Hyaluronic Acid--an "Old" Molecule with "New" Functions: Biosynthesis and Depolymerization of Hyaluronic Acid in Bacteria and Vertebrate Tissues Including during Carcinogenesis.

Hyaluronic acid is an evolutionarily ancient molecule commonly found in vertebrate tissues and capsules of some bacteria. Here we review modern data regarding structure, properties, and biological functions of hyaluronic acid in mammals and Streptococcus spp. bacteria. Various aspects of biogenesis and degradation of hyaluronic acid are discussed, biosynthesis and degradation metabolic pathways for glycosaminoglycan together with involved enzymes are described, and vertebrate and bacterial hyaluronan synthase genes are characterized. Special attention is given to the mechanisms underlying the biological action of hyaluronic acid as well as the interaction between polysaccharide and various proteins. In addition, all known signaling pathways involving hyaluronic acid are outlined. Impaired hyaluronic acid metabolism, changes in biopolymer molecular weight, hyaluronidase activity, and enzyme isoforms often accompany carcinogenesis. The interaction between cells and hyaluronic acid from extracellular matrix that may be important during malignant change is discussed. An expected role for high molecular weight hyaluronic acid in resistance of naked mole rat to oncologic diseases and the protective role of hyaluronic acid in bacteria are discussed.

[Optimization of Streptococcus equi subsp. zooepidemicus cultivation process--producer of hyaluronic acid].

AIM: Selection of high-mucoid morphotype of Streptococcus equi subsp. zooepidemicus (Streptococcus zooepidemicus) and study of its morphological, physiological, biochemical and technological characteristics for providing increased secretion of hyaluronic acid (HA). MATERIALS AND METHODS: Submerged cultivation was performed in 100 ml glass flasks without baffles or in 1.5 or 10 1 laboratory bioreactors. LB and MRS media were used for cultivation. Mutagenesis was carried out by UV exposure with consequent selection of mucoid phenotype. HA was determined by carbazole method or after exhaustive acid hydrolysis by reaction of N-acetylglucosamine with Morgan-Elson reagent. Total hyaluronidase activity was evaluated by viscosimeter. Determination of cell and capsule size, ability to ferment carbohydrates and other microbiological, physiological and biochemical tests were performed by standard techniques. RESULTS: Instability of capsule phenotype of S. zooepidemicus B-8014 strain was revealed that is explained most probably by formation under certain conditions of bacterial hyaluronidase. This is confirmed by a reduction of HA concentration in cultural medium at pre- and stationary growth phases. Mucoid strain S. zooepidemicus KB-04 was obtained by mutagenesis with subsequent selection that is characterized by increased capsules. The strain was studied for HA formation. Optimization of growth medium composition, physical-chemical conditions and modes of cultivation allowed to significantly increase HA yield. CONCLUSION: The studies of morphologic, physiologic, biochemical and technological characteristics of the high-mucoid S. zooepidemicus KB-04 strain obtained by mutagenesis with consequent selection were performed, conditions of its cultivation and composition of growth mediu by carbon source and content of bivalent metal ions were optimized.

[Synthesis and degradation of hyaluronic acid by bacteria of Streptococcus genus].

Modern data on metabolism of hyaluronic acid by bacteria from Streptococcus genus are presented. Several species of bacteria forming capsule from hyaluronic acid, which is analogous to glycosaminoglycan of vertebrates, are considered. Different aspects of hyaluronic acid synthesis are described: biochemical synthesis pathway, genetic basis, regulation of expression of genes belonging to hyaluronic acid synthesis operon. Biological role and physiologic importance of hyaluronic acid for bacteria, including its role in overcoming immune barrier by pathogenic species, are discussed. Process of depolymerization of hyaluronic acid in presence of hyaluronatlyases secreted by certain streptococci is considered. Characteristic of streptococcal enzyme hyaluronatlyase, its mechanism of catalytic effect, and biological function are presented.