BCG, muramylpeptides, trained immunity (part II): a low molecular weight alternative to multicomponent bacterial immunostimulants for prevention of respiratory infections during a pandemic

During a pandemic, nonspecific immunoprophylaxis of SARS-CoV-2 infection and other acute respiratory infections (ARI), which can worsen the course of COVID-19, is increasingly in demand in addition to specific immunization. BCG vaccine appears to be one of the candidate immunostimulants in this regard. At the same time, other microbe-derived preparations capable of inducing a state of trained immunity deserve attention. BCG and other bacterial immunostimulatory agents containing a large number of biologically active subunits have long been considered as objects of search for promising pharmacological substances. The review analyzes the linkages between BCG, mycobacterial adjuvants, bacterial lysates, trained immunity, muramylpeptides (MPs) and NOD2 receptors in light of the choice of a low molecular weight alternative to multicomponent bacterial immunostimulants for ARI prevention during the COVID-19 pandemic. The search for key molecules by which bacteria stimulate innate and adaptive immune responses proceeds in a spiral. On different loops of this spiral, MPs have repeatedly reproduced the nonspecific effects of multicomponent bacterial adjuvants, vaccines and immunostimulants. MPs and peptidoglycans containing MPs determine the adjuvant properties of the cell walls of mycobacteria and their peptide-glycolipid fraction (wax D). MPs were able to replace Mycobacterium tuberculosis in complete Freunds adjuvant. MPs determine the NOD2-dependent ability of BCG to induce trained immunity. Probably, MPs provide NOD2-mediated long-term prophylactic action of bacterial lysates. All of the above has prompted revisiting the previously obtained evidence of the efficacy of glucosaminylmuramyl dipeptide (GMDP) as a NOD2 agonist in treatment/prevention of respiratory infections. We speculate here that MPs, in particular GMDP, at rational dosing regimens will be able to reproduce many aspects of the nonspecific effects of BCG and multicomponent bacterial immunostimulants in preventing ARI during the COVID-19 pandemic and in the post-pandemic period.

Glycolipids as Potential Energy Molecules during Starvation in Climbing Perch,Anabas testudineus(Bloch)

Glycolipids are membrane lipids which act as cellular markers and also provide energy for the cells. The present study is an attempt to understand whether glycolipids can act as energy sources during fasting. To achieve this, we selected and subjectedAnabas testudineusto short-term (15 days) and long-term (60 days) laboratory starvation. We estimated glycolipids biochemically using a standard protocol in six different tissues. Results showed a selective decline in glycolipid concentration in certain tissues, and also an increase was observed in some tissues. Short-term fasting led to a decline in glycolipids in tissues such as brain (P<0.05), accessory respiratory organ (P<0.001), pectoral and lateral line muscle. Liver and kidney (P<0.002) reported an increase. Long term starvation also resulted in a decline in tissues such as liver (P<0.001), kidney (P<0.001), brain, and accessory respiratory organ. Muscle tissue,that is, both the pectoral (P<0.002) and lateral line muscle (P<0.05), showed an increase in the glycolipid fraction. This selective decline in glycolipid content of certain tissues suggests a possible utilization of these lipids during starvation and the significant upsurge observed in certain tissues suggests a simultaneous synthesis occurring along the degradation, probably reducing the oxidative stress created by ROS (reactive oxygen species).

Divergent Mechanisms of Interaction of Helicobacter pylori and Campylobacter jejuni with Mucus and Mucins

ABSTRACTHelicobacter pyloriandCampylobacter jejunicolonize the stomach and intestinal mucus, respectively. Using a combination of mucus-secreting cells, purified mucins, and a novel mucin microarray platform, we examined the interactions of these two organisms with mucus and mucins.H. pyloriandC. jejunibound to distinctly different mucins.C. jejunidisplayed a striking tropism for chicken gastrointestinal mucins compared to mucins from other animals and preferentially bound mucins from specific avian intestinal sites (in order of descending preference: the large intestine, proximal small intestine, and cecum).H. pyloribound to a number of animal mucins, including porcine stomach mucin, but with less avidity than that ofC. jejunifor chicken mucin. The strengths of interaction of various wild-type strains ofH. pyloriwith different animal mucins were comparable, even though they did not all express the same adhesins. The production of mucus by HT29-MTX-E12 cells promoted higher levels of infection byC. jejuniandH. pylorithan those for the non-mucus-producing parental cell lines. BothC. jejuniandH. pyloribound to HT29-MTX-E12 mucus, and while both organisms bound to glycosylated epitopes in the glycolipid fraction of the mucus, onlyC. jejunibound to purified mucin. This study highlights the role of mucus in promoting bacterial infection and emphasizes the potential for even closely related bacteria to interact with mucus in different ways to establish successful infections.

Quantitative Changes of the Lipid and Fatty Acid Composition of Leaves of Aleurites montana as a Consequence of Growth under 700 ppm CO2 in the Atmosphere

Leaf lipids of Aleurites plants that were cultivated for 5 months in air containing 700 ppm CO2, were compared to those of control plants cultivated at 350 ppm CO2. The content of ether soluble lipids referred to dry matter is the same in CO2-and control plants. The comparison of lipids analyzed as the pigments chlorophyll and carotenoids, phospholipids and glycolipids shows that the ratio of phospholipids and glycolipids is slightly shifted in favor of phospholipids in CO2-plants. Thus, within the group of phospholipids, phosphatidylglycerol and phosphatidylinositol occur in higher concentrations in CO2-plants. Although the differences in the lipid content appear moderate in CO2-and control plants, it is the saturation degree of fatty acids that differs substantially. The fatty acids of CO2-plants contain according to the higher phospholipid content approx. 5% more saturated fatty acids. Stearic acid is three-fold increased. Whereas in the phospholipid fraction saturated fatty acids comprise one half of all fatty acids, the unsaturated fatty acids make up for 80 to 90% in the glycolipid fraction. In CO2-plants not only in the phospholipid fraction but also in the glycolipid fraction saturated fatty acids occur in a higher portion. This means that not only in the cell membrane of CO2-plants but also in the thylakoid membrane the fluidity is decreased. Also in the wax-fraction long-chained carbonic acids with 20 -26 carbon atoms occur. As the portion of these carbonic acids is twice as high in CO2-plants, it is concluded that a stronger formation of the wax layers exists in CO2-plants. By means of Western blotting and by the use of lipid and carotenoid antisera the binding of lipids onto proteins of photosystem II and photosystem I was analyzed. It is seen that besides the major amount of lipids which build up the thylakoid membrane, some lipids are also bound to membrane peptides. Whereas monogalactolipid is bound to the LHCP-complex peptides, to the OEC1 -peptide and the 43 and 47 kDa chlorophyll binding peptides, the anionic lipids sulfoquinovosyldiglyceride and phosphatidylglycerol and digalactolipid are bound to the core peptides of PS II and PS I. β-carotene and the xanthophylls were found to be bound to the core peptides and β-carotene and violaxanthin were also bound to the light-harvesting pigment complex.

Neutral glycolipids ofSchistosoma mansonias feasible antigens in the detection of schistosomiasis

SUMMARYThe neutral glycolipid fraction from mouse-propagated,Schistosoma mansoniadult worms has been investigated as to its chromatographic and antigenic properties, and whether it fulfills the serodiagnostic antigen requirements of sensitivity and specificity in the detection of schistosomiasis. Serological analyses were performed by thin-layer chromatography immunostaining and ELISA. In the acute-phase form of mouse schistosomiasis, the kinetics of development of neutral glycolipid-specific antibody levels was correlated with the intensity of the initial infection and the response was dominated by IgG, as represented by the subclass IgG1. With the experimental animal helminthiases screened, glycolipid antigenicity fulfilled the fundamental traits for a serodiagnostic reagent. In the chronic-phase form of human schistosomiasis mansoni, neutral glycolipid-specific antibody levels were not correlated with the intensity of infection, as estimated from the faecal content of parasite eggs, whilst the isotypic response was dominated by IgM and IgG, the latter represented primarily by IgG1 and secondarily by IgG3. With other human helminthiases, glycolipid antigenicity was incomplete, in that, the specificity was only partially fulfilled. The reason for this incomplete specificity has been clarified, in part, by the detection of cryptic schistosomiasis infections in the cohorts of African patient sera examined.

The glycoinositol-phospholipids of Phytomonas

The Phytomonas spp. are trypanosomatid parasites of plants. A polar glycolipid fraction of a Phytomonas sp., isolated from the plant Euphorbia characias and grown in culture, was fractionated into four major glycolipid species (Phy 1-4). The glycolipids were analysed by chemical and enzymic modifications, composition and methylation analyses, electrospray mass spectrometry and microsequencing after HNO2 deamination and NaB3H4 reduction. The water-soluble headgroup of the Phy2 glycolipid was also analysed by 1H NMR. All four glycolipids were shown to be glycoinositol-phospholipids (GIPLs) with phosphatidylinositol (PI) moieties containing the fully saturated alkylacylglycerol lipids 1-O-hexadecyl-2-O-palmitoylglycerol and 1-O-hexadecyl-2-O-stearoylglycerol. The structures of the Phy 1-4 GIPLs are: Man alpha 1-2Man alpha 1-6Man alpha 1-4GlcN alpha 1-6PI, Glc alpha 1-2(NH2-CH2CH2-HPO4-)Man alpha 1-2Man alpha 1-6Man alpha 1-4GlcN alpha 1-6PI, [formula: see text] Glc alpha 1-2(NH2CH2CH2-HPO4-)Man alpha 1-2Man alpha 1-6Man alpha 1-4(NH2-CH2CH2-HPO4-)GlcN alpha 1-6PI [formula: see text] and Glc alpha 1-2Glc alpha 1-2(NH2CH2-CH2-HPO4-)Man alpha 1-2Man alpha 1-6Man alpha 1-4(NH2CH2CH2-HPO4-)-GlcN alpha 1-6PI. [formula: see text] The Phytomonas GIPLs represent a novel series of structures. This is the first description of the chemical structure of cell-surface molecules of this plant pathogen. The Phytomonas GIPLs are compared with those of other trypanosomatid parasites and are discussed with respect to trypanosomatid phylogenetic relationships.