title: The mystery of the fourth clone: comparative genomic analysis of four non-typeable Streptococcus pneumoniae strains with different susceptibilities to optochin.
abstract: 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.
authors.affiliation: Research Institute of Physical-Chemical Medicine, Ministry of Public Health of Russian Federation, 119992, Malaya Pirogovskaya str., 1a, Moscow, Russia. Larisa.Ikryannikova@gmail.com.
authors.forename: L N
authors.initials: LN
authors.lastname: Ikryannikova
authors.affiliation: Research Institute of Physical-Chemical Medicine, Ministry of Public Health of Russian Federation, 119992, Malaya Pirogovskaya str., 1a, Moscow, Russia.
authors.forename: D S
authors.initials: DS
authors.lastname: Ischenko
authors.affiliation: Federal State Budgetary Institute "Scientific Center of Children Health" of RAMS, Moscow, Russia.
authors.forename: G G
authors.initials: GG
authors.lastname: Lominadze
authors.affiliation: Research Institute of Physical-Chemical Medicine, Ministry of Public Health of Russian Federation, 119992, Malaya Pirogovskaya str., 1a, Moscow, Russia.
authors.forename: A V
authors.initials: AV
authors.lastname: Kanygina
authors.affiliation: Research Institute of Physical-Chemical Medicine, Ministry of Public Health of Russian Federation, 119992, Malaya Pirogovskaya str., 1a, Moscow, Russia.
authors.forename: I Y
authors.initials: IY
authors.lastname: Karpova
authors.affiliation: Research Institute of Physical-Chemical Medicine, Ministry of Public Health of Russian Federation, 119992, Malaya Pirogovskaya str., 1a, Moscow, Russia.
authors.forename: E S
authors.initials: ES
authors.lastname: Kostryukova
authors.affiliation: Federal State Budgetary Institute "Scientific Center of Children Health" of RAMS, Moscow, Russia.
authors.forename: N A
authors.initials: NA
authors.lastname: Mayansky
authors.affiliation: Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow, 119121, Russia.
authors.forename: V S
authors.initials: VS
authors.lastname: Skvortsov
authors.affiliation: Research Institute of Physical-Chemical Medicine, Ministry of Public Health of Russian Federation, 119992, Malaya Pirogovskaya str., 1a, Moscow, Russia.
authors.forename: E N
authors.initials: EN
authors.lastname: Ilina
authors.affiliation: Research Institute of Physical-Chemical Medicine, Ministry of Public Health of Russian Federation, 119992, Malaya Pirogovskaya str., 1a, Moscow, Russia.
authors.forename: V M
authors.initials: VM
authors.lastname: Govorun
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D016680:Genome, Bacterial; D023281:Genomics; D006801:Humans; D008826:Microbial Sensitivity Tests; D025261:Mitochondrial Proton-Translocating ATPases / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D020125:Mutation, Missense; D011008:Pneumococcal Infections / Q000382:microbiology; D011485:Protein Binding; D011803:Quinine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017422:Sequence Analysis, DNA; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification
chemical_list: D000890:Anti-Infective Agents; C017303:ethylhydrocupreine; D011803:Quinine; C474451:F1F0-ATP synthase; D025261:Mitochondrial Proton-Translocating ATPases