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Karataev G.I.,Gamaleya Research Center for Epidemiology and Microbiology | Sinyashina L.N.,Gamaleya Research Center for Epidemiology and Microbiology | Medkova A.Y.,Gamaleya Research Center for Epidemiology and Microbiology | Semin E.G.,Gamaleya Research Center for Epidemiology and Microbiology | And 6 more authors.
Russian Journal of Genetics | Year: 2016

Avirulent B. pertussis bacteria containing IS elements in the bvgAS operon were detected during the study of whooping cough patients and bacilli carriers. The present work is devoted to the study of the accumulation dynamics and the mechanisms of generation of persistent forms of the B. pertussis bacteria in lower monkeys as the most adequate model for extrapolation of the experiment results to humans. By means of the real-time PCR method, it was established that the B. pertussis bacteria lived more than three months in the upper respiratory tract after a single intranasal monkey infection; the period was reduced to 14–28 days during repeated infection. An increase in the portion of B. pertussis Bvg mutants in the population to tens of percent from the total number of registered bacteria was registered. The experimental confirmation of the development and accumulation of avirulent B. pertussis Bvg mutants during the development of the infectious process was obtained. Further study of the composition of the B. pertussis persistent bacteria population at different stages of the disease will make it possible to formulate new approaches to the whooping cough diagnostics and prevention and creation of fundamentally new drugs. © 2016, Pleiades Publishing, Inc.

PubMed | Gamaleya Research Center for Epidemiology and Microbiology
Type: Journal Article | Journal: The Journal of antibiotics | Year: 2016

Therapeutic strategies that target bacterial virulence have received considerable attention. The type III secretion system (T3SS) is important for bacterial virulence and represents an attractive therapeutic target. A novel compound with a predicted T3SS inhibitory activity named CL-55 (N-(2,4-difluorophenyl)-4-(3-ethoxy-4-hydroxybenzyl)-5-oxo-5,6-dihydro-4H-[1,3,4]-thiadiazine-2-carboxamide) was previously characterized by low toxicity, high levels of solubility, stability and specific efficiency toward Chlamydia trachomatis in vitro and in vivo. In this study, we describe the action of CL-55 on Salmonella enterica serovar Typhimurium. We found that CL-55 does not affect Salmonella growth in vitro but suppresses Salmonella infection in vivo. The i.p. injection of CL-55 at a dose of 10mgkg(-1) for 4 days significantly (500-fold) decreased the numbers of Salmonella in the spleen and peritoneal lavages and increased the survival rates in susceptible (BALB/c, I/St) and resistant (A/Sn) mice. Twelve days of therapy led to complete eradication of Salmonella in mice. Moreover, no pathogen was found 4-6 weeks post treatment. CL-55 was not carcinogenic or mutagenic, did not increase the level of chromosomal aberrations in bone marrow cells and had low toxicity in mice, rats and rabbits. Pharmacokinetic studies have shown that CL-55 rapidly disappears from systemic blood circulation and is distributed in the organs. Our data demonstrates that CL-55 affects S. enterica serovar Typhimurium in vivo and could be used as a substance in the design of antibacterial inhibitors for pharmaceutical intervention of bacterial virulence for infection.

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