RESUMO
Optochin-resistant pneumococci can be rarely caught in clinical microbiology laboratories because of the routine identification of all such strains as viridans group non-pneumococci. We were lucky to find four non-typeable Streptococcus pneumoniae clones demonstrating the different susceptibilities to optochin: one of them (Spn_13856) was resistant to optochin, while the other three (Spn_1719, Spn_27, and Spn_2298) were susceptible. Whole genome nucleotide sequences of these strains were compared to reveal the differences between the optochin-resistant and optochin-susceptible strains. Two adjacent genes coding maltose O-acetyltransferase and uridine phosphorylase which were presented in the genomes of all optochin-susceptible strains and missed in the optochin-resistant strain were revealed. Non-synonymous substitutions in 14 protein-coding genes were discovered, including the Ala49Ser mutation in the C-subunit of the F0 part of the ATP synthase rotor usually associated with pneumococcal optochin resistance. Modeling of a process of optochin interaction with the F0 part of the ATP synthase rotor indicates that the complex of optochin with "domain C" composed by wild-type C-subunits is more stable than the same complex composed of Ala49Ser mutant C-subunits.
Assuntos
Anti-Infecciosos/farmacologia , Farmacorresistência Bacteriana , Genoma Bacteriano , Genômica , Quinina/análogos & derivados , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/genética , Humanos , Testes de Sensibilidade Microbiana , ATPases Mitocondriais Próton-Translocadoras/química , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Simulação de Dinâmica Molecular , Mutação de Sentido Incorreto , Infecções Pneumocócicas/microbiologia , Ligação Proteica , Quinina/farmacologia , Análise de Sequência de DNA , Streptococcus pneumoniae/isolamento & purificaçãoRESUMO
Here we present the first metagenomic study of gut microbiota in patients with alcohol dependence syndrome (ADS) performed in the whole-genome ("shotgun") format. Taxonomic analysis highlighted changes in community "drivers" abundance previously associated with inflammatory processes (including increase in Ruminococcus gnavus and torques, as well as decrease in Faecalibacterium and Akkermansia). Microbiota of alcoholics manifested presence of specific opportunistic pathogens rarely detected in healthy control subjects of the world. Differential analysis of metabolic potential basing on changes in KEGG Orthology groups abundance revealed increase in pathways associated with response to oxidative stress. Analysis of two specific gene groups--alcohol metabolism and virulence factors--also showed increase in comparison with the control groups. We suggest that gut microbiota distinct in alcoholics by both taxonomic and functional composition plays role in modulating the effect of alcohol on host organism.