Biology subjects

Muthukrishnan, S.

Publications and source records attributed to Muthukrishnan, S..

4 recordsLinked to original sources

bioRxiv2025

Transcriptomic responses of Vibrio campbellii to quorum sensing inhibition and antibiotic stress

Quorum sensing (QS) is a key regulatory system in Vibrio campbellii that modulates virulence and communal behaviours. This study investigated the early transcriptional responses to a quorum sensing inhibitor (QSI) and tetracycline using RNA sequencing (RNA-seq). Following one hour of exposure, 130 and 539 differentially expressed genes (DEGs) were identified under QSI and tetracycline treatments, respectively. Quorum sensing inhibitory activities leading to upregulation of sulfur and porphyrin metabolism genes and downregulation of transporters and QS-related pathways, while tetracycline exposure induced genes related to ribosomal activity, DNA replication, and stress responses. KEGG and GO enrichment analyses revealed distinct pathway regulatory patterns, including in quorum sensing, two-component systems, and biofilm formation. These results highlight the mechanistic distinctions in bacterial response to quorum sensing interference versus antibiotic stress, emphasizing the potential of QSIs as precision anti-virulence agents that modulate pathogenic behaviour while minimizing the selective pressure associated with conventional antibiotics.

microbiology↗

bioRxiv2025

Glassy dynamics in active epithelia emerge from an interplay of mechanochemical feedback and crowding.

Glassy dynamics in dense epithelial cells remain a subject of debate, as theory predicts its emergence only at unrealistically low cellular activity, yet experimental studies have shown glassy dynamics at physiologically active conditions. In this study, we address this paradox by integrating experimental observations in epithelial monolayers with an active vertex model. We demonstrate that while crowding is essential, it is not sufficient for glassy dynamics to emerge. A mechanochemical feedback loop (MCFL-1), mediated by cell shape changes through the contractile actomyosin network is required to drive glass transition in dense epithelial tissues. Such mechanochemical feedback is captured experimentally via a crosstalk between actin-based cell clustering and dynamic heterogeneity, as well as via force induced actin reorganization in epithelial cells. Incorporating MCFL into the vertex model reveals contrasting results from those previously predicted by theories-we show that the MCFL can counteract cell division-induced fluidisation and enable glassy dynamics to emerge through active cell-to-cell communication. Furthermore, our analysis reveal, for the first time, the existence of novel collective mechanochemical oscillations that arise from the crosstalk of MCFL-1 with oscillatory MCFL-2, capturing ERK mediated cell shape changes. Together, we demonstrate that an interplay between crowding and active mechanochemical feedback enables the emergence of glass-like traits and collective biochemical oscillations in epithelial tissues with active cell-to-cell contacts.

biophysics↗

bioRxiv2025

Differential interfacial tension between oncogenic and wild-type populations forms the mechanical basis of tissue-specific oncogenesis in epithelia

Why does the same oncogenic mutation drive tumor formation in some tissues but not in others? While cancer driver mutations are well-documented, their tissue-specific effects remain largely attributed to genetic factors, leaving the biophysical aspects underexplored. Here, we demonstrate that mechanical interactions, specifically interfacial tension between newly transformed and wildtype epithelial cells are critical in determining survival and growth of HRasV12 oncogenic mutants in human mammary and bronchial epithelia, leading to contrasting outcomes in the two tissues. In mammary epithelium, isolated oncogenic cells are extruded-a typical mechanism of defense against cancer in epithelia-while oncogenic groups become spatially confined in a kinetically arrested, jammed state, marked by an actomyosin belt at the interface. In contrast, bronchial epithelium permits persistent spreading of the same oncogenic cells, which form long protrusions regardless of colony size. Furthermore, oncogenic clusters in these two tissues exhibit distinct biophysical properties, including variations in cell shapes, intracellular pressure, cell-cell tension, and cellular motility. Using a cell shape-tension coupled bi-disperse vertex model, we reveal that differences in interfacial tension at mutant-wild-type boundaries dictate whether oncogenic cells are eliminated, restrained, or expanded and that modulating the heterotypic interfacial tension alters mutant cell fate within the epithelium. Together, our findings uncover a mechanical basis for tissue-specific oncogenesis by highlighting how differential cellular mechanics at the oncogenic-host cell interface regulate tumor initiation and progression.

biophysics↗

bioRxiv2019

Horizontal gene transfer of the pirAB genes responsible for Acute Hepatopancreatic Necrosis Disease (AHPND) turns a non-Vibrio strain into an AHPND-positive pathogen

In the past decade, shrimp farms, particularly those established in Asia, Mexico and South America suffered from the outbreak of an emergent penaeid shrimp disease known as Acute Hepatopancreatic Necrosis Disease (AHNPD). The PirA and PirB toxins produced by plasmid pVA1 in Vibrio parahaemolyticus were reported to cause the AHPND pathology. More recent research demonstrated that V. parahaemolyticus is not the only species that can cause AHPND, as other Vibrio species were also found to contain PirAB-containing plasmid. The present study assessed the Horizontal Gene Transfer (HGT) of AHPND that transforms genes (pirA and pirB) from AHPND positive V. parahaemolyticus to non-AHPND and non-vibrio species identified as Algoriphagus sp. strain NBP. The HGT of pirA and pirB genes from the AHPND positive V. parahaemolyticus to Algoriphagus sp. strain NBP was found to occur at different temperatures. The conjugation efficiency rate (n{degrees}) of pirAB from V. parahaemolyticus to Algoriphagus sp. strain NBP at 30{degrees}C and 40{degrees}C showed 80-91% efficiency. Shrimp challenged with the pirA and pirB positive Algoriphagus sp. strain NBP also demonstrated typical pathognomonic AHPND lesions during the histopathologic examination. Author summaryAHPND is a significant threat to the shrimp industry leading to high losses. The results demonstrated that the conjugative transfer of the pirA and pirB positive V. parahaemolyticus (donor strain) to a non-Vibrio and non-pathogenic bacterium (recipient strain), successfully transformed the non-pathogenic bacterium into a disease-causing strain with a disease-causing capability similar to the donor strain. Initially, V. parahaemolyticus that express the PirA and PirB toxins which encoded by a conjugative plasmid cause sloughing and degeneration of shrimp hepatopancreatic.

microbiology↗