S-layer protein 2 of 'Lactobacillus crispatus' 2029, its structural and immunomodulatory characteristics and roles in protective potential of the whole bacteria against foodborne pathogens

We have previously demonstrated that human vaginal Lactobacillus crispatus 2029 (LC2029) strain is highly adhesive to cervicovaginal epithelial cells, exhibits antagonistic activity against genitourinary pathogens and expresses surface-layer protein (Slp). The aims of the present study were elucidation of Slp structural and immunomodulatory characteristics and its roles in protective properties of the whole vaginal LC2029 bacteria against foodborne pathogens. Enteric Caco-2 and colon HT-29 cell lines were used as the in vitro models of the human intestinal epithelial layer. LC2029 strain has two homologous surface-layer (S-layer) genes, slp1 and slp2. Whilst we found no evidence for the expression of slp1 under the growth conditions used, a very high level of expression of the slp2 gene was detected. C-terminal part of the amino sequence of Slp2 protein was found to be highly similar to that of the conserved C-terminal region of SlpA protein of L. crispatus Zj001 isolated from pig intestines and CbsA protein of L. crispatus JCM5810 isolated from chicken intestines, and was substantially variable at the N-terminal and middle regions. The amino acid sequence identity between SlpA and CbsA was as high as 84%, whilst the identity levels of these sequences with that of Slp2 were only 49% and 50% (respectively). LC2029 strain was found to be both acid and bile tolerant. Survival in simulated gastric and intestinal juices of LC2029 cells unable to produce Slp2 was reduced by 2-3 logs. Vaginal L. crispatus 1385 (LC1385) strain not expressing Slp was also very sensitive to gastric and intestinal stresses. Slp2 was found to be non-covalently bound to the surface of the bacterium, acting as an adhesin and facilitating interaction of LC2029 lactobacilli with the host immature or fully differentiated Caco-2 cells, as well as HT-29 cells. No toxicity to or damage of Caco-2 or HT-29 epithelial cells were detected after 24 h of colonization by LC2029 lactobacilli. Both Slp2 protein and LC2029 cells induced NF-kB activation in Caco-2 and HT-29 cells, but did not induce expression of innate immunity mediators Il-8, Il-1β, and TNF-α. Slp2 and LC2029 inhibited Il-8 production in Caco-2 and HT-29 cells induced by MALP-2 and increased production of anti-inflammatory cytokine Il-6. Slp2 inhibited production of CXCL1 and RANTES by Caco-2 cells during differentiation and maturation process within 15 days. Culturing Caco-2 and HT-29 cells in the presence of Slp2 increased adhesion of bifidobacteria BLI-2780 to these enterocytes. Upon binding to Caco-2 and HT-29 cells, Slp2 protein and LC2029 lactobacilli were recognized by toll-like receptors (TLR) 2/6. It was shown that LC2029 strain is a strong co-aggregator of foodborne pathogens Campylobacter jejuni, Salmonella enteritidis, and Escherichia coli O157:H used in this study. The Slp2 was responsible for the ability of LC2029 to co-aggregate these enteropathogens. Slp2 and intact LC2029 lactobacilli inhibited foodborne pathogen-induced activation of caspase-9 and caspase-3 as apoptotic biomarkers in Caco-2 and HT-29 cells. In addition, Slp2 and Slp2-positive LC2029 strain reduced adhesion of tested pathogenic bacteria to Caco-2 and HT-29 cells. Slp2-positive LC2029 strain but not Slp2 alone provided bactericidal effect on foodborne pathogens. These results suggest a range of mechanisms involved in inhibition of growth, viability, and cell adhesion properties of pathogenic Proteobacteria by the Slp2 producing LC2029, which may be useful in treatment of necrotizing enterocolitis (NEC) in newborns and foodborne infectious diseases in children and adults, increasing the colonization resistance and maintaining the intestinal homeostasis

On the Path to Housing Reform Analysis and Forecast

Slogans and reality The rate of housing construction has accelerated slightly in the four years that have elapsed since the Twenty-seventh CPSU Congress advanced the task of providing virtually every family with a separate apartment or an individual house by the year 2000. However, another slump was seen after the commissioning of housing peaked at 132.4 million square meters in 1988: new housing again declined in 1989. As regards the number of apartments, in 1987 it was only possible to repeat the level of average annual commissioning of 2.26 million in the Sixth Five-Year Plan. But then there was a twofold increase in the commissioning of apartments, whereas now their commissioning increased by only 13 percent compared with the preceding five-year plan. The number of dwellings under construction again declined starting in 1988. At the same time, the waiting list for housing continued to grow; 18 percent of the families have already been on this list for more than ten years. Thus there was no general improvement in housing conditions: we are now farther away from solving the housing problem than we were four years ago.

Personalization of the use of non-steroidal anti-inflammatory drugs for musculoskeletal diseases. Resolution on the results of the Meeting of Experts of December 13, 2017

The personalization of therapy is one of the innovative approaches gaining an increasingly strong foothold in modern medicine, implying an individual approach to each patient, taking into account the individual characteristics of the patient and the specific clinical case. This same standpoint of personified therapy should be used to plan rational analgesic therapy, the most important component of managing patients with the most common and socially significant diseases, with conditions that have a significant impact on the patient’s quality of life and worsen the course of concomitant diseases. The Meeting of Experts of different specialties such as rheumatologists, neurologists, cardiologists and clinical pharmacologists considered the key aspects of the prescription of NSAIDs, the most widely used class of painkillers, including those used for the relief of musculoskeletal pain. It was noted that when choosing NSAIDs, the practitioner should take into account the diagnosis, the planned duration of  analgesic therapy, the intensity of pain, medical history data, the presence of comorbid diseases and risk factors for drug complications. There are different types of NSAIDs, some of which are most useful for urgent acute pain therapy (eg, ketoprofen), while others are most suitable for long-term pain management in chronic diseases (eg, etoricoxib). In any case, the practitioner should take into account the priority of patient safety and pay the utmost attention to the prevention of NSAIDassociated complications, and also keep in mind the duration of the specific drug administration permitted by the patient information leaflet. It was also noted that the launch of a new generic etoricoxib (Kostarox®) expands the possibilities of analgesic therapy for the Russian practitioners