Complete Genome Sequence of a Multidrug-Resistant Strain, Escherichia coli ATCC BAA-196, as a Model for Studying Induced Antibiotic Resistance Reversion

Korotetskiy, Ilya S.; Joubert, Monique; Taukobong, Setshaba; Jumagaziyeva, Ardak B.; Shilov, Sergey V.; Shvidko, Sergey V.; Suldina, Natalya A.; Kenesheva, Sabina T.; Yssel, Anna; Reva, Oleg N.; Il’in, A. I.

doi:10.1128/mra.01118-19

Cited by 6 publications

(7 citation statements)

References 14 publications

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“…In total, the expression of 2,952 protein or regulatory RNA coding genes of S. aureus BAA-39 participating basically in all biological processes were affected during 10 passages of the cultivation with FS-1 ( Supplementary Table S1). Further study will aim at identification and experimental validation of common mechanisms of action of iodine-containing nanomicelles on taxonomically distant microorganisms, S. aureus, E. coli (Korotetskiy et al, 2019a(Korotetskiy et al, , 2020b, A. baumannii (Korotetskiy et al, 2020a) and M. tuberculosis (Ilin et al, 2015(Ilin et al, , 2017. The drug FS-1 has successful passed clinical trials in Kazakhstan as a supplement of the antibiotic therapy against multidrug resistant tuberculosis 4 (acc.…”

Section: Resultsmentioning

confidence: 99%

“…Epigenetic mechanisms of antibiotic resistance reversion were hypothesized. Later, the antibiotic resistance reversion was reproduced on beta-lactam antibiotic resistant strain Escherichia coli ATCC BAA-196 TM (Korotetskiy et al, 2019a) and MRSA Staphylococcus aureus ATCC BAA-39 TM (Joubert et al, 2019), which are more suitable for laboratory experiments than XDR TB.…”

Section: Introductionmentioning

confidence: 99%

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The Effect of Iodine-Containing Nano-Micelles, FS-1, on Antibiotic Resistance, Gene Expression and Epigenetic Modifications in the Genome of Multidrug Resistant MRSA Strain Staphylococcus aureus ATCC BAA-39

Reva

Korotetskiy²,

Joubert

et al. 2020

Front. Microbiol.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Effect of Iodine-Containing Nano-Micelles, FS-1, on Antibiotic Resistance, Gene Expression and Epigenetic Modifications in the Genome of Multidrug Resistant MRSA Strain Staphylococcus aureus ATCC BAA-39

Reva

Korotetskiy²,

Joubert

et al. 2020

Front. Microbiol.

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“…Studying of mechanisms of the therapeutic activity of this drug was hampered by obvious technical problems of using MDR-TB isolates as model organisms. Reproduction of antibiotic resistance reversion by FS-1 on E. coli [12] and S. aureus [9,13] E. coli ATCC BAA-196 is a laboratory strain constructed by inserting plasmid pMG223 from K. pneumoniae ATCC 14714 bearing multiple antibiotic resistance determinants into nonpathogenic and antibiotic-susceptible strain E. coli J53-2 [14]. Contrary, the strain S. aureus BAA-39 used in other study is a natural MRSA strain bearing a horizontally acquired methicillin resistance cassette SCCmec [13].…”

Section: Discussionmentioning

confidence: 99%

“…The complete genome assembly was performed using SMRT Link 6.0.0 pipeline as published previously [13]. Two genome variants, NC and FS, were obtained by assembly of the joint pools of DNA reads of three sets of DNA samples generated from NC and FS cultures of E. coli .…”

Section: Genome Assembly and Annotationmentioning

confidence: 99%

Transcriptomics and methylomics study on the effect of iodine-containing drug FS-1 onEscherichia coliATCC BAA-196

Korotetskiy¹,

Jumagaziyeva²,

Shilov³

et al. 2020

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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...

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“…Acinetobacter baumannii BAA-1790. Complete genome sequences of these microorganisms were obtained using SMRT PacBio sequencing for two variants of the strains: the initial culture and the culture grown with sub-bactericidal concentrations of FS-1 in 10 daily passages [23][24][25]. Global genetic variations, epigenetic modifications and altered gene regulation in S. aureus BAA-39 and E. coli BAA-196 cultivated with FS-1 were analysed in recent publications [26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Comparison of transcriptional responses and metabolic alterations in three multidrug resistant model microorganisms,Staphylococcus aureusATCC BAA-39,Escherichia coliATCC BAA-196 andAcinetobacter baumanniiATCC BAA-1790, on exposure to iodine-containing nano-micelle drug FS-1

Korotetskiy

Shilov

Kuznetsova

et al. 2020

Preprint

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Iodine is one of the oldest antimicrobial agents. Till now there have been no reports on development of resistance to iodine. Recent studies showed promising results on the application of iodine-containing nano-micelles, FS-1, against antibiotic resistant pathogens as a supplement to antibiotic therapy. The mechanisms of action, however, remain unclear. The aim of this study was to perform a systemic analysis of gene regulation and metabolic alterations in three phylogenetically distant reference strains from ATCC culture collection representing multidrug resistant pathogens associated with nosocomial infections: Escherichia coli BAA-196, Staphylococcus aureus BAA-39 and Acinetobacter baumannii BAA-1790. These cultures were treated in 5 min exposure to sublethal doses of the iodine-containing drug FS-1 applied in the late lagging and the mid of the logarithmic growth phases. Complete genome sequences of these strains were obtained in previous studies. Gene regulation was studied by total RNA extraction and Ion Torrent sequencing followed by mapping the RNA reads against the reference genome sequences and statistical processing of read counts using the DESeq2 algorithm. It was found that the treatment of bacteria with FS-1 profoundly affected the expression of many genes involved in central metabolic pathways; however, alterations of gene expression profiles were species-specific and depended on the growth phase when the drug was applied. Disruption of respiratory electron-transfer membrane complexes, increased penetrability of bacterial cell wall, osmotic and oxidative stresses leading to DNA damage were the major factors influencing the treated bacteria.IMPORTANCEInfections caused by antibiotic resistant bacteria threaten public health worldwide. Combinatorial therapy when antibiotics are administrated together with supplementary drugs improving susceptibility of pathogens to regular antibiotics is considered as a promising way to overcome this problem. An induction of antibiotic resistance reversion by the iodine-containing nano-micelle drug FS-1 was reported recently. This drug is currently under clinical trials in Kazakhstan against multidrug resistant tuberculosis. The effect of iodine solutes on metabolic and regulatory processes in bacterial cells remain unexplored that precludes the effective application of iodine-containing antimicrobials in medicine. The current work provides an insight into gene regulation in antibiotic resistant bacteria treated with iodine-containing nanoparticles. Our expectation is that this study will shed light on unexplored bioactivities of iodine and the mechanisms of its antibacterial effect when applied in low concentrations. This knowledge will aid in future design of new drugs against antibiotic resistant infections.

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Complete Genome Sequence of a Multidrug-Resistant Strain, Escherichia coli ATCC BAA-196, as a Model for Studying Induced Antibiotic Resistance Reversion

Cited by 6 publications

References 14 publications

The Effect of Iodine-Containing Nano-Micelles, FS-1, on Antibiotic Resistance, Gene Expression and Epigenetic Modifications in the Genome of Multidrug Resistant MRSA Strain Staphylococcus aureus ATCC BAA-39

The Effect of Iodine-Containing Nano-Micelles, FS-1, on Antibiotic Resistance, Gene Expression and Epigenetic Modifications in the Genome of Multidrug Resistant MRSA Strain Staphylococcus aureus ATCC BAA-39

Transcriptomics and methylomics study on the effect of iodine-containing drug FS-1 onEscherichia coliATCC BAA-196

Comparison of transcriptional responses and metabolic alterations in three multidrug resistant model microorganisms,Staphylococcus aureusATCC BAA-39,Escherichia coliATCC BAA-196 andAcinetobacter baumanniiATCC BAA-1790, on exposure to iodine-containing nano-micelle drug FS-1

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