Biology subjects

Mukundan, N.

Publications and source records attributed to Mukundan, N..

3 recordsLinked to original sources

bioRxiv2026

Thienothiazolocarboxamides: rapidly cidal agents causing catastrophic thiol collapse in Mycobacterium tuberculosis.

Thienothiazolocarboxamides (TTCs) were discovered as a hit in a whole cell screen for new antituberculosis agents. These molecules were rapidly cidal under both replicating and non-replicating conditions and killed Mycobacterium tuberculosis (Mtb) in macrophages. The heterobicyclic core of this scaffold was essential for activity and resistance to these agents was mediated by loss of EthA, a flavin containing monooxygenase also responsible for the bioactivation of ethionamide. EthA-mediated activation of TTCs in whole cells was found to produce mycothiol adducts and RNAseq profiles revealed a mechanism of action identical to the fungal mycotoxins patulin and nidulalin A. EthA oxidizes the sulfur of the thiazole ring to create a relatively stable sulfenic acid that reacts with cellular thiols. This unique, replication-independent, mechanism suggests the possibility that these molecules may contribute significantly to shortening the duration of tuberculosis chemotherapy.

microbiology↗

bioRxiv2025

Native Olympia Oysters in San Francisco Bay: Microbiome and Antimicrobial Resistance Derived Insights Into Restoration

Restoration of Olympia oyster (Ostrea lurida) reefs can deliver ecological and public-health co-benefits. Characterization of the microbiome can provide valuable insights towards reef health but remains underused especially in San Francisco Bay. To overcome this gap, we applied shotgun metagenomics to oyster tissue, water, sediment, and biofilm collected from five San Francisco Bay sites (Loch Lomond, Point San Quentin, Brickyard Park, China Camp, Dunphy Park; Nov 2023) to profile community structure, Vibrio diversity, and antimicrobial-resistance (AMR) potential. Evaluating beta-diversity based on Bray-Curtis dissimilarities, we saw strong clustering by sample type (PERMANOVA R2 = 0.645, p = 0.001) and no significant clustering by location (R2 = 0.068, p = 0.937). Alpha diversity (Shannon) differed by matrix (Kruskal-Wallis p = 0.000416), with sediment and water highest and oyster tissues lowest. Vibrio taxa occurred at low relative abundance across matrices but were slightly enriched in biofilms and tissues; several Vibrio phages were also detected, consistent with potential (but unconfirmed) top-down control. Resistome profiling revealed a long-tailed distribution dominated by the tetracycline efflux pump tet(C) (70,049 reads) and APH(3)-Ia (4,498 reads), alongside multidrug efflux components (acrAB/-D, mdtABC/H/F/P, mdfA, MexF/MexW). Biofilms were AMR hotspots, while oyster tissues uniquely harbored Vibrio cholerae varG (Subclass B1 {beta}-lactamase). Collectively, our results indicate that matrix, not geography, structures reef microbiomes, that Vibrio is present but scarce, and that biofilms concentrate AMR potential. We propose a microbiome-integrated monitoring approach that stratifies by matrix, prioritizes biofilm resistome tracking, and targets Vibrio surveillance in oysters to align restoration performance with ecosystem-health safeguards.

genomics↗

bioRxiv2024

Poly (A) Binding Protein 2 is critical for stem-progenitor differentiation during regeneration in the planarian Schmidtea mediterranea.

Post-transcriptional regulation has emerged as a key mechanism to regulate stem cell renewal and differentiation, which is essential for understanding tissue regeneration and homeostasis. Poly(A)-binding proteins are a family of RNA-binding proteins that play a vital role in post-transcriptional regulation by controlling mRNA stability and protein synthesis. The involvement of poly(A) binding proteins in a wide range of cellular functions is increasingly being investigated. In this study, we used the regenerative model organism planarian Schmidtea mediterranea, to demonstrate the critical role of poly(A)-binding protein 2 (PABP2) in regulating neoblast maintenance and differentiation. A deficit in PABP2 blocks the transition of neoblasts towards immediate early progenitors, leading to an enhanced pool of non-committed neoblasts and a decreased progenitor population. This is reflected in variations in the transcriptome profile, providing evidence of downregulation in multiple lineages. Thus, insufficiency of PABP2 resulted in defective formation and organization of tissue leading to abnormal regeneration. Our study reveals the essential role of PABP2 in regulating genes that mediate stem cell commitment to early progenitors during tissue regeneration.

cell biology↗