Biology subjects

Goh, B.

Publications and source records attributed to Goh, B..

3 recordsLinked to original sources

bioRxiv2025

Bacterial glycosphingolipids orchestrate colonization and immune modulation in neonatal host

Symbiotic microbiota has co-existed with the mammalian host over millennia, conserving a stable community structure generation after generation. During the vertical transmission, gut symbionts rapidly colonize the unoccupied host lumen, nonetheless, how symbionts adapt to the dynamic changes of host environment, and contribute to the structural and immunological maturation remains elusive. Here, we show that the early gut symbiont Bacteroides fragilis produces a species- and stage-specific sphingolipid, alpha-galactosylceramide (BfaGC), that orchestrates neonatal colonization and immune modulation. BfaGC stabilizes membrane integrity and facilitates aerobic respiration, providing a critical advantage under early-life oxygen exposure. Temporally induced in the neonatal gut, BfaGC is necessary to regulate colonic type I natural killer T (NKT) cells, highlighting metabolic adaptation of the symbiont is synchronized with the time-sensitive host development. These findings reveal a mutualistic benefit exerted by endobiotic lipid metabolites in host-microbe interactions and provide new insights into species-specific mechanisms in early microbiota establishment and host immune education.

microbiology↗

bioRxiv2023

Identification of visible and near-infrared signature peaks for arboviruses and Plasmodium

Arbovirus and malaria infections affect more than half of the worlds population causing major financial and physical burden. Current diagnostic tools such as microscopy, molecular and serological techniques are technically demanding, costly, or time consuming. Near-infrared spectroscopy has recently been demonstrated as a potential diagnostic tool for malaria and arbovirus and as a screening tool for disease vectors. However, pathogen specific infrared peaks that allow detection of these infections are yet to be described. In this study, we identified unique NIRS peaks from existing laboratory strains of four major arboviruses including Barmah Forest virus (BFV), Dengue virus (DENV), Ross River virus (RRV), Sindbis virus (SINV) and Plasmodium falciparum. Secondly, to determine the diagnostic ability of these peaks, we developed machine learning algorithms using Artificial Neural network (ANN) to differentiate arboviruses from media in which they are grown. Signature peaks for BFV were identified within the visible region at 410, 430, 562 and 588nm and the NIR region at, 946, 958, 1130, 1154 and 1780 nm. DENV related peaks were seen at 410nm within the visible region and 1130 nm within the NIR region. Signature peaks for RRV were observed within the visible region at 410 and 430 nm and within the NIR region at 1130 and 1780 nm, while SINV had a prominent peak at 410 nm within the visible region. Peaks at 514, 528, 547, 561, 582, and 595nm and peaks at 1388, 1432, 1681, 1700, 1721, 1882, 1905, 2245, 2278, 2300 nm were unique for P. falciparum. NIRS predictive sensitivity defined as the ability to predict an arbovirus as an infection was 90% (n = 20) for BFV, 100% (n =10) for RRV and 97.5% (n= 40) for DENV, while infection specificity defined as the ability to predict media as not-infected was 100% (n= 10). Our findings indicate that spectral signatures obtained by NIRS are potential biomarkers for diagnosis arboviruses and malaria. Author summaryMore than half of the world is at risk of contracting either malaria or arboviral infections. In resource limited settings, timely detection of these infections and the ability to screen thousands of people in a day using affordable tools is key to preventing their spread and unprecedented outbreaks. This emphasizes the need to develop portable, rapid, and easy to use diagnostic and surveillance tools. The near-infrared spectroscopy technique has recently been shown to be a potential tool for the diagnosis and surveillance of both malaria and arboviral infections. However, signature spectral biomarkers for these infections remain to be described. This study has identified several spectral biomarkers for DEN, RRV, BVF, SIN arboviruses and P. falciparum parasites. These biomarkers will assist the future assessment of this technique as a diagnostic and or surveillance tool for these infections in the field.

microbiology↗

bioRxiv2023

Functional and metagenomic level diversities of human gut symbiont-derived glycolipids

Bioactive metabolites produced by symbiotic microbiota causally impact host health and disease, nonetheless, incomplete functional annotation of genes as well as complexities and dynamic nature of microbiota make understanding species-level contribution in production and actions difficult. Alpha-galactosylceramides produced by Bacteroides fragilis (BfaGC) are one of the first modulators of colonic immune development, but biosynthetic pathways and the significance of the single species in the symbiont community still remained elusive. To address these questions at the microbiota level, we have investigated the lipidomic profiles of prominent gut symbionts and the metagenome-level landscape of responsible gene signatures in the human gut. We first elucidated the chemical diversity of sphingolipid biosynthesis pathways of major bacterial species. In addition to commonly shared ceramide backbone synthases showing two distinct intermediates, alpha-galactosyltransferase (agcT), the necessary and sufficient component for BfaGC production and host colonic type I natural killer T (NKT) cell regulation by B. fragilis, was characterized by forward-genetics based targeted metabolomic screenings. Phylogenetic analysis of agcT in human gut symbionts revealed that only a few ceramide producers have agcT and hence can produce aGCs, on the other hand, structurally conserved homologues of agcT are widely distributed among species lacking ceramides. Among them, alpha-glucosyl-diacylglycerol(aGlcDAG)-producing glycosyltransferases with conserved GT4-GT1 domains are one of the most prominent homologs in gut microbiota, represented by Enterococcus bgsB. Of interest, aGlcDAGs produced by bgsB can antagonize BfaGC-mediated activation of NKT cells, showing the opposite, lipid structure-specific actions to regulate host immune responses. Further metagenomic analysis of multiple human cohorts uncovered that the agcT gene signature is almost exclusively contributed by B. fragilis, regardless of age, geographical and health status, where the bgsB signature is contributed by >100 species, of which abundance of individual microbes is highly variable. Our results collectively showcase the diversities of gut microbiota producing biologically relevant metabolites in multiple layers-biosynthetic pathways, host immunomodulatory functions and microbiome-level landscapes in the host.

microbiology↗