scholarly journals 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

mSystems ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Ilya S. Korotetskiy ◽  
Sergey V. Shilov ◽  
Tatyana V. Kuznetsova ◽  
Aleksandr I. Ilin ◽  
Monique Joubert ◽  
...  

ABSTRACT 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.

2020 ◽  
Author(s):  
Ilya S. Korotetskiy ◽  
Sergey V. Shilov ◽  
Tatyana V. Kuznetsova ◽  
Aleksandr I. Ilin ◽  
Monique Joubert ◽  
...  

AbstractIodine is one of the oldest antimicrobial agents. Till 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 and the mid of the logarithmic growth phases. 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 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, osmotic and oxidative stresses leading to DNA damaging were the major factors influencing the treated bacteria.IMPORTANCEInfections caused by antibiotic resistant bacteria threaten the public health worldwide. Combinatorial therapy when antibiotics are administrated together with supplementary drugs improving susceptibility of pathogens to the 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 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.


2017 ◽  
Vol 5 (18) ◽  
Author(s):  
Muhammad A. Rehman ◽  
Catherine Carrillo ◽  
François Malouin ◽  
Moussa S. Diarra

ABSTRACT Enterohemorrhagic Escherichia coli serotype O157:H7 is a major cause of foodborne outbreaks and hemolytic-uremic syndrome. Here, we report the draft genome sequences of three antibiotic-resistant E. coli O157:H7 strains isolated from feedlot cattle. These draft genome sequences will aid in the development of sequence-based tools for the detection of virulence and antimicrobial resistance genotypes.


2021 ◽  
Vol 10 (31) ◽  
Author(s):  
Amanda Chamieh ◽  
Rita Zgheib ◽  
Sabah El-Sawalhi ◽  
Eid Azar ◽  
Jean-Marc Rolain

We present the genome sequences of two carbapenemase-producing sequence type 405 Escherichia coli clinical isolates, strains Marseille-Q1950 and Marseille-Q1951. The isolates were obtained 1 month apart during the patient’s hospitalization in Lebanon, in May (Marseille-Q1950) and June (Marseille-Q1951) 2019. The genome sizes of strains Marseille-Q1950 and Marseille-Q1951 were 5,181,515 bp and 5,213,451 bp, respectively.


mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Wooseong Kim ◽  
Guijin Zou ◽  
Wen Pan ◽  
Nico Fricke ◽  
Hammad A. Faizi ◽  
...  

ABSTRACT Resistance or tolerance to traditional antibiotics is a challenging issue in antimicrobial chemotherapy. Moreover, traditional bactericidal antibiotics kill only actively growing bacterial cells, whereas nongrowing metabolically inactive cells are tolerant to and therefore “persist” in the presence of legacy antibiotics. Here, we report that the diarylurea derivative PQ401, previously characterized as an inhibitor of the insulin-like growth factor I receptor, kills both antibiotic-resistant and nongrowing antibiotic-tolerant methicillin-resistant Staphylococcus aureus (MRSA) by lipid bilayer disruption. PQ401 showed several beneficial properties as an antimicrobial lead compound, including rapid killing kinetics, low probability for resistance development, high selectivity to bacterial membranes compared to mammalian membranes, and synergism with gentamicin. In contrast to well-studied membrane-disrupting cationic antimicrobial low-molecular-weight compounds and peptides, molecular dynamic simulations supported by efficacy data demonstrate that the neutral form of PQ401 penetrates and subsequently embeds into bacterial lipid bilayers more effectively than the cationic form. Lastly, PQ401 showed efficacy in both the Caenorhabditis elegans and Galleria mellonella models of MRSA infection. These data suggest that PQ401 may be a lead candidate for repurposing as a membrane-active antimicrobial and has potential for further development as a human antibacterial therapeutic for difficult-to-treat infections caused by both drug-resistant and -tolerant S. aureus. IMPORTANCE Membrane-damaging antimicrobial agents have great potential to treat multidrug-resistant or multidrug-tolerant bacteria against which conventional antibiotics are not effective. However, their therapeutic applications are often hampered due to their low selectivity to bacterial over mammalian membranes or their potential for cross-resistance to a broad spectrum of cationic membrane-active antimicrobial agents. We discovered that the diarylurea derivative compound PQ401 has antimicrobial potency against multidrug-resistant and multidrug-tolerant Staphylococcus aureus. PQ401 selectively disrupts bacterial membrane lipid bilayers in comparison to mammalian membranes. Unlike cationic membrane-active antimicrobials, the neutral form of PQ401 rather than its cationic form exhibits maximum membrane activity. Overall, our results demonstrate that PQ401 could be a promising lead compound that overcomes the current limitations of membrane selectivity and cross-resistance. Also, this work provides deeper insight into the design and development of new noncharged membrane-targeting therapeutics to combat hard-to-cure bacterial infections.


2018 ◽  
Vol 7 (20) ◽  
Author(s):  
Armando Hernández-Mendoza ◽  
Daniel Rivera Mendoza ◽  
Abimael Moran-Vazquez ◽  
Edgar Dantán-González

We report here the draft genome sequence of Escherichia coli strain BOq 01, a bacterium isolated from a poultry farm; the genome includes two plasmids conferring antibiotic resistances. This bacterium has a GC content of 50.89% and a genome size of 4.6 Mb.


2019 ◽  
Vol 8 (23) ◽  
Author(s):  
Vicente Gomez-Alvarez ◽  
Jill Hoelle

The spread of antibiotic-resistant microorganisms is a major public health concern. Here, we report the draft genome sequences of three Escherichia coli isolates from primary effluent collected from geographically dispersed U.S.


2015 ◽  
Vol 59 (7) ◽  
pp. 4031-4039 ◽  
Author(s):  
Joe A. Lemire ◽  
Lindsay Kalan ◽  
Alexandru Bradu ◽  
Raymond J. Turner

ABSTRACTHistorically it has been accepted, and recent research has established, that silver (Ag) is an efficacious antimicrobial agent. A dwindling pipeline of new antibiotics, combined with an increase in the number of antibiotic-resistant infections, is bringing Ag to the fore as a therapeutic compound to treat infectious diseases. Currently, many formulations of Ag are being deployed for commercial and medical purposes, with various degrees of effectiveness at killing microbial cells. Here, we evaluated the antimicrobial and antibiofilm capacity of our lead compound, silver oxynitrate [Ag(Ag3O4)2NO3or Ag7NO11], against other metal compounds with documented antimicrobial activity, including Ag2SO4, AgNO3, silver sulfadiazine (AgSD), AgO, Ag2O, and CuSO4. Our findings reveal that Ag7NO11eradicates biofilm and planktonic populations ofPseudomonas aeruginosa,Escherichia coli,Staphylococcus aureus, uropathogenicEscherichia coli(UPEC), fluoroquinolone-resistantPseudomonas aeruginosa(FQRP), and methicillin-resistantStaphylococcus aureus(MRSA) at lower concentrations than those of the other tested metal salts. Altogether, our results demonstrate that Ag7NO11has an enhanced efficacy for the treatment of biofilm-forming pathogens.


2021 ◽  
Vol 10 (11) ◽  
Author(s):  
Sara A. Burgess ◽  
Margaux Francois ◽  
Anne C. Midwinter ◽  
Patrick J. Biggs

ABSTRACT Draft genomes of seven extended-spectrum β-lactamase (ESBL)-producing Escherichia coli strains recovered from New Zealand waterways are described. The mean genome size was 5.1 Mb, with 4,724 coding sequences. All genomes contained the ESBL gene blaCTX-M, and one carried a plasmid-mediated AmpC gene, blaCMY-2. A multidrug-resistant genotype was detected in three isolates.


2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Johanne Blais ◽  
Sara Lopez ◽  
Cindy Li ◽  
Alexey Ruzin ◽  
Srijan Ranjitkar ◽  
...  

ABSTRACTLYS228 is a novel monobactam with potent activity againstEnterobacteriaceae. LYS228 is stable to metallo-β-lactamases (MBLs) and serine carbapenemases, includingKlebsiella pneumoniaecarbapenemases (KPCs), resulting in potency against the majority of extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistantEnterobacteriaceaestrains tested. Overall, LYS228 demonstrated potent activity against 271Enterobacteriaceaestrains, including multidrug-resistant isolates. Based on MIC90values, LYS228 (MIC90, 1 μg/ml) was ≥32-fold more active against those strains than were aztreonam, ceftazidime, ceftazidime-avibactam, cefepime, and meropenem. The tigecycline MIC90was 4 μg/ml against the strains tested. AgainstEnterobacteriaceaeisolates expressing ESBLs (n= 37) or displaying carbapenem resistance (n= 77), LYS228 had MIC90values of 1 and 4 μg/ml, respectively. LYS228 exhibited potent bactericidal activity, as indicated by low minimal bactericidal concentration (MBC) to MIC ratios (MBC/MIC ratios of ≤4) against 97.4% of theEnterobacteriaceaestrains tested (264/271 strains). In time-kill studies, LYS228 consistently achieved reductions in CFU per milliliter of 3 log10units (≥99.9% killing) at concentrations ≥4× MIC forEscherichia coliandK. pneumoniaereference strains, as well as isolates encoding TEM-1, SHV-1, CTX-M-14, CTX-M-15, KPC-2, KPC-3, and NDM-1 β-lactamases.


mSphere ◽  
2021 ◽  
Author(s):  
Kohei Kondo ◽  
Mitsuoki Kawano ◽  
Motoyuki Sugai

Although we believe phages play an important role in horizontal gene transfer in exchanging genetic material, we do not know the distribution of the antimicrobial resistance (AMR) and/or virulence factor (VF) genes in prophages. We collected different prophage elements from the complete genome sequences of seven species— Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , Enterobacter cloacae , and Escherichia coli —and characterized the distribution of antimicrobial resistance and virulence genes encoded in the prophage region.


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