Polyamines reduce oxidative stress in Escherichia coli cells exposed to bactericidal antibiotics

Ткаченко, А. Г.; Akhova, A. V.; Шумков, М. С.; Nesterova, L. Yu.

doi:10.1016/j.resmic.2011.10.009

Cited by 96 publications

(73 citation statements)

References 26 publications

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“…Thus, our results demonstrating a protective role for putrescine in the response to the oxidative stress generated in B. cenocepacia during antibiotic exposure represent another mechanism of protection from the antibacterial effects of bactericidal antibiotics. This agrees with previous reports on the antioxidant properties and protective effects of putrescine against antibiotic-induced ROS formation in E. coli (17).…”

Section: Figsupporting

confidence: 93%

“…However, polyamines can also quench oxidative species (14) and protect membranes from lipid peroxidation (15). Various classes of antibiotics induce oxidative stress and increased production of reactive oxygen species (ROS) (16)(17)(18)(19). Although the specific lethal role of ROS generated in response to antibiotics remains under discussion (16,20,21), oxidative stress constitutes a burden on the bacterial cells (22).…”

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confidence: 99%

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Putrescine Reduces Antibiotic-Induced Oxidative Stress as a Mechanism of Modulation of Antibiotic Resistance in Burkholderia cenocepacia

El-Halfawy

Valvano

2014

Antimicrob Agents Chemother

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cCommunication of antibiotic resistance among bacteria via small molecules is implicated in transient reduction of bacterial susceptibility to antibiotics, which could lead to therapeutic failures aggravating the problem of antibiotic resistance. Released putrescine from the extremely antibiotic-resistant bacterium Burkholderia cenocepacia protects less-resistant cells from different species against the antimicrobial peptide polymyxin B (PmB). Exposure of B. cenocepacia to sublethal concentrations of PmB and other bactericidal antibiotics induces reactive oxygen species (ROS) production and expression of the oxidative stress response regulator OxyR. We evaluated whether putrescine alleviates antibiotic-induced oxidative stress. The accumulation of intracellular ROS, such as superoxide ion and hydrogen peroxide, was assessed fluorometrically with dichlorofluorescein diacetate, while the expression of OxyR and putrescine synthesis enzymes was determined in luciferase assays using chromosomal promoter-lux reporter system fusions. We evaluated wild-type and isogenic deletion mutant strains with defects in putrescine biosynthesis after exposure to sublethal concentrations of PmB and other bactericidal antibiotics. Exogenous putrescine protected against oxidative stress induced by PmB and other antibiotics, whereas reduced putrescine synthesis resulted in increased ROS generation and a parallel increased sensitivity to PmB. Of the 3 B. cenocepacia putrescine-synthesizing enzymes, PmB induced only BCAL2641, an ornithine decarboxylase. This study reveals BCAL2641 as a critical component of the putrescine-mediated communication of antibiotic resistance and as a plausible target for designing inhibitors that would block the communication of such resistance among different bacteria, ultimately reducing the window of therapeutic failure in treating bacterial infections.

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Section: Figsupporting

confidence: 93%

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confidence: 99%

Putrescine Reduces Antibiotic-Induced Oxidative Stress as a Mechanism of Modulation of Antibiotic Resistance in Burkholderia cenocepacia

El-Halfawy

Valvano

2014

Antimicrob Agents Chemother

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“…Consistent with prior studies on antibiotic tolerance3031, central components of the stringent response (SpoT and SspA) were occasional targets of selection. Antioxidant stress response (SoxR and AhpF)32 and production of antioxidant molecules33, such as putrescine and spermidine, were also selected under antibiotic selection (Supplementary Data 3). In response to DNA-damaging antibiotic stress, populations mutated members of the SOS regulon ( dinB , yafO and yafP ) and cryptic prophages (cryptic prophage CP4-44).…”

Section: Resultsmentioning

confidence: 99%

Genome-wide analysis captures the determinants of the antibiotic cross-resistance interaction network

et al. 2014

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Understanding how evolution of antimicrobial resistance increases resistance to other drugs is a challenge of profound importance. By combining experimental evolution and genome sequencing of 63 laboratory-evolved lines, we charted a map of cross-resistance interactions between antibiotics in Escherichia coli, and explored the driving evolutionary principles. Here, we show that (1) convergent molecular evolution is prevalent across antibiotic treatments, (2) resistance conferring mutations simultaneously enhance sensitivity to many other drugs and (3) 27% of the accumulated mutations generate proteins with compromised activities, suggesting that antibiotic adaptation can partly be achieved without gain of novel function. By using knowledge on antibiotic properties, we examined the determinants of cross-resistance and identified chemogenomic profile similarity between antibiotics as the strongest predictor. In contrast, cross-resistance between two antibiotics is independent of whether they show synergistic effects in combination. These results have important implications on the development of novel antimicrobial strategies.

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“…Allen et al (25) have reported that reactive oxygen species (ROS), which are also known to damage DNA, proteins, and phospholipid membranes, accumulate in yeast cells during growth in the presence of furfural. In E. coli, polyamines protect DNA from damage by agents of oxidative stress (41,42). Overexpression of thyA, thymidylate synthase, has also been demonstrated to increase furfural resistance in E. coli (14) and may facilitate repair of furfural-damaged DNA.…”

Section: Discussionmentioning

confidence: 99%

“…Concentrations are maintained within a specific range (45) and elevated during exponential growth (46). Polyamines bind anionic structures such as plasma membranes, ribosomes, and DNA (42,47). This binding protects DNA from damage by some reactive compounds (41), regulates gene expression, and modulates translational fidelity (45,48).…”

Section: Discussionmentioning

confidence: 99%

Polyamine Transporters and Polyamines Increase Furfural Tolerance during Xylose Fermentation with Ethanologenic Escherichia coli Strain LY180

Geddes

Wang

Yomano

et al. 2014

Appl Environ Microbiol

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Expression of genes encoding polyamine transporters from plasmids and polyamine supplements increased furfural tolerance (growth and ethanol production) in ethanologenic Escherichia coli LY180 (in AM1 mineral salts medium containing xylose). This represents a new approach to increase furfural tolerance and may be useful for other organisms. Microarray comparisons of two furfural-resistant mutants (EMFR9 and EMFR35) provided initial evidence for the importance of polyamine transporters. Each mutant contained a single polyamine transporter gene that was upregulated over 100-fold (microarrays) compared to that in the parent LY180, as well as a mutation that silenced the expression of yqhD. Based on these genetic changes, furfural tolerance was substantially reconstructed in the parent, LY180. Deletion of potE in EMFR9 lowered furfural tolerance to that of the parent. Deletion of potE and puuP in LY180 also decreased furfural tolerance, indicating functional importance of the native genes. Of the 8 polyamine transporters (18 genes) cloned and tested, half were beneficial for furfural tolerance (PotE, PuuP, PlaP, and PotABCD). Supplementing AM1 mineral salts medium with individual polyamines (agmatine, putrescine, and cadaverine) also increased furfural tolerance but to a smaller extent. In pH-controlled fermentations, polyamine transporter plasmids were shown to promote the metabolism of furfural and substantially reduce the time required to complete xylose fermentation. This increase in furfural tolerance is proposed to result from polyamine binding to negatively charged cellular constituents such as nucleic acids and phospholipids, providing protection from damage by furfural.

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Polyamines reduce oxidative stress in Escherichia coli cells exposed to bactericidal antibiotics

Cited by 96 publications

References 26 publications

Putrescine Reduces Antibiotic-Induced Oxidative Stress as a Mechanism of Modulation of Antibiotic Resistance in Burkholderia cenocepacia

Putrescine Reduces Antibiotic-Induced Oxidative Stress as a Mechanism of Modulation of Antibiotic Resistance in Burkholderia cenocepacia

Genome-wide analysis captures the determinants of the antibiotic cross-resistance interaction network

Polyamine Transporters and Polyamines Increase Furfural Tolerance during Xylose Fermentation with Ethanologenic Escherichia coli Strain LY180

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