Vol 34, No 1 (2019)

After synthesis and processing in the nucleus, mature mRNA penetrates through nuclear pores to cytoplasm. mRNP particles are formed in the nucleus and remodeled in cytoplasm, resulting in association with factors required for mRNP proper functions. In the cytoplasmic compartment, mRNP particles can include proteins participating in nuclear interactions, as well as new factors specific for cytoplasmic mRNA–protein interactions. Functions of newly synthesized mRNAs and their cytoplasmic localization are substantially diverse. Cytoskeletal and motor proteins were shown to participate in delivery of mRNP particles to their localization sites. Several families of motor proteins are known in eukaryotes, and functions of all of them were shown to be coordinated in order to compose machinery for cargo delivery to specific cytoplasmic destinations. Adapter proteins, mediators between mRNP particles and motor proteins, are also required to make this transport system functional. Unlike the well-studied system of the cytoskeletal and motor proteins, our knowledge of how mRNP particles bind motor proteins via adapter ones is still sparse.

The antibacterial resistance of healthcare-associated infection (HAI) agents is a major public health problem worldwide. Pseudomonas aeruginosa is one of the main HAI agents, especially in intensive care units (ICUs). The present study focuses on the identification of antibacterial resistance genetic determinants and on determining the structure of mobile genetic elements—novel class 1 integrons of P. aeruginosa. P. aeruginosa strains (n = 105) were collected in the Department of the Moscow Neurosurgery ICU in 2013–2016 from the respiratory system (60.0%), urine (28.6%), surgical wounds (5.7%), blood (2.9%), and cerebrospinal fluid (2.9%). The majority (92.4%) of strains were characterized by a phenotype of multidrug-resistance. Beta-lactamase genes bla_VIM-2-like, which are widely distributed in Russia, were identified in 37.7% of strains. The bla_CTX-M-15 gene was carried by 3.0% of strains that is the first report of such gene identification in P. aeruginosa in Russia. Class 1 integrons were detected in 63.0% of strains, with 36.7% of strains carrying seven types of gene cassette arrays: (bla_VIM-2-like), (aadA6-gcuD), (aacA7-bla_VIM-2-like), (aac(3 ')Ic-cmlA5), (aadA6Δ3::ISPa21e-gcuD), (gcu87-aadB-aphA15d-aadA1a), and (bla_PBL-1-aacA4). The latter three gene cassette arrays are new for class 1 integrons. Identification numbers have been assigned to novel integrons: In1379, In1360, and In1375. New genetic structures were described: the aadA6 gene cassette with inserted ISPa21уe element (In1379); the gsu87 gene cassette coding hypothetical protein which is not represented in the GenBank database (In1360); novel allele of aphA15d gene cassette and the bla_PBL-1 gene cassette coding new, not previously described, beta-lactamase of class A (In1375). Identification of novel genetic structures of antibacterial resistance in P. aeruginosa strains isolated in the course of 3 years indicates the activity of genetic processes associated with antibiotic resistance in hospital pathogens in the Department of Neuro-ICU, which indicates the activity of genetic processes associated with the formation of multiple drug resistance of hospital pathogens.

DNA vaccine cocktail construction is one of the most important strategies for the development of new generation multiantigenic vaccine against toxoplasmosis. In the present study DNA cocktail vaccines containing SAG1 and SAG3 (from a native Iranian parasite, AN: JF312642) genes were constructed and their immune response and protective efficacy was evaluated in comparison with control groups in BALB/c mice. For this purpose, the plasmids containing complete SAG3, SAG1 genes were constructed and then the recombinant plasmids were administered via intramuscular injections according to immunized mice three times with three-week intervals. Both alum and MMT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) were used as an adjuvant to enhance the immune response. Both humeral and cellular immune response of the mice groups were evaluation. Finally, the mice in immunized and non-immunized groups were inoculated by the parasite and the mortality of the mice was evaluated on a daily basis. In cytokine assay, the INFγ were found higher in the mice that received the cocktail DNA containing recombinant plasmids. Evaluation of proliferation of splenocytes using the Alum and nano adjuvant MMT assay indicated induction of cellular response. Measurement of total IgG and the isotypes of IgG1 and IgG2a showed that the cocktail DNA stimulated IgG and IgG2a production in comparison with the control groups (P < 0.05). Furthermore, the survival rate of mice in the groups that received the cocktail DNA was significantly higher than that in the control groups (P < 0.05). Accordingly, administration of the cocktail DNA vaccine led to production of higher levels of IFNγ, confirmed by secretion of IgG2a, and the immune response was shifted toward Th1. Thus, the cocktail DNA containing the recombinant plasmids can be an appropriate candidate for immunization against toxoplasmosis.