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, Oleg N.; Korotetskiy, Ilya S.; Joubert, Monique; Shilov, Sergey V.; Jumagaziyeva, Ardak B.; Suldina, Natalya A.; Il’in, A. I.

doi:10.3389/fmicb.2020.581660

Cited by 12 publications

(20 citation statements)

References 92 publications

(125 reference statements)

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“…This caused bacteria to look for alternative electron acceptors such as DMSO in the case with E. coli or nitrates/nitrites in the case with S. aureus. In another study on E. coli BAA-196 cultivated for 10 passages with FS-1, a complete stall of expression of genes encoding cytochrome bo terminal oxidase complex (cyoA, cyoB, cyoC and cyoE) was observed[26,28] that corroborates with the hypothesis that iodine may interfere with the systems of electron transportation between cytochromes and oxygen. This transition to anaerobiosis caused by the treatment with FS-1 may be of practical 20 importance.…”

supporting

confidence: 68%

“…The scheme of the regulated metabolic pathways is shown Genes pyrH, lpxH and fabF involved in the nucleotide and fatty acid biosynthesis were downregulated while the nucleotide degradation and salvage genes ppnP and rutF were upregulated. A strong downregulation was observed for the potassium uptake proteins KdpABCD, which play an important role in maintenance of osmotic homeostasis [38,40] and in the adaptation of E. coli to the presence of FS-1 in the medium [26]. Peptidoglycan synthesis and assembly genes murI and dacA; and heavy metal resistance genes copA and spxA were strongly upregulated in FS-1 treated A. baumannii as it was observed also in the FS-1 treated E. coli and S. aureus.…”

Section: Differential Gene Expression In a Baumannii Atcc Baa-1790mentioning

confidence: 99%

“…In S. aureus, the elevated accumulation of iodine in cytoplasm caused stronger damaging of DNA that was apparent by the observed activation of DNA repair and nucleotide salvage systems. Another study when S. aureus was cultivated for long time with FS-1 showed an increased rate of mutations and abnormal epigenetic modifications of the chromosomal DNA[26]. This activation of the DNA repair systems in response to the treatment with FS-1 was not observed in other two bacteria.…”

mentioning

confidence: 92%

“…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]. The aim of the current study was to perform a systemic analysis of gene expression and metabolic alteration in these three selected multidrug resistant pathogens affected by a 5 min exposure to the sublethal dose of the iodine-containing drug FS-1 in the late lagging and the mid of the logarithmic growth phases.…”

Section: Introductionmentioning

confidence: 99%

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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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supporting

confidence: 68%

Section: Differential Gene Expression In a Baumannii Atcc Baa-1790mentioning

confidence: 99%

mentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Self Cite

View full text Add to dashboard Cite

show abstract

mentioning

confidence: 99%

Comparison of Transcriptional Responses and Metabolic Alterations in Three Multidrug-Resistant Model Microorganisms, Staphylococcus aureus ATCC BAA-39, Escherichia coli ATCC BAA-196, and Acinetobacter baumannii ATCC BAA-1790, on Exposure to Iodine-Containing Nano-micelle Drug FS-1

Korotetskiy¹,

Shilov²,

Кузнецова³

et al. 2021

mSystems

Self Cite

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Iodine is one of the oldest antimicrobial agents. Until now, there have been no reports on acquiring resistance to iodine. Recent studies showed promising results on application of iodine-containing nano-micelles, FS-1, against antibiotic-resistant pathogens as a supplement to antibiotic therapy. The mechanisms of the action, however, remain unclear. The aim of this study was to perform a holistic analysis and comparison of gene regulation in three phylogenetically distant multidrug-resistant reference strains representing pathogens associated with nosocomial infections from the ATCC culture collection: Escherichia coli BAA-196, Staphylococcus aureus BAA-39, and Acinetobacter baumannii BAA-1790. These cultures were treated by a 5-min exposure to sublethal concentrations of the iodine-containing drug FS-1 applied in the late lagging phase and the middle of the logarithmic growth phase. Complete genome sequences of these strains were obtained in the 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 the central metabolic pathways; however, alterations of the gene expression profiles were species specific and depended on the growth phase. Disruption of respiratory electron transfer membrane complexes, increased penetrability of bacterial cell walls, and osmotic and oxidative stresses leading to DNA damage were the major factors influencing the treated bacteria. IMPORTANCE Infections caused by antibiotic-resistant bacteria threaten public health worldwide. Combinatorial therapy in which antibiotics are administered together with supplementary drugs improving susceptibility of pathogens to the regular antibiotics is considered a promising way to overcome this problem. An induction of antibiotic resistance reversion by the iodine-containing nano-micelle drug FS-1 has been reported recently. This drug is currently under clinical trials in Kazakhstan against multidrug-resistant tuberculosis. The effects of released iodine on metabolic and regulatory processes in bacterial cells remain unexplored. The current work provides an insight into gene regulation in the antibiotic-resistant nosocomial reference strains treated with iodine-containing nanoparticles. This study sheds light on unexplored bioactivities of iodine and the mechanisms of its antibacterial effect when applied in sublethal concentrations. This knowledge will aid in the future design of new drugs against antibiotic-resistant infections.

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The Phytochemical Tactics for Battling Antibiotic Resistance in Microbes: Secondary Metabolites and Nano Antibiotics Methods

Adam

Tandon

et al. 2023

Chemistry & Biodiversity

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One of the most serious threats to human health is antibiotic resistance, which has left the world without effective antibiotics. While continuous research and inventions for new antibiotics are going on, especially those with new modes of action, it is unlikely that this alone would be sufficient to win the battle. Furthermore, it is also important to investigate additional approaches. One such strategy for improving the efficacy of existing antibiotics is the discovery of adjuvants. This review has collected data from various studies on the current crisis and approaches for combating multi‐drug resistance in microbial pathogens using phytochemicals. In addition, the nano antibiotic approaches, are discussed, highlighting the high potentials of essential oils, alkaloids, phenolic compounds, and nano antibiotics in combating antibiotic resistance.

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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

Cited by 12 publications

References 92 publications

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

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

Comparison of Transcriptional Responses and Metabolic Alterations in Three Multidrug-Resistant Model Microorganisms, Staphylococcus aureus ATCC BAA-39, Escherichia coli ATCC BAA-196, and Acinetobacter baumannii ATCC BAA-1790, on Exposure to Iodine-Containing Nano-micelle Drug FS-1

The Phytochemical Tactics for Battling Antibiotic Resistance in Microbes: Secondary Metabolites and Nano Antibiotics Methods

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