Biology subjects

Gopu, V.

Publications and source records attributed to Gopu, V..

6 recordsLinked to original sources

bioRxiv2026

Bacterial nanotubes extend from a tubeosome organelle to establish an intercellular bridge

Bacterial nanotubes are widespread intercellular membranous bridges mediating molecular exchange among neighboring cells, yet their formation and dynamics remain largely unexplored. By combining live-cell imaging with in situ cryo-electron tomography, we describe nanotube biogenesis in the Gram-positive Bacillus subtilis. Nanotubes form elaborate, highly dynamic networks, with extending nanotubes exhibiting multidirectional movement toward nearby cells, repeatedly scanning their surface. Ultimately, nanotubes penetrate through the recipient cell wall to establish an intercellular bridge. Strikingly, nanotubes emerge within milliseconds from lipid-enriched sites representing a previously unrecognized membranous organelle, termed tubeosome, located in an unusual pseudo-periplasmic space beneath the cell wall. We present evidence that tubeosomes comprise proto-nanotube reservoirs that unfold to project nanotubes. Our study uncovers the tubeosome as a novel bacterial organelle and provides the first real-time visualization of intercellular bridge formation. As connecting nanotubes are found across bacteria, archaea, and eukaryotes, this mechanism may reflect a broadly conserved strategy for cellular communication.

microbiology↗

bioRxiv2025

A family of endonucleases that block nanotube-mediated plasmid dissemination

Small non-conjugative plasmids constitute a substantial portion of the bacterial mobile genome, driving the dissemination of beneficial genes, with their transfer primarily attributed to transformation, transduction, or co-mobilization with conjugative elements1-3. Here we explore an understudied plasmid spread route among bacteria, mediated by intercellular membranous nanotube conduits4. We reveal that, unlike traditional donor-to-recipient delivery, Nanotube-dependent Plasmid exchange (NPex) operates bidirectionally, enabling both plasmid donation and, to a lesser extent, plasmid acquisition. By identifying a Bacillus subtilis natural isolate deficient in NPex, we discovered a prophage-encoded factor, YokF, that blocks plasmid transmission, chiefly acting within the donor cell to inhibit plasmid donation. YokF is a nuclease that localizes to the membrane, where it interacts with a nanotube component to selectively impede plasmid transfer through degradation. Importantly, YokF homologs from various bacterial species were found to exhibit anti-NPex activity. Given their prevalence in Gram-positive bacteria, we propose that YokF homologs represent a conserved family of NPex gatekeepers that restrict plasmid flow within bacterial communities.

microbiology↗

bioRxiv2024

A conjugative plasmid exploits flagella rotation as a cue to facilitate its transfer

Conjugation-mediated DNA delivery is the primary mode for antibiotic resistance spread; yet, molecular mechanisms regulating the process remain largely unexplored. While conjugative plasmids typically rely on solid surfaces to facilitate donor-to-recipient proximity, the pLS20 conjugative plasmid, prevalent among Gram-positive Bacillus spp., uniquely requires fluid environments to motivate its transfer. Here we unveiled that pLS20, carried by B. subtilis, induces adhesin-promoted multicellular clustering, which can accommodate various species, offering a stable platform for DNA delivery in liquid milieu. We further discovered that induction of pLS20 promoters, governing crucial conjugative genes, hinges on the presence of donor cell flagella, the major bacterial motility organelle. Moreover, pLS20 regulatory circuit is strategically integrated into a mechanosensing signal transduction pathway responsive to flagella rotation, harnessing propelled flagella to activate conjugation genes exclusively during the host motile phase. This flagella-conjugation coupling strategy, provides the plasmid with the benefit of disseminating into remote destinations, infiltrating new niches.

microbiology↗

bioRxiv2020

An accurate aging clock developed from the largest dataset of microbial and human gene expression reveals molecular mechanisms of aging

Accurate measurement of the biological markers of the aging process could provide an "aging clock" measuring predicted longevity and allow for the quantification of the effects of specific lifestyle choices on healthy aging. Using modern machine learning techniques, we demonstrate that chronological age can be predicted accurately from (a) the expression level of human genes in capillary blood, and (b) the expression level of microbial genes in stool samples. The latter uses the largest existing metatranscriptomic dataset, stool samples from 90,303 individuals, and is the highest-performing gut microbiome-based aging model reported to date. Our analysis suggests associations between biological age and lifestyle/health factors, e.g., people on a paleo diet or with IBS tend to be biologically older, and people on a vegetarian diet tend to be biologically younger. We delineate the key pathways of systems-level biological decline based on the age-specific features of our model; targeting these mechanisms can aid in development of new anti-aging therapeutic strategies.

systems biology↗

bioRxiv2020

A clinically validated human capillary blood transcriptome test for global systems biology studies

Chronic diseases are the leading cause of morbidity and mortality globally. Yet, the majority of them have unknown etiologies, and genetic contribution is weak. In addition, many of the chronic diseases go through the cycles of relapse and remission, during which the genomic DNA does not change. This strongly suggests that human gene expression is the main driver of chronic disease onset and relapses. To identify the etiology of chronic diseases and develop more effective preventative measures, a comprehensive gene expression analysis of the human body is needed. Blood tissue is easy to access and contains a large number of expressed genes involved in many fundamental aspects of our physiology. We report here the development of a whole blood transcriptome clinical test that is high throughput, automated, inexpensive, and clinically validated. The test requires only 50 microliters of blood from a finger prick, enabling access by diverse populations that have been traditionally under-represented in clinical research. The transcripts in the samples are preserved at the time of collection and can be stored and/or transported at ambient temperatures for up to 28 days. The sample preservative protects integrity, while also inactivating all pathogens (bacteria, fungi, and viruses), enabling safe transportation globally. Given its unique set of usability features and clinical performance, this test should be integrated into longitudinal, population-scale, systems biology studies.

systems biology↗

bioRxiv2019

Gut microbiome activity contributes to individual variation in glycemic response in adults

Limiting post-meal glycemic response is an important factor in reducing the risk of chronic metabolic diseases, and contributes to significant health benefits in people with elevated levels of blood sugar. In this study, we collected gut microbiome activity (i.e., metatranscriptomic) data and measured the glycemic responses of 550 adults who consumed more than 30,000 meals from omnivore or vegetarian/gluten-free diets. We demonstrate that gut microbiome activity makes a statistically significant contribution to individual variation in glycemic response, in addition to anthropometric factors and the nutritional composition of foods. We describe predictive models (multilevel mixed-effects regression and gradient boosting machine) of variation in glycemic response among individuals ingesting the same foods. We introduce functional features aggregated from microbial activity data as candidates for association with mechanisms of glycemic control. In summary, we demonstrate for the first time that metatranscriptomic activity of the gut microbiome is correlated with glycemic response among adults.

systems biology↗