Nikita G. Sidorov, Alexey D. Kravchenko, Alexander V. Poddubikov, Vera G. Arzumanian
Pages 1-9 (Rus), 10-17 (Eng)
The number of infections caused by microorganisms that are resistant to antibiotics and synthetic antibacterial drugs is growing fast worldwide. This is one of the most important and urgent problems in health care. The main efforts of researchers around the world are focused on solving this issue. Nitrofurans represent one of the most effective classes of antibacterial drugs. We have synthesized 4 analogues of nifuroxazide – a well known nitrofuran antibiotic – and confirmed their structures by NMR, IR spectroscopy, and mass-spectrometry. All of the obtained compounds were studied for antimicrobial and antifungal activity.
Activity against Escherichia coli, Staphylococcus aureus, Staphylococcus haemolyticus, and Pseudomonas aeruginosa was evaluated by the agar diffusion method. The synthesized compounds suppressed the growth of all the studied bacterial strains except Escherichia coli; the diameter of the inhibition zones ranged from 13.5 to 28 mm depending on the concentration of the tested compound and bacterial strain. One of the compounds studied in this project – the pyridine analogue of nifuroxazide – exceeded the activity of the standard (nifuroxazide) against the Staphylococcus aureus. The inhibitory activity of the synthesized compounds against the Candida albicans and Cryptococcus neoformans yeasts was determined using the microdilution method. The results were assessed according to the indicator color change. None of the studied compounds showed activity against these cultures.
The obtained results confirm that substituted nifuroxazides have significant antimicrobial activity and, therefore, can be considered as promising candidates for developing new antibacterial drugs.
Oleg P. Zhirnov, Tatyana E. Konakova, Darisuren Anhlan, Stephan Ludwig, Elena I. Isaeva
Pages 18-27 (Rus), 28-36 (Eng)
Influenza A virus belongs to a family of enveloped viruses with an RNA genome of negative polarity consisting of 8 RNA segments. The transcription of this RNA genome results in the synthesis of positive-sense mRNAs that translate up to 16 unique viral proteins with the help of splicing and translational shift mechanisms. The 8th NS segment encodes the NS1 protein (27 kDa), which is an active interferon antagonist, and the nuclear export protein NEP (14 kDa) through the standard negative polarity pathway. In addition, an alternative open reading frame for the synthesis of a third viral protein (NSP, negative-strand protein) by means of a direct translation of genome polarity RNA (the so-called positive polarity genome strategy) was identified in the NS segment. Since it is unknown as to whether the NSP protein can be synthesized in the infected organism post viral infection, the generation of spleen leucocytes specific to this protein was studied in mice after two sequential infections with influenza A viruses of H1N1 and H3N2 subtypes. It was found that leucocyte clones specifically recognizing a peptide domain in the central region of the NSP protein (amino acid positions 82-119) were generated in mice infected with influenza A viruses. In silico prediction has shown strong major histocompatibility complex-1 (MHC-I) and MHC-II specific epitopes in this central domain of the NSP. Comparative analysis of the influenza H3N2 viruses circulating in humans during 1968-2018 has shown high NSP variability, which was similar to that shown for the hemagglutinin (HA) and neuraminidase (NA) proteins. The highest variability was found to be in the N- and C-terminal parts of the NSP. These observations suggest that synthesis of the NSP protein occurs in infected animals and further support a bipolar (ambisense) strategy of the RNA genome of human influenza A virus.
Pages 37-42 (Eng)
Fighting against pathogenic bacteria that are resistant to antibiotics has become critical for health care worldwide. More than half a million people die every year from infections caused by drug resistant bacteria. Since bacteria acquire resistance to antibiotics very quickly and the development of new antibiotics is a lengthy process, the search for new approaches to stop the spread of bacterial resistance is extremely important. The spread of antibiotic resistance is accomplished mainly by horizontal gene transfer. Scientists are concentrating their efforts on studying the mechanism of this process in order to find a way to stop or reverse it. In this paper, the author gives a brief review of the recent studies on horizontal gene transfer, particularly on incompatibility-based plasmid curing systems. The author examines new possibilities to use the mechanism of horizontal gene transfer for the developing of novel approaches to fight pathogenic bacteria.