Selective killing of antibiotic-resistant bacteria from within

Koskiniemi, Sanna; Virtanen, Petra

doi:10.1038/d41586-019-01852-w

Cited by 7 publications

(5 citation statements)

References 6 publications

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“…In recent years, the emergence of antibiotic-resistant bacteria has become a global problem. One of the main drivers for the emergence of antibiotic-resistant bacteria is the excessive or inappropriate use of antibiotics [ 1 , 2 ].…”

Section: Introductionmentioning

confidence: 99%

Antibiotic-Resistant and Non-Resistant Bacteria Display Similar Susceptibility to Dielectric Barrier Discharge Plasma

Sakudo

Misawa

2020

IJMS

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Here, we examined whether antibiotic-resistant and non-resistant bacteria show a differential susceptibility to plasma treatment. Escherichia coli DH5α were transformed with pPRO-EX-HT-CAT, which encodes an ampicillin resistance gene and chloramphenicol acetyltransferase (CAT) gene, and then treated with a dielectric barrier discharge (DBD) plasma torch. Plasma treatment reduced the viable cell count of E. coli after transformation/selection and further cultured in ampicillin-containing and ampicillin-free medium. However, there was no significant difference in viable cell count between the transformed and untransformed E. coli after 1 min- and 2 min-plasma treatment. Furthermore, the enzyme-linked immunosorbent assay (ELISA) and acetyltransferase activity assay showed that the CAT activity was reduced after plasma treatment in both transformed and selected E. coli grown in ampicillin-containing or ampicillin-free medium. Loss of lipopolysaccharide and DNA damage caused by plasma treatment were confirmed by a Limulus test and polymerase chain reaction, respectively. Taken together, these findings suggest the plasma acts to degrade components of the bacteria and is therefore unlikely to display a differential affect against antibiotic-resistant and non-resistant bacteria. Therefore, the plasma method may be useful in eliminating bacteria that are recalcitrant to conventional antibiotic therapy.

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Section: Introductionmentioning

confidence: 99%

Antibiotic-Resistant and Non-Resistant Bacteria Display Similar Susceptibility to Dielectric Barrier Discharge Plasma

Sakudo

Misawa

2020

IJMS

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“…However, the scattergun overuse of antibiotics tends to promote the emergence of antibiotic-resistant (ABR) bacteria. Moreover, broad-spectrum antibiotics kill not only pathogenic bacteria, but also bene cial bacteria [1][2][3] . Meanwhile, CRISPR-Cas therapy, engineered toxins and stapled antimicrobial peptides have recently emerged as targeted and effective antimicrobials [4][5][6][7][8][9] .…”

Section: Full Textmentioning

confidence: 99%

“…The amount of linked GP is 2.5, 5, 10 or 15 mg mL -1 . GP-SiNPs-asPNA and (KFF)3 K-asPNA are loaded with the same amount of asPNA (e.g., 1 μM). e, Confocal uorescence images of the mixture of ARPE-19 and MDR E. coli (ARPE-19 + MDR E. coli, Control), (ARPE-19 + MDR E. coli) treated with GP-SiNPs-asPNA, (ARPE-19 + MDR E. coli) treated with (KFF) 3 K-asPNA, and confocal uorescence images of the mixture of ARPE-19 and MRSA (ARPE-19 + MRSA, Control), (ARPE-19 + MRSA) treated with GP-SiNPs-asPNA, (ARPE-19 + MRSA) treated with (KFF) 3 K-asPNA.…”

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confidence: 99%

Antisense oligonucleotides selectively enter human-derived antibiotic-resistant bacteria through ATP-binding cassette transporter

Liu¹,

Sun

Ding

et al. 2022

Preprint

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The current vehicles used to deliver antisense oligonucleotides (ASOs) cannot distinguish between bacterial and mammalian cells, greatly hindering the preclinical or clinical treatment of bacterial infections, especially those caused by antibiotic-resistant bacteria. Herein, we leverage bacteria-specific ATP-binding cassette (ABC) transporters to selectively internalize ASOs by hitchhiking them on the unique carbon source of bacterial cells. Compared with their cell-penetrating peptide counterparts, which are non-specifically engulfed by both mammalian and bacterial cells and which display a low uptake rate (i.e. 14.7%), the presented therapeutics consisting of glucose polymer and antisense peptide nucleic acid-modified nanoparticles are selectively internalized into the human-derived multidrug-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus, and they display a much higher uptake rate (i.e. 51.6%). We demonstrate that the developed strategy allows specific and efficient killing of nearly 100% of the antibiotic-resistant bacteria. We also show its significant curative efficacy against bacterial keratitis and endophthalmitis in mice. This strategy will expand the focus of antisense technology to include bacterial cells other than mammalian cells.

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“…Moreover, broad-spectrum antibiotics kill not only pathogenic bacteria, but also beneficial bacteria. [1][2][3] Meanwhile, CRISPR-Cas therapy, engineered toxins, and stapled antimicrobial peptides have recently emerged as targeted and effective antimicrobials. [4][5][6][7][8][9] Unlike these antimicrobials, antisense oligonucleotides (ASOs) can target specific bacterial genes and inhibit transcription through complementary base pairing, significantly expanding the available therapeutic targets, even in ABR bacteria.…”

Section: Introductionmentioning

confidence: 99%

Antisense Oligonucleotides Selectively Enter Human‐Derived Antibiotic‐Resistant Bacteria through Bacterial‐Specific ATP‐Binding Cassette Sugar Transporter

et al. 2023

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Current vehicles used to deliver antisense oligonucleotides (ASOs) cannot distinguish between bacterial and mammalian cells, greatly hindering the preclinical or clinical treatment of bacterial infections, especially those caused by antibiotic‐resistant bacteria. Herein, bacteria‐specific ATP‐binding cassette (ABC) sugar transporters are leveraged to selectively internalize ASOs by hitchhiking them on α (1–4)‐glucosidically linked glucose polymers. Compared with their cell‐penetrating peptide counterparts, which are non‐specifically engulfed by mammalian and bacterial cells, the presented therapeutics consisting of glucose polymer and antisense peptide nucleic‐acid‐modified nanoparticles are selectively internalized into the human‐derived multidrug‐resistant Escherichia coli and methicillin‐resistant Staphylococcus aureus, and they display a much higher uptake rate (i.e., 51.6%). The developed strategy allows specific and efficient killing of nearly 100% of the antibiotic‐resistant bacteria. Its significant curative efficacy against bacterial keratitis and endophthalmitis is also shown. This strategy will expand the focus of antisense technology to include bacterial cells other than mammalian cells.

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Selective killing of antibiotic-resistant bacteria from within

Cited by 7 publications

References 6 publications

Antibiotic-Resistant and Non-Resistant Bacteria Display Similar Susceptibility to Dielectric Barrier Discharge Plasma

Antibiotic-Resistant and Non-Resistant Bacteria Display Similar Susceptibility to Dielectric Barrier Discharge Plasma

Antisense oligonucleotides selectively enter human-derived antibiotic-resistant bacteria through ATP-binding cassette transporter

Antisense Oligonucleotides Selectively Enter Human‐Derived Antibiotic‐Resistant Bacteria through Bacterial‐Specific ATP‐Binding Cassette Sugar Transporter

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