Review: prospects for the use of extracts and polysaccharides from marine algae to prevent and treat the diseases caused by Helicobacter pylori.

Helicobacter pylori possesses a broad spectrum of pathogenic factors that allow it to survive and colonize the gastric mucosa, and thus, the pathogenetic targets, which have the same diversity, require search for and the development of alternative, effective, and innocuous means for the eradication of H. pylori. In recent years, fucoidans have been extensively studied due to the numerous interesting biological activities, including the anti-adhesive, anti-oxidative, antitoxic, immunomodulatory, anticoagulant, and anti-infection effects. This review summarizes the data on the effects of extracts and sulfated polysaccharides of marine algae, mainly fucoidans, on pathogenic targets in Helicobacter infection. The pathogenetic targets for therapeutic agents after H. pylori infection, such as flagellas, urease, and other enzymes, including adhesins, cytotoxin A (VacA), phospholipase, and L-8, are characterized here. The main target for the sulfated polysaccharides of seaweed is cell receptors of the gastric mucosa. This review presents the published data about the pleiotropic anti-inflammatory effects of polysaccharides on the gastric mucosa. It is known that fucoidan and other sulfated polysaccharides from algae have anti-ulcer effects, prevent the adhesion of H. pylori to, and reduce the formation of biofilm. The authors speculate that the effect of sulfated polysaccharides on the infectious process caused by H. pylori is related to their action on innate and adaptive immunity cells, and also anti-oxidant and antitoxic potential. Presented in the review are materials indicated for the study of extracts and sulfated polysaccharides from seaweed during H. pylori infection, as these compounds are characterized by multimodality actions. Based on the analysis of literary materials in recent years, the authors concluded that fucoidan can be attributed to the generation of new candidates to create drugs intended for the inclusion in the scheme of eradication therapy of H. pylori infection.

Fucoidan extracted from Fucus evanescens prevents endotoxin-induced damage in a mouse model of endotoxemia.

An important problem of treating patients with endotoxemia is to find drugs to reduce the negative effects of endotoxin on the organism. We tested fucoidan (sulfated polysaccharide) from the brown alga Fucus evanescens as a potential drug in a mouse model of endotoxemia inducted by lipopolysaccharide (LPS). The survival time of mice injected with LPS increased under fucoidan treatment compared with the group of mice injected with LPS only. The preventive administration of fucoidan to mice with endotoxemia resulted in inhibition of increased levels of proinflammatory cytokines (TNFα and IL-6), as well as decreasing of the processes of hypercoagulability. The parenteral or per os administration of fucoidan resulted in decreasing the degree of microcirculatory disorders and secondary dystrophic-destructive changes in parenchymal organs of mice with endotoxemia. Taken together, these results demonstrate that fucoidan prevents endotoxin-induced damage in a mouse model of endotoxemia and increases the mice's resistance to LPS.

Study of Viral Coinfection of the Ixodes persulcatus Ticks Feeding on Humans in a Natural Focus of the South of the Far East.

The phenomenon of pathogen co-infection detected in a half-fed Ixodes persulcatus tick taken from a human in the south of the Far East was studied. Research was carried out on PEK, Vero, and Vero-E6 cell lines, outbred mice, and chicken embryos using ELISA, PCR, IMFA, plaque formation, and electron microscopy. The tick contained an antigen and a genetic marker of the tick-borne encephalitis virus (TBEV). The patient had post-vaccination antibodies in a titer of 1:200, as a result of which, obviously, an antibody-dependent elimination of TBEV occurred. The tick-borne co-isolate also contained an unknown pathogen (Kiparis-144 virus), which, in our opinion, was a trigger for the activation of chronic infection in suckling white mice. In the laboratory co-isolate, ectromelia virus was present, as evidenced by paw edema during the intradermal infection of mice, characteristic rashes on the chorioallantoic envelope of chicken embryos, and typical plaques on Vero-E6. The Kiparis-144 virus was not pathogenic for white mice and chicken embryos, but it successfully multiplied in the PEK, Vero, and Vero-E6 lines. Viral co-infection was confirmed by electron microscopy. Passaging on mice contributed to an increase in the virulence of the co-isolate, whose titer increased by 10,000 times by the fifth passage, which poses an epidemiological danger.

Far Eastern Scarlet-Like Fever is a Special Clinical and Epidemic Manifestation of Yersinia pseudotuberculosis Infection in Russia.

Pseudotuberculosis in humans until the 1950s was found in different countries of the world as a rare sporadic disease that occurred in the form of acute appendicitis and mesenteric lymphadenitis. In Russia and Japan, the Yersinia pseudotuberculosis (Y. pseudotuberculosis) infection often causes outbreaks of the disease with serious systemic inflammatory symptoms, and this variant of the disease has been known since 1959 as Far Eastern Scarlet-like Fever (FESLF). Russian researchers have proven that the FESLF pathogen is associated with a concrete clonal line of Y. pseudotuberculosis, characterized by a specific plasmid profile (pVM82, pYV 48 MDa), sequence (2ST) and yadA gene allele (1st allele). This review summarized the most important achievements in the study of FESLF since its discovery in the Far East. It has been established that the FESLF causative agent is characterized by a unique phenomenon of psychrophilicity, which consists of its ability to reproduce in the environment with its biologically low and variable temperature (4-12 °C), at which the pathogen multiplies and accumulates while maintaining or increasing its virulence, which ensures the emergence and development of the epidemic process. The key genetic and biochemical mechanisms of Y. pseudotuberculosis adaptation to changing environmental conditions were characterized, and the morphological manifestations of the adaptive variability of these bacteria in different conditions of their habitat were revealed. The main features of the pathogenesis and morphogenesis of FESLF, including those associated with the Y. pseudotuberculosis toxigenicity, were presented. The pathogenetic value of the plasmid PVM82, found only in the FESLF pathogen, was shown.

Toxin-Antitoxin Systems and their Role in Maintaining the Pathogenic Potential of Causative Agents of Sapronoses.

In interepidemic periods, causative agents of sapronoses typically employ a variety of mechanisms for maintaining the viability in terrestrial parasitic systems, associated with different adaptive strategies and utilized by their populations to survive. Unlike spore-forming bacteria, causative agents of sapronoses form resistant cell forms: viable but nonculturable (VBNC) cells and persistence (dormant) cells. The implementation of these strategies is mediated by the influence of various stressors of the environment and is characterized by a decrease in metabolism, a change in the morphology and physiology of the bacterial cell, and also the cessation of its replication. While most of the bacterial population is killed under antibiotic exposure, this fraction of pathogens transiently exhibits a phenotypic multidrug-tolerance, causing relapses and chronic courses of many sapronoses. It is important to note that when these resistant cell forms retain virulence and when favorable conditions occur, they are again transformed into active vegetative forms. For this reason, understanding mechanisms, allowing a fraction of the bacterial population to acquire transiently multidrug-tolerance represents an essential step to eradicate these dormant populations. The discovery of the genetic modules of bacterial toxin-antitoxin systems (TAS) in recent years, was proposed to be an ideal and promising candidate to control these complex regulatory molecular mechanisms. Overexpression of the toxins often increases persister frequency in a defined population. In this review, we summarize the scientific data regarding the TAS modules involved in bacterial persistence to be used as antibiotics for the conservation of the pathogenic potential of resistant forms of pathogens of natural focal sapronosis in interepidemic periods.

Cell geteromorphism in the conditions of persistence of sapronoses causative agents in various environments.

The paper discusses the issues of morphofunctional variability of causative agents of sapronoses under stressful environmental conditions. In the current century, sapronoses infections attract more and more attention. Under unfavorable habitat conditions, their pathogens use a strategy for the formation of resting (stable) states: viable but non-cultured cell forms and the persistence of bacteria, which are characterized by reduced metabolism, changes in the morphology and physiology of microorganisms, and termination of their replication. With the formation of resistant forms of bacteria, the possibility of survival of sapronoses causative agents in the interepidemic period, the formation of their antibiotic resistance, which plays an important role in the chronicity of infections, is associated. The literature widely discusses the mechanisms and conditions for the formation of resistant states of pathogenic bacteria, their pathogenetic significance in infectious pathology, whereas the ultrastructural organization and morphological variability of resistant cellular forms, as well as their differentiation, causing the heterogeneity of the pathogens population, are not yet well covered. The emergence of molecular cell biology methods and the discovery of genetic modules of toxin-antitoxin systems revealed a single mechanism for regulating the formation of resistant cellular forms of bacteria. This served as the basis for the development of fundamentally new technologies for the study of the mechanisms for the conservation of the pathogenic potential of resistant cellular forms of pathogens of natural focal sapronosis in interepidemic periods. Based on the analysis of current data, as well as their own experience, the authors assess the role of morphofunctional changes in resistant cellular forms of bacteria and their significance in the adaptation strategies of causative agents of sapronoses (on the example of Yersinia pseudotuberculosis). The study of the manifestations of heteromorphism of causative agents of sapronoses forms the paradigm of the need to improve methods for detecting resistant forms of these bacteria in human and animal biomaterial in order to diagnose chronic recurrent and persistent infections, create effective strategies for monitoring and monitoring the environment.