Phages produce persisters

Microbial Biotechnology, Journal Year: 2024, Volume and Issue: 17(8)

Published: Aug. 1, 2024

Arguably, the greatest threat to bacteria is phages. It often assumed that those escape phage infection have mutated or utilized phage-defence systems; however, another possibility a subpopulation forms dormant persister state in manner similar demonstrated for bacterial cells undergoing nutritive, oxidative, and antibiotic stress. Persister do not undergo mutation survive lethal conditions by ceasing growth transiently. Slower dormancy play key physiological role as they allow host defence systems more time clear infection. Here, we investigated how lytic isolating surviving from plaques of T2, T4, lambda (cI mutant) virulent phages sequencing their genomes. We found can attack both (i.e. become resistant) without persistent). Specifically, whereas T4-resistant lambda-resistant with over 100,000-fold less sensitivity were isolated obvious genetic mutations (e.g. causing mucoidy), also after T2 no significant mutation, retain wild-type sensitivity, doses antibiotics. Corroborating this, adding resulted 137,000-fold survival compared addition exponentially growing cells. Furthermore, our results seem general treatments Klebsiella pneumonia Pseudomonas aeruginosa generated Hence, along resistant strains, form during

Language: Английский

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Implications of lytic phage infections inducing persistence

Current Opinion in Microbiology, Journal Year: 2024, Volume and Issue: 79, P. 102482 - 102482

Published: May 6, 2024

Language: Английский

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Mitomycin C as an Anti-Persister Strategy against Klebsiella pneumoniae: Toxicity and Synergy Studies

Antibiotics, Journal Year: 2024, Volume and Issue: 13(9), P. 815 - 815

Published: Aug. 28, 2024

The combination of several therapeutic strategies is often seen as a good way to decrease resistance rates, since bacteria can more easily overcome single-drug treatments than multi-drug ones. This strategy especially attractive when targets and subpopulations are affected, it the case Klebsiella pneumoniae persister cells, subpopulation able transiently survive antibiotic exposures. work aims evaluate potential repurposed anticancer drug, mitomycin C, combined with K. lytic phage vB_KpnM-VAC13 in vitro its safety an vivo murine model against two clinical isolates this pathogen, one them exhibiting imipenem-persister phenotype. At same time, we verified absence toxicity C at concentration using human chondrocyte cell line T/C28a2. viability these cells was checked both cytotoxicity assays flow cytometry.

Language: Английский

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Diverse physiological roles of the MqsR/MqsA toxin/antitoxin system

Deleted Journal, Journal Year: 2024, Volume and Issue: 1(1)

Published: Jan. 1, 2024

Abstract There is tremendous interest in the use of bacteriophages (phages) to combat multi-drug resistant bacteria. However, implement successfully phage therapy, host defense systems must be understood. Toxin/antitoxins (TAs) are most prevalent system, and MqsR/MqsA TA system one best-studied systems. This phage-defense was discovered a whole-cell, population-averaged, transcriptome study designed elucidate biofilm-related genes Escherichia coli 2004. Biofilms cells cemented themselves or surfaces. Since its characterization (as April 2024), has been utilized over 1200 manuscripts, although role cell physiology contested. Here, we summarize important physiological roles this including (i) general stress response via repression rpoS, (ii) biofilm formation csgA, (iii) combating bile acid gastrointestinal tract by inhibiting uptake salt deoxycholate, (iv) oxidative based on single-cell studies, (v) leading persister state.

Language: Английский

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Phages Produce Persisters

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 17, 2023

SUMMARY Bacteria primarily encounter stress, and, arguably, their greatest threats are phages. It is often assumed that those bacteria escape phage attack have mutated; however, another possibility a subpopulation forms the dormant persister state, in manner similar to demonstrated for bacterial cells undergoing nutritive, oxidative, and antibiotic stress. Persister do not undergo mutation survive lethal conditions by ceasing growth transiently. Slower dormancy play key physiological role as they allow host defense systems more time clear infection. Here we investigated how lytic infection isolating surviving from plaques of T2, T4, lambda (cI mutant) virulent We found can both (i.e., become resistant) without persistent). Specifically, whereas T4-resistant lambda-resistant with over 100,000-fold less sensitivity were isolated obvious genetic mutations (e.g., causing mucoidy), also after T2 no significant mutation, retain wild-type sensitivity, doses antibiotics. Corroborating this, adding resulted 137,000-fold survival compared addition exponentially-growing cells. Phage treatments Klebsiella pneumonia Pseudomonas aeruginosa generated Hence, along resistant strains, form during

Language: Английский

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Mitomycin C as an Anti-persister Strategy Against Klebsiella Pneumoniae: Toxicity and Synergy Studies

Published: Aug. 6, 2024

The combination of several therapeutic strategies is often seen as a good way to decrease the resistance rates, since bacteria overcome better single-drug treatments than multi-drug ones. This strategy especially attractive when targets and subpopulations are affected, it case Klebsiella pneumoniae persister cells, subpopulation able transiently survive antibiotic exposures. work aims evaluate potential repurposed anticancer drug, mitomycin C, combined with K. lytic phage vB_KpnM-VAC13 in vitro safety an vivo murine model against two clinical isolates this pathogen, one them exhibiting imipenem-persister phenotype. At same time, we verified absence toxicity C at concentration using human chondrocyte cell line T/C28a2. viability these cells was checked both by cytotoxicity assays flow cytometry.

Language: Английский

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