21 Recent studies have demonstrated that antibiotic resistance in pathogenic bacteria could be 22 reverted to the drug sensitive phenotype by the treatment with the newly introduced iodine 23 containing nanomolecular complex, FS-1. Antibiotic resistance reversion has been verified as a 24 promising therapeutic approach to combat multidrug resistant infections. The mechanisms of 25 action, however, remain unclear. A collection strain, Escherichia coli ATCC showing 26 an extended spectrum of resistance to beta-lactam and aminoglycoside antibiotics was used in 27 this study as a model organism. The FS-1 treated culture and the negative control variant were 28 sequenced by PacBio RS II System following the SMRTbell 20-kb library preparation protocol.29 Total RNA samples of these strains were sequenced by Ion Torrent. It was shown that the 30 treatment with FS-1 caused a profound gene expression alternation switching the bacterial 31 metabolism to anaerobic respiration, increased anabolism, oxidative/acidic stress response and an 32 inhibition of many nutrient uptake systems. All this leads to an increase in the susceptibility to 33 antibiotics even when FS-1 is removed from the medium. The later fact implies an involvement 34 of epigenetic mechanisms in gene regulation and antibiotic resistance reversion. This hypothesis 35 was investigated by base-call kinetic analysis in PacBio reads and DNA methylation profiling in 36 the sequenced genomes. Several DNA motifs of adenosine and cytosine methylation were 37 identified. While the numbers of methylated sites in chromosomes and plasmids of both 38 genomes, NC and FS, were similar, the distribution of the methylated sites was different. It may 39 explain the observed long lasting effect of the treatment of E. coli with FS-1 on antibiotic 40 susceptibility of this model microorganism.41 Author summary 42 The emergence of multidrug resistant bacteria is a great concern, since the misuse of antibiotics 43 have caused a strong selective pressure for these resistant bacteria and various treatment options 44 are becoming ineffective. Drug induced reversion of antibiotic resistant is considering a 45 promising approach to address this problem. This study was set out to investigate genetic 46 mechanisms of action of a new iodine-containing nano-micelle drug FS-1 that induces antibiotic 47 resistance reversion in bacteria. Escherichia coli ATCC BAA-196 was used as a model of 48 multidrug resistant microorganisms. With this purpose in mind, we have sequenced the genomic 49 DNA and total RNA samples of E. coli cultivated on medium containing FS-1, served as an 50 experimental (FS) variant, and bacteria cultivated on normal medium, served as negative control 51 (NC). RNA sequencing showed a differential gene expression in the FS-1 treated strain that may 52 explain the observed increase in susceptibility to gentamicin and ampicillin. Application of the 53 3 rd generation sequencing technology, SMRT PacBio, allowed an unambiguous whole genome 54 assembly of NC and FS variants, a...

News of the National Academy of Sciences of the Republic of Kazakhstan. Series of biology and medicine.

No abstract

Б а с р е д а к т о р ы х. ғ. д., проф., ҚР ҰҒА академигі М. Ж. Жұрынов Р е д а к ц и я а л қ а с ы:Ресей) Абишев М.Е. проф., корр.-мүшесі (Қазақстан) Аврамов К.В. проф. (Украина) Аппель Юрген проф. (Германия) Баймуқанов Д.А. проф., корр.-мүшесі (Қазақстан) Байтулин И.О. проф., академик (Қазақстан) Банас Иозеф проф. (Польша) Берсимбаев Р.И. проф., академик (Қазақстан) Велесько С. проф. (Германия) Велихов Е.П. проф., РҒА академигі (Ресей) Гашимзаде Ф. проф., академик (Əзірбайжан) Гончарук В.В. проф., академик (Украина) Давлетов А.Е. проф., корр.-мүшесі (Қазақстан) Джрбашян Р.Т. проф., академик (Армения) Қалимолдаев М.Н. проф., академик (Қазақстан), бас ред. орынбасары Лаверов Н.П. проф., академик РАН (Россия) Лупашку Ф. проф., корр.-мүшесі (Молдова) Мохд Хасан Селамат проф. (Малайзия) Мырхалықов Ж.У. проф., академик (Қазақстан) Новак Изабелла проф. (Польша) Огарь Н.П. проф., корр.-мүшесі (Қазақстан) Полещук О.Х. проф. (Ресей) Поняев А.И. проф. (Ресей) Сагиян А.С. проф., академик (Армения) Сатубалдин С.С. проф., академик (Қазақстан) Таткеева Г.Г. проф., корр.-мүшесі (Қазақстан) Умбетаев И. проф., академик (Қазақстан) Хрипунов Г.С. проф. (Украина) Юлдашбаев Ю.А. проф., РҒА корр-мүшесі (Ресей) Якубова М.М. проф., академик (Тəжікстан) «Қазақстан Республикасы Ұлттық ғылым академиясының Хабаршысы».

The problem of nosocomial infections is growing due to the introduction of new treatment regimens involving immunosuppressive drugs. The genomes of seven Gram-negative clinical isolates of Escherichia , Klebsiella , and Pseudomonas were sequenced and analyzed in this study to serve as model microorganisms to study drug-induced antibiotic resistance reversion.