathways to uncover miRNAs that target them. Incorporating both experimentally-supported or predicted miRNA-mRNA interactions, PanomiR robustly identifies miRNAs central to the regulation of disease functions. We applied PanomiR to a liver cancer dataset and showed that it can organize liver cancer pathways and their regulating miRNAs into coordinated transcriptional programs, reflecting the pathogenic mechanisms of hepatocellular carcinoma. PanomiR recapitulated known central miRNAs in liver cancer with a biologically meaningful assignment of pathways under their regulation, unbiased by the number of genes targeted by each miRNA. PanomiR is a granular framework for detecting broad-scale multi-pathway programs under miRNA regulation. It is accessible as an open-source R/Bioconductor package: .

systems biology↗

bioRxiv2021

A functional logic for neurotransmitter co-release in the cholinergic forebrain pathway

The forebrain cholinergic system has recently been shown to co-release both acetylcholine and GABA. We have discovered that such co-release by cholinergic inputs to the claustrum differentially affects neurons that project to cortical versus subcortical targets. The resulting changes in neuronal gain toggles network efficiency and discriminability of output between two different projection subcircuits. Our results provide a potential logic for neurotransmitter co-release in cholinergic systems.

neuroscience↗

bioRxiv2021

Whole-genome analysis of antimicrobial-resistant Escherichia coli in human gut microbiota reveals its origin and flexibility in transmitting mcr-1

Multidrug resistant (MDR) Escherichia coli strains that carry extended-spectrum {beta}-lactamases (ESBLs) or colistin resistance gene mcr-1 have been identified in the human gut at an increasing incidence worldwide. In this study, we sampled and characterized MDR Enterobacteriaceae from the gut microbiota of healthy Singaporeans and show that the prevalence of ESBL-producing and mcr-positive Enterobacteriaceae is 26.6% and 7.3%, respectively. Whole-genome sequencing of 37 E. coli isolates identified 25 sequence types and assigned them into six different phylogroups, suggesting that the human intestinal MDR E. coli strains are highly diverse. In addition, we found that E. coli isolates belonging to phylogroup D, B2 and F carry a higher number of virulence genes, whereas isolates of phylogroup A, B1 and E carry fewer virulence factor genes but are frequent carriers of florfenicol resistance gene floR and colistin resistance gene mcr-1. Comparison of the seven mcr-1-positive E. coli isolates revealed that mcr-1 is carried by conjugative plasmids or embedded in composite transposons, which could potentially mobilize mcr-1 to other pathogenic Enterobacteriaceae strains or MDR plasmids. Finally, we found that 12 out of the 37 MDR E. coli isolates in this study show high similarity to ESBL-producing E. coli isolates from raw meats from local markets, suggesting a potential transmission of MDR E. coli from meat products to the human gut microbiota. Our findings show diverse antibiotic resistance and virulence profiles of intestinal E. coli and call for better countermeasures to block the transmission of MDR E. coli via the food chain. ImportanceThe human gut can harbor both antibiotic resistant and virulent E. coli which may subsequently cause infections. In this study, the antibiotic resistance and virulence traits of antibiotic-resistant E. coli isolates from human gut microbiota of healthy subjects were investigated. The isolated E. coli strains carry a diverse range of antibiotic resistance mechanisms and virulence factor genes, are highly diverse to each other, and are likely to originate from raw meat products from the local markets. Of particular concern are seven E. coli isolates which carry colistin resistance gene mcr-1. This gene can be mobilized into other pathogens and MDR plasmids, thereby spreading resistance to the last-resort antibiotic colistin. Our findings also suggest that raw meat could serve as important source to transmit MDR bacteria into the human gut microbiota.

microbiology↗

bioRxiv2019

New insights into malaria susceptibility from the genomes of 17,000 individuals from Africa, Asia, and Oceania

We conducted a genome-wide association study of host resistance to severe Plasmodium falciparum malaria in over 17,000 individuals from 11 malaria-endemic countries, undertaking a wide ranging analysis which identifies five replicable associations with genome-wide levels of evidence. Our findings include a newly implicated variant on chromosome 6 associated with risk of cerebral malaria, and the discovery of an erythroid-specific transcription start site underlying the association in ATP2B4. Previously reported HLA associations cannot be replicated in this dataset. We estimate substantial heritability of severe malaria (h2 ~ 23%), of which around 10% is explained by the currently identified associations. Our dataset will provide a major building block for future research on the genetic determinants of disease in these diverse human populations.

genetics↗

bioRxiv2016

Genomic analysis of Mycobacterium tuberculosis reveals complex etiology of tuberculosis in Vietnam including frequent introduction and transmission of Beijing lineage and positive selection for EsxW Beijing variant

Introduction Introduction Accession codes AUTHOR CONTRIBUTIONS COMPETING FINANCIAL INTERESTS Online Methods References Tuberculosis (TB) is a leading cause of death from infectious disease and the global burden is now higher than at any point in history 1,2 Despite coordinated efforts to control TB transmission, the factors contributing to its successful spread remain poorly understood. Vietnam is identified as one of 30 high burden countries for TB and MDR-TB with an incidence of 137 TB cases per 100,000 individuals in 2015 2 Recent phylogenomic analyses of the causative agent Mycobacterium tuberculosis (Mtb) in other high-prevalence regions have provided insights into the complex processes underlying TB transmission ...

genomics↗