Evolution of host-microbe cell adherence by receptor domain shuffling

Stable adherence to epithelial surfaces is required for colonization by diverse host-associated microbes. Successful attachment of pathogenic microbes via surface adhesin molecules is also the first step in many devastating infections. Despite the primacy of epithelial adherence in establishing host-microbe associations, the evolutionary processes that shape this crucial interface remain enigmatic. Carcinoembryonic antigen associated cell adhesion molecules (CEACAMs) encompass a multifunctional family of vertebrate cell surface proteins which are recurrent targets of bacterial surface adhesins at epithelial surfaces. Here we show that multiple members of the primate CEACAM family exhibit evidence of repeated natural selection at protein surfaces targeted by bacteria, consistent with pathogen-driven evolution. Inter-species diversity of CEACAM proteins, between even closely-related great apes, determines molecular interactions with a range of bacterial adhesins. Phylogenetic analyses reveal that repeated gene conversion of CEACAM extracellular domains during primate divergence plays a key role in limiting bacterial adhesin tropism. Moreover, we demonstrate that gene conversion has continued to shape CEACAM diversity within human populations, with abundant CEACAM1 variants mediating evasion of adhesins from Neisseria gonorrhoeae, the causative agent of gonorrhea. Together this work reveals a mechanism by which gene conversion shapes first contact between microbes and animal hosts.

Selection of production and control strains of Bordetella bronchiseptica for the production of a vaccine against porcine bordetelliosis

Respiratory diseases of pigs are widespread in all countries of the world with developed pig farming and cause significant economic damage to the industry. Bordetelliosis (atrophic rhinitis) is an infectious disease of pigs characterized by partial or complete atrophy of the nasal septum bones, curvature or shortening of the nose, nasal discharge and bleeding, sneezing, and stunting. Against the background of the development and spread of antibiotic resistance, one of the most effective ways to combat this disease is specific prevention. However, domestic vaccines against swine atrophic rhinitis have not been developed. In view of this, the purpose of our work is to study the properties of field isolates of Bordetella bronchiseptica and select production and control strains suitable for the manufacture and control of the effectiveness of vaccines against atrophic rhinitis. To achieve this goal, 15 strains of B. bronchiseptica were isolated using bacteriological methods from various livestock enterprises in Russia. All strains had typical cultural, morphological, tinctorial and biochemical properties. When studying the pathogenicity of field isolates, the method of intraperitoneal infection of white mice at a dose of 1,5×109 microbe cell was used.it was found that only 3 strains out of 15 studied cultures have pathogenicity: № 134-VIEV, 144-VIEV and 194-VIEV. The remaining strains did not cause the death of experimental mice even with a twofold increase in the infecting dose to 3,0×109 microbe cell when determining the virulence of these cultures, expressed in the LD50 index, it was found that the LD50 of strain № 134-VIEV is 4,6×107 microbe cell, № 144-VIEV – 2,9×108 microbe cell, № 194-VIEV – 7,1×107 microbe cell, respectively. The selected strains were used in further studies as the most promising, since the severity of virulence factors should contribute to the high immunogenic activity of the drug. In the course of determining the antigenic properties of strains (in RA), it was found that after the first vaccination of animals, the antibody titer is at the level of 1:153,6±57,24 – 1:204,8±70,10, the second vaccination increased the antibody titer by 4–4,5 times – from 1:614,4±228,93 to 1: 921,6±228,97, respectively. When determining cross-antigenic activity, it was assumed that all three strains have at least one common antigenic determinant, and at least one heterologous one. The severity of cross-antigenic activity was further confirmed during the evaluation of the immunogenic activity of monovaccins. Thus, the mortality rate of animals in the control, non-vaccinated groups was 100%, while in the groups of vaccinated animals, the survival rate reached 80% or higher. This level of immunogenic protection suggests that the protective level of antibodies in the agglutination reaction for white mice with bordetelliosis should be at least 1:358.4. Analyzing the results of this work, we can conclude that specific prevention of pig bordetelliosis can be effective due to careful selection of production strains of the pathogen.