Lividic acid

Organic acids and their salts are usually the first choice in the bread industry to restrict fungal spoilage, but their efficacy is pH-dependent and spoilage by fungi remains as a common threat. Therefore, this study aimed to evaluate the susceptibility of spoilage fungi of bakery products to acetic, sorbic, and propionic acids at different pH. Penicillium roqueforti, Penicilium paneum, Aspergillus pseudoglaucus, Aspergillus montevidensis and Hyphopichia burtonii strains isolated from spoiled products had their minimum inhibitory concentration (MIC) defined by macrodilution. The concentrations tested were: (i) sorbic acid up to 32 mM; (ii) propionic acid up to 1024 mM and (iii) acetic acid up to 800 mM with pH adjusted in 4.5, 5.0, 5.0 and 6.0 after setting the agent concentration. The lowest MICs for all agents were obtained at pH 4.5, usually doubling with every 0.5 pH increase. P. roqueforti strains isolated from spoiled products were the most resistant to all tested preservatives; while strains of the related species P. paneum, showed similar tolerance to acetic and propionic acids but was double more susceptible to sorbic acid. Strains of A. pseudoglaucus and A. montevidensis were indistinctly susceptible to the preservatives and were the most susceptible species to propionic and acetic acids. H. burtonii strains demonstrated the most variable behaviour in comparison to the other strains being the most susceptible to sorbic acid, were like Aspergillus strains regarding propionic acid, but tolerate well acetic acid. Propionic acid concentrations usually allowed in baked goods are lower than the concentrations required to inhibit the most tolerant isolates tested in this study. The same is true for sorbic acid at higher pH levels. Spoilage species of bakery ware presents a distinct susceptibility profile to the preservatives commonly used in this sector, but the high tolerance observed is a cause of concern.

Malignant tumors exhibit altered metabolism resulting in a highly acidic extracellular microenvironment. Here, we show that cytoplasmic lipid droplet (LD) accumulation, indicative of a lipogenic phenotype, is a cellular adaption to extracellular acidity. LD marker PLIN2 is strongly associated with poor overall survival in breast cancer patients. Acid-induced LD accumulation is triggered by activation of the acid-sensing G-protein-coupled receptor (GPCR) OGR1, which is expressed highly in breast tumors. OGR1 depletion inhibits acid-induced lipid accumulation, while activation by a synthetic agonist triggers LD formation. Inhibition of OGR1 downstream signaling abrogates the lipogenic phenotype, which can be rescued with OGR1 ectopic expression. OGR1-depleted cells show growth inhibition under acidic growth conditions in vitro and tumor formation in vivo. Isotope tracing shows that the source of lipid precursors is primarily autophagy-derived ketogenic amino acids. OGR1-depleted cells are defective in endoplasmic reticulum stress response and autophagy and hence fail to accumulate LDs affecting survival under acidic stress.

Glycoconjugates are major constituents of mammalian cells that are formed via covalent conjugation of carbohydrates to other biomolecules like proteins and lipids and often expressed on the cell surfaces. Among the three major classes of glycoconjugates, proteoglycans and glycoproteins contain glycans linked to the protein backbone via amino acid residues such as Asn for N-linked glycans and Ser/Thr for O-linked glycans. In glycolipids, glycans are linked to a lipid component such as glycerol, polyisoprenyl pyrophosphate, fatty acid ester, or sphingolipid. Recently, glycoconjugates have become better structurally defined and biosynthetically understood, especially those associated with human diseases, and are accessible to new drug, diagnostic, and therapeutic developments. This review describes the status and new advances in the biological study and therapeutic applications of natural and synthetic glycoconjugates, including proteoglycans, glycoproteins, and glycolipids. The scope, limitations, and novel methodologies in the synthesis and clinical development of glycoconjugates including vaccines, glyco-remodeled antibodies, glycan-based adjuvants, glycan-specific receptor-mediated drug delivery platforms, etc., and their future prospectus are discussed.