RESUMEN
Bacteriophage therapy is considered one of the most promising therapeutic approaches against multi-drug resistant bacterial infections. Infections caused by Staphylococcus aureus are very efficiently controlled with therapeutic bacteriophage cocktails, containing a number of individual phages infecting a majority of known pathogenic S. aureus strains. We assessed the contribution of individual bacteriophages comprising a therapeutic bacteriophage cocktail against S. aureus in order to optimize its composition. Two lytic bacteriophages vB_SauM-515A1 (Myoviridae) and vB_SauP-436A (Podoviridae) were isolated from the commercial therapeutic cocktail produced by Microgen (Russia). Host ranges of the phages were established on the panel of 75 S. aureus strains. Phage vB_SauM-515A1 lysed 85.3% and vB_SauP-436A lysed 68.0% of the strains, however, vB_SauP-436A was active against four strains resistant to vB_SauM-515A1, as well as to the therapeutic cocktail per se. Suboptimal results of the therapeutic cocktail application were due to extremely low vB_SauP-436A1 content in this composition. Optimization of the phage titers led to an increase in overall cocktail efficiency. Thus, one of the effective ways to optimize the phage cocktails design was demonstrated and realized by using bacteriophages of different families and lytic spectra.
Asunto(s)
Bacteriófagos/genética , Myoviridae/genética , Podoviridae/genética , Infecciones Estafilocócicas/virología , Fagos de Staphylococcus/genética , Staphylococcus aureus/virología , Farmacorresistencia Bacteriana Múltiple/genética , Genoma Viral/genética , Especificidad del Huésped/genética , Humanos , Terapia de Fagos/métodos , Federación de RusiaRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMEN
Mycobacterium tuberculosis Beijing B0/W148 is one of the most widely distributed clusters in the Russian Federation and in some countries of the former Soviet Union. Recent studies have improved our understanding of the reasons for the "success" of the cluster but this area remains incompletely studied. Here, we focused on the system omics analysis of the RUS_B0 strain belonging to the Beijing B0/W148 cluster. Completed genome sequence of RUS_B0 (CP020093.1) and a collection of WGS for 394 cluster strains were used to describe the main genetic features of the population. In turn, proteome and transcriptome studies allowed to confirm the genomic data and to identify a number of finds that have not previously been described. Our results demonstrated that expression of the whiB6 which contains cluster-specific polymorphism (a151c) increased almost 40 times in RUS_B0. Additionally, the level of ethA transcripts in RUS_B0 was increased by more than 7 times compared to the H37Rv. Start sites for 10 genes were corrected based on the combination of proteomic and transcriptomic data. Additionally, based on the omics approach, we identified 5 new genes. In summary, our analysis allowed us to summarize the available results and also to obtain fundamentally new data.
Asunto(s)
Proteínas Bacterianas , Regulación Bacteriana de la Expresión Génica , Genoma Bacteriano , Genotipo , Polimorfismo Genético , Proteoma , Proteínas Bacterianas/biosíntesis , Proteínas Bacterianas/genética , Perfilación de la Expresión Génica , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , Proteoma/genética , Proteoma/metabolismo , ProteómicaRESUMEN
The nucleotide sequence of a blaKPC-2-harboring plasmid (pKPCAPSS) from Klebsiella pneumoniae ST273 isolated in Saint Petersburg, Russia, from a patient with history of recent travel to Vietnam is presented. This 127,970-bp plasmid possessed both IncFII and IncR replicons. blaKPC-2 was localized on a hypothetical mobile element. This element was flanked by 38-bp inverted Tn3 repeats and included a Tn3-specific transposase gene, macrolide resistance operon (mphA-mrx-mphR), and a fragment of blaTEM with unique polymorphisms.
Asunto(s)
Antibacterianos/farmacología , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/genética , Plásmidos/genética , beta-Lactamasas/genética , Asia Sudoriental , Farmacorresistencia Bacteriana/efectos de los fármacos , Farmacorresistencia Bacteriana/genética , Humanos , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/aislamiento & purificación , Macrólidos/farmacología , Pruebas de Sensibilidad Microbiana , Operón , Federación de Rusia , Transposasas/genética , VietnamRESUMEN
Spectinomycin remains a useful reserve option for therapy of gonorrhea. The emergence of multidrug-resistant Neisseria gonorrhoeae strains with decreased susceptibility to cefixime and to ceftriaxone makes it the only medicine still effective for treatment of gonorrhea infection in analogous cases. However, adoption of spectinomycin as a routinely used drug of choice was soon followed by reports of spectinomycin resistance. The main molecular mechanism of spectinomycin resistance in N. gonorrhoeae was C1192T substitution in 16S rRNA genes. Here we reported a Thr-24âPro mutation in ribosomal protein S5 (RPS5) found in spectinomycin resistant clinical N. gonorrhoeae strain, which carried no changes in 16S rRNA. In a series of experiments, the transfer of rpsE gene allele encoding the mutant RPS5 to the recipient N. gonorrhoeae strains was analyzed. The relatively high rate of transformation [ca. 10(-5) colony-forming units (CFUs)] indicates the possibility of spread of spectinonycin resistance within gonococcal population due to the horizontal gene transfer (HGT).