Flavobacterial exudates disrupt cell cycle progression and metabolism of the diatom Thalassiosira pseudonana.

Phytoplankton and bacteria form the base of marine ecosystems and their interactions drive global biogeochemical cycles. The effects of bacteria and bacteria-produced compounds on diatoms range from synergistic to pathogenic and can affect the physiology and transcriptional patterns of the interacting diatom. Here, we investigate physiological and transcriptional changes in the marine diatom Thalassiosira pseudonana induced by extracellular metabolites of a known antagonistic bacterium Croceibacter atlanticus. Mono-cultures of C. atlanticus released compounds that inhibited diatom cell division and elicited a distinctive morphology of enlarged cells with increased chloroplast content and enlarged nuclei, similar to what was previously observed when the diatom was co-cultured with live bacteria. The extracellular C. atlanticus metabolites induced transcriptional changes in diatom pathways that include recognition and signaling pathways, cell cycle regulation, carbohydrate and amino acid production, as well as cell wall stability. Phenotypic analysis showed a disruption in the diatom cell cycle progression and an increase in both intra- and extracellular carbohydrates in diatom cultures after bacterial exudate treatment. The transcriptional changes and corresponding phenotypes suggest that extracellular bacterial metabolites, produced independently of direct bacterial-diatom interaction, may modulate diatom metabolism in ways that support bacterial growth.

Disruption of Colorectal Cancer Network by Polyphyllins Reveals Pivotal Entities with Implications for Chemoimmunotherapy.

The prevalence of colorectal cancer has increased world-wide with high rates of mortality and morbidity. In the absence of efficacious drugs to treat this neoplasia, there is an imminent need to discover molecules with multifaceted effects. To this end, we opted to study the effect of steroidal saponins such as Polyphyllins. We performed anticancer activity studies with three analogs of Polyphyllins: Polyphyllin D (PD), Polyphyllin II (PII) and Polyphyllin G (PG). Here we show the potent effect of PD, PII (IC50 of 0.5-1 µM) and PG (IC50 of 3 µM) in inhibiting the viability of colorectal adenocarcinoma cells (DLD-1) and colorectal carcinoma cells (HCT116). PD and PII also showed inhibition of cell proliferation and sustained response upon withdrawal of the compounds when assessed by clonogenic assays in both the cell lines. Elucidation of the molecular mode of action revealed impact on the programmed cell death pathway. Additionally, proteomic profiling of DLD-1 revealed pivotal proteins differentially regulated by PD and PII, including a downregulated peroxiredoxin-1 which is considered as one of the novel targets to combat colorectal cancers and an upregulated elongation factor 2 (EF2), one of the key molecules considered as a tumor associated antigen (TAA) in colon cancer. Entities of cell metabolic pathways including downregulation of the key enzyme Phosphoglycerate kinase 1 of the glycolytic pathway was also observed. Importantly, the fold changes per se of the key components has led to the loss of viability of the colorectal cancer cells. We envision that the multifaceted function of PD and PII against the proliferation of colorectal carcinoma cells could have potential for novel treatments such as chemoimmunotherapy for colorectal adenocarcinomas. Future studies to develop these compounds as potent anti-colorectal cancer agents are warranted.

Zebrafish aversive taste co-receptor is expressed in both chemo- and mechanosensory cells and plays a role in lateral line development.

Fishes rely on both chemical and tactile senses to orient themselves to avoid predators, and to detect and taste food. This is likely achieved by highly coordinated reception of signals by mechano- and chemosensory receptors in fish. A small co-receptor from zebrafish, receptor activity modifying protein (RAMP)-like triterpene glycoside receptor (RL-TGR), was previously found to be involved in recognition of triterpene glycosides, a family of naturally occurring compounds that act as chemical defenses in various prey species. However, its localization, function, and how it impacts sensory organ development in vivo is not known. Here we show that RL-TGR is expressed in zebrafish in both i) apical microvilli of the chemosensory cells of taste buds including the epithelium of lips and olfactory epithelium, and ii) mechanosensory cells of neuromasts belonging to the lateral line system. Loss-of-function analyses of RL-TGR resulted in significantly decreased number of neuromasts in the posterior lateral line system and decreased body length, suggesting that RL-TGR is involved in deposition and migration of the neuromasts. Collectively, these results provide the first in vivo genetic evidence of sensory cell-specific expression of this unusual co-receptor and reveal its additional role in the lateral line development in zebrafish.