Friend turned foe: A curious case of disrupted endosymbiotic homeostasis promoting the Warburg effect in sepsis.

Sepsis is a grievous health concern with limited understanding of its precise etiology. Although studies on sepsis have implicated the Warburg effect (mitigation of mitochondrial oxidative phosphorylation, as evident from aerobic glycolysis), we propose that an evolutionary perspective might further unravel its etiology. The endosymbiotic theory suggests that evolution of a eukaryotic cell is a consequence of the fruitful association between an archaea (Asgard) and an alphaproteobacterium (Rickettsia). We hypothesize that, during pathological conditions like sepsis, such endosymbiotic homeostasis between the two systems is perturbed. We underscore the fact (supported by in silico homology analyses) that during sepsis, the Asgard component of a cell is promoted to trigger aerobic glycolysis as well as the innate immune response (spearheaded by the TLR pathway), while suppressing the Rickettsia counterpart, thereby promoting the Warburg effect. It might be this discord between the two endosymbiotic partners (Asgard and Rickettsia-derived cellular components) that promotes sepsis.

Revealing the Significance of the Glycan Binding Property of Butea monosperma Seed Lectin for Enhancing the Antibiofilm Activity of Silver Nanoparticles against Uropathogenic Escherichia coli.

The incompetence of conventional antibiotics against bacteria residing in biofilms demands newer therapeutic intervention. In this study, we demonstrated that the interaction between silver nanoparticles (AgNPs) and Butea monosperma seed lectin (BMSL) forms efficient surface-functionalized AgNPs with excellent antibiofilm competency against uropathogenic Escherichia coli (UPEC). The minimum biofilm inhibitory concentration (MBIC) of AgNPs and the BMSL-AgNP conjugate (BAgNP) against UPEC was 75 and 9.37 µM, respectively. The eight-fold reduction in the MBIC of AgNPs was attributed to lectin functionalization. The chemical modification of serine amino acids affects the hemagglutination activity of BMSL but not its interaction with the AgNPs. At the same time, AgNPs surface-functionalized with modified BMSL display poor antibiofilm activity. Molecular docking studies revealed that BMSL binds to galactose with a free energy of -5.72 kcal/mol, whereas the serine residue-modified BMSL showed the lowest free energy values, suggesting incompetence for binding galactose. These results showcase that the sugar binding site of BMSL aids in the adhesion of AgNPs to the biofilm matrix and disturbs the formation of the biofilm, which was confirmed by light microscopy using crystal violet staining. At 37.5 µM, BAgNPs also have the capability to eradicate preformed biofilm. As a proof of concept, UPEC biofilm prevention and eradication were demonstrated on a urinary catheter. A scanning electron microscopy study showed that BAgNPs prevent bacterial colonization and thereby curtail biofilm growth. In addition to antibiofilm activity, BAgNPs exert antibacterial activity at 18.75 µM, which is four-fold lower than the MIC of AgNPs. A mechanistic study revealed that BAgNPs affect the integrity of the bacterial outer membrane and generate an imbalance in the antioxidant defense, which induces cell death. The results highlight that lectin functionalization can be extended to other nanoparticles and different antibiotics to enhance their efficacy against drug-resistant bacteria.

Synthesis, supramolecular organization and thermotropic phase behaviour of N-acyltris(hydroxymethyl)aminomethane.

Herein, we reported the supramolecular organization of N-acyltris(hydroxymethyl)aminomethane (NATM) in the solid state as well as in aqueous solution. Single crystal X-ray diffraction revealed that NATM adopts a fully interdigitized structure. The thermodynamic parameters associated with thermotropic phase behaviour of NATM was determined by differential scanning calorimetry. The molecular packing and phase state of the NATM analyzed by laurdan and prodan fluorescence supports the formation of an interdigitized phase in aqueous solution. The potential application of the self-assembled NATM vesicles was demonstrated through entrapping model drug, Rhodamine B.

Selective deacetylation of zaluzanin D using transformed Escherichia coli cultures.

The use of conventional and unconventional reaction methodology for the hydrolysis of the acetate group in zaluzanin D resulted in hydration of the 11,13 exocyclic bond along with deacetylation. But the microorganism E. coli selectively cleaved the acetate group to yield zaluzanin C.