The antimicrobial effect of anti-dnaKpeptide nucleic acids on multidrug resistant strains ofEscherichia coliandSalmonella entericaserovar Typhimurium

Kiran, Dilara; Sriranganathan, Nammalwar

doi:10.1893/0005-3155-85.1.48

Cited by 5 publications

(5 citation statements)

References 9 publications

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“…Recently, numerous attempts have been made to block the bacterial chaperone dnaK in bacterial strains with multiple drug resistance. In this respect, an effect comparable to that of antibiotics was achieved with some strains of Salmonella [ 116 ].…”

Section: In Cellulo Applicationsmentioning

confidence: 99%

Artificial genetic polymers against human pathologies

et al. 2022

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Originally discovered by Nielsen in 1991, peptide nucleic acids and other artificial genetic polymers have gained a lot of interest from the scientific community. Due to their unique biophysical features these artificial hybrid polymers are now being employed in various areas of theranostics (therapy and diagnostics). The current review provides an overview of their structure, principles of rational design, and biophysical features as well as highlights the areas of their successful implementation in biology and biomedicine. Finally, the review discusses the areas of improvement that would allow their use as a new class of therapeutics in the future.

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Section: In Cellulo Applicationsmentioning

confidence: 99%

Artificial genetic polymers against human pathologies

et al. 2022

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“…The ability of PNA to inhibit pathogenic bacteria is also reported. Studies demonstrate that anti‐dnaK PNAs are mildly effective on E. coli and very effective on S. enterica strains in vitro . The growth of bacterial cultures is also inhibited in vitro by CPP–PNA molecular systems.…”

Section: Applicationsmentioning

confidence: 99%

“…Studies demonstrate that anti-dnaK PNAs are mildly effective on E. coli and very effective on S. enterica strains in vitro. [98] The growth of bacterial cultures is also inhibited in vitro by CPP-PNA molecular systems. Further, it was found that electroporation enhances the bioavailability of (KFF) 3 K-O-PNA and inhibits intracellular Salmonella inside macrophages.…”

Section: • Inhibition Of Transcription • Artificially Initiate Transcmentioning

confidence: 99%

Versatility of peptide nucleic acids (PNAs): role in chemical biology, drug discovery, and origins of life

Sharma

Awasthi

2016

Chem Biol Drug Des

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This review briefly discussed nomenclature, synthesis, chemistry, and biophysical properties of a plethora of PNA derivatives reported since the discovery of aegPNA. Different synthetic methods and structural analogs of PNA synthesized till date were also discussed. An insight was gained into various chemical, physical, and biological properties of PNA which make it preferable over all other classes of modified nucleic acid analogs. Thereafter, various approaches with special attention to the practical constraints, characteristics, and inherent drawbacks leading to the delay in the development of PNA as gene therapeutic drug were outlined. An explicit account of the successful application of PNA in different areas of research such as antisense and antigene strategies, diagnostics, molecular probes, and so forth was described along with the current status of PNA as gene therapeutic drug. Further, the plausibility of the existence of PNA and its role in primordial chemistry, that is, origin of life was explored in an endeavor to comprehend the mystery and open up its deepest secrets ever engaging and challenging the human intellect. We finally concluded it with a discussion on the future prospects of PNA technology in the field of therapeutics, diagnostics, and origin of life.

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“…13 These synthetic nucleic acids have been used to target a multitude of genes including LNA targeted against f tsZ in methicillin-resistant Staphylococcus aureus 19 and PNA targeted to dnaK in Escherichia coli and Salmonella enterica. 20 PNA, conjugated to cell penetrating peptides (CPPs) for increased transport into cells, has been used to target rRNA to disrupt protein synthesis and acp, to disrupt cell wall formation, in E. coli. 21 Although there are challenges associated with the delivery of antisense therapeutics, 13 the recent FDA approval of two antisense therapeutics, Fomivirsen for retinitis and Mipomersen for cholesterol reduction, highlights their potential use in practical applications.…”

mentioning

confidence: 99%

“…Antisense therapeutics are nucleotide sequence based therapeutics that target specific RNA or DNA sequences and interact via complementary Watson–Crick base pairing between the target and antisense sequence, , thereby causing decrease in gene expression by blocking transcription, ribosomal binding, preventing ribosomal migration, or inducing cleavage by RNases. , Antisense therapies are not limited to natural nucleic acids, , but can also utilize synthetic nucleic acids such as locked nucleic acids (LNA), bicyclic nucleic acids (BNA), and peptide nucleic acids (PNA), among others . These synthetic nucleic acids have been used to target a multitude of genes including LNA targeted against ftsZ in methicillin-resistant Staphylococcus aureus and PNA targeted to dnaK in Escherichia coli and Salmonella enterica . PNA, conjugated to cell penetrating peptides (CPPs) for increased transport into cells, has been used to target rRNA to disrupt protein synthesis and acp , to disrupt cell wall formation, in E. coli .…”

mentioning

confidence: 99%

Sequence-Specific Peptide Nucleic Acid-Based Antisense Inhibitors of TEM-1 β-Lactamase and Mechanism of Adaptive Resistance

Courtney

Chatterjee

2015

ACS Infect. Dis.

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The recent surge of drug-resistant superbugs and shrinking antibiotic pipeline are serious challenges to global health. In particular, the emergence of β-lactamases has caused extensive resistance against the most frequently prescribed class of β-lactam antibiotics. Here, we develop novel synthetic peptide nucleic acid-based antisense inhibitors that target the start codon and ribosomal binding site of the TEM-1 β-lactamase transcript and act via translation inhibition mechanism. We show that these antisense inhibitors are capable of resensitizing drug-resistant Escherichia coli to β-lactam antibiotics exhibiting 10-fold reduction in the minimum inhibitory concentration (MIC). To study the mechanism of resistance, we adapted E. coli at MIC levels of the β-lactam/antisense inhibitor combination and observed a nonmutational, bet-hedging based adaptive antibiotic resistance response as evidenced by phenotypic heterogeneity as well as heterogeneous expression of key stress response genes. Our data show that both the development of new antimicrobials and an understanding of cellular response during the development of tolerance could aid in mitigating the impending antibiotic crisis.

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The antimicrobial effect of anti-dnaKpeptide nucleic acids on multidrug resistant strains ofEscherichia coliandSalmonella entericaserovar Typhimurium

Cited by 5 publications

References 9 publications

Artificial genetic polymers against human pathologies

Artificial genetic polymers against human pathologies

Versatility of peptide nucleic acids (PNAs): role in chemical biology, drug discovery, and origins of life

Sequence-Specific Peptide Nucleic Acid-Based Antisense Inhibitors of TEM-1 β-Lactamase and Mechanism of Adaptive Resistance

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