CC BY
23
Vestnik FEB RAS. 2018. № 6 Supplement
UDC 577.114.5:579.841.11:543.422.23 DOI: 10.25808/08697698.2018.202.6S.053
M.S. KOKOULIN, AS. KUZMICH, E.V. SOKOLOVA, A.I. KALINOVSKY, LA. ROMANENKO
Sulfated lipopolysaccharides from marine gram-negative bacteria: structure and biological activity
Key words: lipopolysaccharide, O-polysaccharide, marine bacteria; biological activity
Gram-negative bacteria are an important component of marine ecosystems where they occupy diverse habitats including deep-sea and hydrothermal vents, sea ice as well as open and coastal water areas. Lipopolysaccharides (LPS) are the major component of the outer membrane of gram-negative bacteria. These characteristic and vital molecules maintain the contact between the bacterial cell and the surrounding environment; therefore, it is plausible that many of the functional changes induced by the harsh habitats can target LPS structure. One of the major interests to study marine gram-negative bacteria is their ability to produce biologically active compounds, such as antibiotics, toxins, endotoxins (LPS), anti-tumor and antibacterial agents having pharmacological and biotechnological potential.
In the last few years, we have studied the O-polysaccharides (OPS) and lipids A of LPS from some marine gram-negative bacteria that belong to genera Cobetia, Idiomarina and Poseidonocella. The chemical structure of the carbohydrate moiety of LPS of these marine gram-negative bacteria is diverse and includes rare monosaccharides and non-carbohydrate substituents. Several new sulfated polysaccharides were found.
In detail, bacteria of genus Cobetia (C. pacifica KMM 3789T and KMM 3878) produce sulfated OPS composed of trisaccharide repeating units. The type strain contains D-glucose 3-sul-fate and D-galactose 3-sulfate. A distinctive feature of the OPS of KMM 3878 is the presence of D-galactose 2,3-disulfate. The OPS of marine bacterium C. litoralis KMM 3880T consists of trisaccharide repeating units and includes 2-keto-3-deoxy-D-manno-octanoic acid 5-sulfate. The same sugar residue was found in the disacharide repeating unit of OPS from Poseidonocella pacifica KMM 9010T. Besides eight-carbon sugar, this polysaccharide includes D-rhamnose 2-sulfate. The OPS of another bacterium of genus Poseidonocella - P. sedimentorum KMM 9023T, also consists of disacharide repeating units and contains 2-keto-3-deoxy-D-glycero-D-galacto-nononic and D-glucoronic acid 2-sulfate. One more sulfated OPS was found in the LPS of deep-sea marine bacterium I. abyssalis KMM 227T. It consists of pentasaccharide repeating units and includes 3-(4-hydroxybutyramido)-3,6-dideoxy-D-glucose 2-sulfate.
* KOKOULIN Maxim Sergeevich - PhD, Junior Researcher, KUZMICH Alexandra Sergeevna - Junior Researcher, SOKOLOVA Ekaterina Vladimirovna - PhD, Researcher, KALINOVSKY Anatoly Ivanovich - DSc, Leading Researcher, ROMANENKO Lyudmila Alexandrovna - DSc, Leading Researcher (G.B. Elyakov Pacific Institute of Bioorganic Chemistry, FEB RAS, Vladivostok, Russia). E-mail: [email protected]
The study was partially supported by the grants of the FEBRAS «Far East» project No 18-4-036 and RFBR project No 18-004-00618.
The LPS of bacteria of genus Cobetia were shown to exhibit a heterogenous lipids A, with hexa-, penta- and tetra-acylated species. Two penta-acylated lipid A species have been detected, differing in the acylation pattern. One lipid A form was found to be decorated by four (R)-12:0 (3-OH) and one 12:0 acyl moieties, whereas the other was decorated by three (R)-12:0 (3-OH), one 10:0 and one 12:0.
From biological point of view, we demonstrated that the LPS and O-deacylated LPS from C. litoralis KMM 3880T, C. pacifica KMM 3789T and KMM 3878, P. pacifica KMM 9010T and P sedimentorum KMM 9023T inhibit colony formation of different human cancer cell lines, including melanoma SK-MEL-5 and SK-MEL-28, colorectal carcinoma HT-29 and HCT-116 and breast adenocarcinoma MCF-7. We showed that sulfated OPS retain anticancer properties that open up new prospects for studying the antitumor activity of sulfated LPS and OPS from marine gram-negative bacteria. In addition, the immunological studies demonstrated the very weak capability of marine Gram-negative bacteria LPS to elicit an immune response, as shown by the significantly lower release of pro-inflammatory cytokines in murine and human model systems compared to the potent immunostimulant E. coli LPS.
