Skip to main content
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems
  • Log in
  • My alerts
  • My Cart

Main menu

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About AAC
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • AAC Podcast
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems

User menu

  • Log in
  • My alerts
  • My Cart

Search

  • Advanced search
Antimicrobial Agents and Chemotherapy
publisher-logosite-logo

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About AAC
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • AAC Podcast
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
Mechanisms of Action: Physiological Effects

Dimethyl Sulfoxide Protects Escherichia coli from Rapid Antimicrobial-Mediated Killing

Hongfei Mi, Dai Wang, Yunxin Xue, Zhi Zhang, Jianjun Niu, Yuzhi Hong, Karl Drlica, Xilin Zhao
Hongfei Mi
aState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiang-An District, Xiamen, Fujian Province, China
bSchool of Public Health, Fujian Medical University, Minhou District, Fuzhou, Fujian Province, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dai Wang
aState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiang-An District, Xiamen, Fujian Province, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yunxin Xue
aState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiang-An District, Xiamen, Fujian Province, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zhi Zhang
aState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiang-An District, Xiamen, Fujian Province, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jianjun Niu
aState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiang-An District, Xiamen, Fujian Province, China
bSchool of Public Health, Fujian Medical University, Minhou District, Fuzhou, Fujian Province, China
cZhongshan Hospital, Affiliated Hospital of Xiamen University Medical School, Siming District, Xiamen, Fujian Province, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yuzhi Hong
dPublic Health Research Institute and Department of Microbiology, Biochemistry, and Molecular Genetics, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Karl Drlica
dPublic Health Research Institute and Department of Microbiology, Biochemistry, and Molecular Genetics, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xilin Zhao
aState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiang-An District, Xiamen, Fujian Province, China
dPublic Health Research Institute and Department of Microbiology, Biochemistry, and Molecular Genetics, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1128/AAC.03003-15
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

ABSTRACT

The contribution of reactive oxygen species (ROS) to antimicrobial lethality was examined by treating Escherichia coli with dimethyl sulfoxide (DMSO), an antioxidant solvent frequently used in antimicrobial studies. DMSO inhibited killing by ampicillin, kanamycin, and two quinolones and had little effect on MICs. DMSO-mediated protection correlated with decreased ROS accumulation and provided evidence for ROS-mediated programmed cell death. These data support the contribution of ROS to antimicrobial lethality and suggest caution when using DMSO-dissolved antimicrobials for short-time killing assays.

TEXT

One approach to help stem the emergence of new antimicrobial resistance is to kill bacterial pathogens rapidly, thereby quickly reducing bacterial burden and restricting effects of stress-induced mutagenesis (1, 2). Reactive oxygen species (ROS) have been proposed to be key factors in antimicrobial lethality (3–5), and substantial evidence supports this proposition (3–19). However, their role in lethality has been challenged (20, 21). If ROS are indeed integral to antimicrobial-mediated killing, compounds that act as antioxidants and radical scavengers should reduce antimicrobial lethality. We chose to examine this hypothesis using the radical scavenger dimethyl sulfoxide (DMSO) (22, 23), because it is also a popular solvent that is widely used in the pharmaceutical industry and in antimicrobial research due to its (i) low toxicity, (ii) ability to dissolve both organic and inorganic compounds, (iii) ability to remain in a liquid state over a broad temperature range (e.g., from 19°C to 189°C), (iv) ability to enhance cell membrane permeability, and (v) miscibility in water and a wide range of organic solvents. We report here that DMSO interferes with rapid killing of Escherichia coli and Acinetobacter baumannii by members of three antimicrobial classes.

E. coli K-12 strains BW25113 and ATCC 25922 and A. baumannii strain ATCC 17978 were grown in Luria-Bertani (LB) broth or on LB agar at 37°C. LB medium, ampicillin, and kanamycin were obtained from Sangon Biotech Co., Ltd. (Shanghai, China). Oxolinic acid, ciprofloxacin, and DMSO were acquired from Sigma-Aldrich Co. (St. Louis, MO). Meropenem (Sumitomo Dainippon Pharma Co. Ltd.) was obtained from Zhongshan Hospital Pharmacy. The fluorescent probe carboxy-H2DCFDA [5(6)-carboxy-2′,7′-dichlorodihydrofluorescein diacetate] was purchased from Invitrogen (Grand Island, NY). All chemical stock solutions were dissolved in sterile water (except carboxy-H2DCFDA, which was dissolved in DMSO) and stored at −80°C until use. MICs were assayed by broth dilution according to CLSI protocols (24); exponentially growing cultures were diluted to 105 CFU/ml for MIC determinations. To measure rapid bacterial killing, exponentially growing cultures at about 5 × 108 CFU/ml were treated with antimicrobials, after which they were serially diluted and plated on drug-free agar. Viable colony counts were determined after an overnight incubation at 37°C; percentage survival rates were calculated relative to viable counts of samples taken immediately before antimicrobial addition. To measure intracellular ROS accumulation, a fluorescence dye, carboxy-H2DCFDA, was used. Carboxy-H2DCFDA readily penetrates E. coli cells (25, 26); once it enters cells, the compound is converted by cellular esterases into a membrane-impermeable cognate that can be oxidized to a fluorescent form by superoxide, hydrogen peroxide, or hydroxyl radicals (25). The fluorescent signal can then be analyzed by flow cytometry and fluorescence microscopy. E. coli cells were pretreated with 5 μM carboxy-H2DCFDA (1,000-fold dilution from 5 mM stock; DMSO carryover, 0.1%) for 10 min, followed by DMSO pretreatment for another 10 min before the addition of oxolinic acid (15× MIC, 9 μg/ml). After 150 min of oxolinic acid treatment, cells were washed with 1× phosphate-buffered saline (PBS) to remove the antimicrobial and extracellular carboxy-H2DCFDA, concentrated by centrifugation (17,000 × g for 1 min), and used to measure ROS levels by flow cytometry or fluorescence microscopy with a Beckman Coulter CyAn ADP analyzer or an Olympus BX43 microscope, respectively. Poststress programmed cell death was assessed by diluting exponentially growing cultures into LB liquid medium at 37°C to a cell density of 105 to 106 CFU/ml. Cells were then treated with 9 μg/ml oxolinic acid (15× MIC) for 90 min, and 200-μl samples were plated onto LB agar lacking or containing 7.5% (vol/vol) DMSO (one-half MIC). The ratio of the number of cells recovered from DMSO-containing agar to that of DMSO-free agar indicated the poststress programmed cell death.

We began by determining the MIC for DMSO, which was 15% (vol/vol). Subinhibitory DMSO concentrations (7.5% [one-half MIC] and 5% [one-third MIC]) had little effect on exponential growth of bacterial cultures (see Fig. S1 in the supplemental material) and no effect on the MIC of oxolinic acid, ciprofloxacin, or ampicillin; however, 5% and 7.5% DMSO each caused a 2-fold reduction in the kanamycin MIC (Table 1).

View this table:
  • View inline
  • View popup
TABLE 1

Effects of DMSO on antimicrobial-mediated growth inhibition

We next examined the effect of DMSO on rapid antimicrobial killing (minimal bactericidal concentration [MBC] was not measured, because it is insensitive to ROS [9, 11]). For quinolones (oxolinic acid and ciprofloxacin), coincubation with 5% or 7.5% DMSO suppressed lethality by 10- to 100-fold (Fig. 1A and B). The protective effect of DMSO was dose dependent in that decreasing the DMSO concentration also decreased the level of protection (Fig. 1C and D). Even at concentrations as low as 1%, a protective effect of DMSO was evident (Fig. 1C and D). As incubation time and drug concentration increased, the DMSO-mediated protective effect with oxolinic acid, a compound that depends mainly on ROS to kill bacteria (27), persisted, while that with ciprofloxacin, a compound that has both ROS-dependent and -independent modes of killing, gradually diminished (Fig. 2). At high concentrations of ciprofloxacin (Fig. 2E), DMSO showed no protective effect. These data support the idea that DMSO interferes with ROS-mediated lethality. In both cases, DMSO had no effect on MICs, which emphasizes the mechanistic difference between transient ROS-mediated killing and MICs.

FIG 1
  • Open in new tab
  • Download powerpoint
FIG 1

DMSO counteracts quinolone-mediated lethality. Exponentially growing E. coli BW25113 cells were treated with 9 μg/ml (15× MIC) oxolinic acid (Oxo) (A and C) or 0.048 μg/ml (2× MIC) ciprofloxacin (Cip) (B and D) for the indicated times (A and B) in the absence or presence of 5% or 7.5% DMSO. Cultures were also treated with 9 μg/ml (15× MIC) oxolinic acid for 2.5 h (C) or 0.048 μg/ml (2× MIC) ciprofloxacin for 4 h (D) in the presence of various concentrations of DMSO. Shown are the average values from experiments conducted at least three times. Error bars indicate deviations as standard errors of the mean.

FIG 2
  • Open in new tab
  • Download powerpoint
FIG 2

Increased incubation times and drug concentrations diminish DMSO-mediated protection from killing by ciprofloxacin but not by oxolinic acid. Exponentially growing cultures of E. coli strain BW25113 were treated with 9 μg/ml (15× MIC) oxolinic acid (Oxo) (A), 0.048 μg/ml (2× MIC) ciprofloxacin (B), or 0.24 μg/ml (10× MIC) ciprofloxacin (C) for the indicated times in the absence or presence of 5% or 7.5% DMSO. Cells were also treated with various concentrations of oxolinic acid for 2.5 h (D) or ciprofloxacin (E) for 75 min. The culture regrowth seen in the 24-h ciprofloxacin-only sample shown in panel B may have derived from selection of ciprofloxacin-resistant mutants at the low drug concentrations and long incubation times used. Shown are the average values from experiments conducted at least three times. Error bars indicate deviations as standard errors of the mean.

A similar protective effect of DMSO was also observed with two other classes of antimicrobials, ampicillin and kanamycin. With ampicillin, 7.5% DMSO reduced killing by about 100-fold, while 5% DMSO reduced it by about 10-fold (Fig. 3A); at 1% DMSO, ampicillin-mediated killing was reduced by 10-fold after 3 h of incubation (Fig. 3B). Since DMSO lowered the kanamycin MIC, we normalized the absolute kanamycin concentration to its MIC for killing measurements to separate static from lethal effects (28). At 4× MIC of kanamycin, DMSO reduced killing by up to 1,000-fold when incubation was for 30 min (Fig. 3C). At various concentrations of kanamycin (normalized to MIC), reductions in lethality were 5- to 100-fold at both 5% and 7.5% DMSO (Fig. 3D). It appears that 5% DMSO is saturating, since 7.5% DMSO conferred no more protection than did 5%, possibly because kanamycin triggers less ROS-mediated killing than quinolones and ampicillin. As with quinolones, increasing the incubation time and drug concentration to 24 h and 10× MIC, respectively, reduced the DMSO-mediated protective effects for both ampicillin and kanamycin (see Fig. S2 in the supplemental material). ROS-mediated killing may be masked by the antimicrobials exerting more direct lethality at longer exposure times and higher drug concentrations.

FIG 3
  • Open in new tab
  • Download powerpoint
FIG 3

DMSO counteracts ampicillin- and kanamycin-mediated lethality. Exponentially growing cultures of E. coli BW25113 were treated with 16 μg/ml (2× MIC) ampicillin (Amp) for various times in the absence or presence of 5% or 7.5% of DMSO (A), 16 μg/ml (2× MIC) ampicillin for 3 h in the presence of various concentrations of DMSO (B), 4× MIC of kanamycin (Kan) in the absence (24 μg/ml kanamycin) or presence (12 μg/ml kanamycin) of 5% or 7.5% DMSO for the indicated times (C), and various concentrations of kanamycin (normalized to the MIC) for 30 min in the absence or presence of 5% or 7.5% DMSO (D). Shown are the average values from experiments conducted at least three times. Error bars indicate deviations as standard errors of the mean.

To generalize our observations beyond applicability to a laboratory strain of E. coli, we next examined DMSO and antimicrobial lethality with two ATCC strains, ATCC 25922 (E. coli) and ATCC 17978 (A. baumannii). With these two strains, DMSO showed the greatest protection with quinolones, moderate protection with kanamycin, and little protection with β-lactams (Fig. 4). Thus, the DMSO-mediated protective effect does not appear to be limited to a specific bacterial strain or species.

FIG 4
  • Open in new tab
  • Download powerpoint
FIG 4

DMSO protects ATCC strains of E. coli and A. baumannii from antimicrobial-mediated lethality. Exponentially growing E. coli (ATCC 25922) (A, C, and E) or A. baumannii (ATCC 17978) (B, D, and F) cells were treated with 2× MIC of ciprofloxacin (Cip) (A and B), 2× MIC of kanamycin (Kan) (C and D), 20× MIC of ampicillin (Amp) (E), or 8× MIC of meropenem (Mero) (F) in the absence or presence of DMSO (one-half MIC, 5% for ATCC 25922 or 3% for ATCC 17978) for the indicated times. Shown are the average values from experiments conducted at least three times. Error bars indicate deviations as standard errors of the mean.

Since ROS have been implicated in bacterial death arising from a variety of stressors (3–6, 11) and since DMSO is reported to be an antioxidant that can scavenge hydroxyl radicals (22, 23), we examined the hypothesis that DMSO reduces antimicrobial-stimulated ROS accumulation. Intracellular ROS levels were measured by flow cytometry (Fig. 5A) and microscopy (Fig. 5B); both assays showed that coincubation with 7.5% DMSO reduced oxolinic acid-induced ROS accumulation. Thus, the ROS scavenging activity of DMSO (22, 23) appears to be involved in reducing rapid antimicrobial-mediated killing.

FIG 5
  • Open in new tab
  • Download powerpoint
FIG 5

DMSO reduces oxolinic acid-mediated intracellular ROS accumulation. Exponentially growing E. coli (BW25113) cultures were pretreated with 5 μM carboxy-H2DCFDA for 10 min, which was followed by DMSO pretreatment for another 10 min before cultures received oxolinic acid (15× MIC, 9 μg/ml) for 150 min. Samples taken immediately after and immediately before oxolinic acid treatment were washed once, resuspended in 1× phosphate-buffered saline, and subjected to flow cytometry (A) or microscopy (B). Red curve, untreated control; blue curve, DMSO pretreatment only; orange curve, oxolinic acid alone; green curve, oxolinic acid plus 7.5% DMSO. A.U., arbitrary units. Experiments in triplicate produced similar results.

We note that DMSO inhibits bacterial growth (MIC) through an ROS-unrelated mechanism, because (i) subinhibitory concentrations of hydrogen peroxide do not increase the DMSO MIC, and (ii) subinhibitory concentrations of other antioxidants (vitamin C and glutathione) do not reduce the DMSO MIC (data not shown). We speculate that DMSO inhibits growth via membrane perturbation; further work is required to establish the mechanism for growth inhibition.

We also examined DMSO for its effects on ROS-mediated antimicrobial-induced poststress programmed cell death (3). For this experiment, we treated an E. coli culture with 15× MIC oxolinic acid for 90 min and then plated the cells onto drug-free agar containing or lacking DMSO. DMSO in the agar reduced killing by 23-fold (Fig. 6), indicating that, at the time of plating, more than 95% of cells that would have been counted as dead on DMSO-free agar were still alive. After plating, these cells die from a poststress self-destructive process that involves ROS, since thiourea, another ROS scavenger, also protects bacteria from antimicrobial killing and antimicrobial-induced programmed cell death (3, 6, 9, 11). Collectively, these data are consistent with DMSO protecting from rapid antimicrobial-mediated killing through reduction of intracellular ROS levels.

FIG 6
  • Open in new tab
  • Download powerpoint
FIG 6

DMSO protects E. coli from stress-induced ROS-mediated programmed cell death. Exponentially growing cultures of E. coli BW25113 were serially diluted into prewarmed LB medium to a cell density of 105 to 106 CFU/ml. Cultures were then treated with 9 μg/ml oxolinic acid for 90 min, followed by immediate plating onto LB agar lacking or containing 7.5% (vol/vol) DMSO. The ratio of input cells (CFU) recovered from agar with DMSO to those without DMSO is indicated above paired columns. Shown are the average values from experiments conducted at least three times. Error bars indicate deviations as standard errors of the mean.

The interpretation of the effects of DMSO and other antioxidants (3, 7, 9, 11) and inhibitors of ROS accumulation (3, 9, 15) on antimicrobial lethality (21) is complicated by possible off-target effects of these compounds. However, the argument for the involvement of ROS in antimicrobial action is bolstered by both the present results and those obtained using complementary genetic and molecular approaches (6, 11, 15). Moreover, scavenging/blocking ROS accumulation is the common feature shared by a variety of diverse compounds (thiourea [3, 9, 11], bipyridyl [3, 9, 11], glutathione [9], vitamin C [7], and DMSO) that protect from antimicrobial killing, while off-target growth inhibitory effects of these compounds are less likely to derive from the same unspecified mechanisms. Another implication stemming from our study is that use of DMSO as a solvent for antimicrobials may need to be reconsidered because concentrations as low as 1% can reduce their efficacy, measured in the present case as rapid killing.

ACKNOWLEDGMENTS

We thank Marila Gennaro, Richard Pine, and Erika Shor for critical comments on our work. We also thank Wei Zhang for technical help with flow cytometry analysis.

This work was supported by the National Natural Science Foundation of China (grants 81473251, 81301474, and 31370166), the Natural Science Foundation of Fujian Province of China (grants 2014J01139 and 2015J01345), the Early-Stage Project of National Key Basic Research Program of China (grant 2014CB560710), the Open Research Fund of State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics (grant 2015001), and the National Institutes of Health (grants AI073491 and DP2OD007423).

We declare no conflicts of interest.

FOOTNOTES

    • Received 15 December 2015.
    • Returned for modification 2 January 2016.
    • Accepted 22 May 2016.
    • Accepted manuscript posted online 31 May 2016.
  • Supplemental material for this article may be found at http://dx.doi.org/10.1128/AAC.03003-15.

  • Copyright © 2016, American Society for Microbiology. All Rights Reserved.

REFERENCES

  1. 1.↵
    1. Malik M,
    2. Hoatam G,
    3. Chavda K,
    4. Kerns RJ,
    5. Drlica K
    . 2010. Novel approach for comparing the abilities of quinolones to restrict the emergence of resistant mutants during quinolone exposure. Antimicrob Agents Chemother 54:149–156. doi:10.1128/AAC.01035-09.
    OpenUrlAbstract/FREE Full Text
  2. 2.↵
    1. Stratton CW
    . 2003. Dead bugs don't mutate: susceptibility issues in the emergence of bacterial resistance. Emerg Infect Dis 9:10–16. doi:10.3201/eid0901.020172.
    OpenUrlCrossRefPubMedWeb of Science
  3. 3.↵
    1. Kohanski MA,
    2. Dwyer DJ,
    3. Hayete B,
    4. Lawrence CA,
    5. Collins JJ
    . 2007. A common mechanism of cellular death induced by bactericidal antibiotics. Cell 130:797–810. doi:10.1016/j.cell.2007.06.049.
    OpenUrlCrossRefPubMedWeb of Science
  4. 4.↵
    1. Zhao X,
    2. Drlica K
    . 2014. Reactive oxygen species and the bacterial response to lethal stress. Curr Opin Microbiol 21:1–6. doi:10.1016/j.mib.2014.06.008.
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Dwyer DJ,
    2. Collins JJ,
    3. Walker GC
    . 2015. Unraveling the physiological complexities of antibiotic lethality. Annu Rev Pharmacol Toxicol 55:313–332. doi:10.1146/annurev-pharmtox-010814-124712.
    OpenUrlCrossRef
  6. 6.↵
    1. Dorsey-Oresto A,
    2. Lu T,
    3. Mosel M,
    4. Wang X,
    5. Salz T,
    6. Drlica K,
    7. Zhao X
    . 2013. YihE kinase is a central regulator of programmed cell death in bacteria. Cell Rep 3:528–537. doi:10.1016/j.celrep.2013.01.026.
    OpenUrlCrossRefPubMedWeb of Science
  7. 7.↵
    1. Goswami M,
    2. Mangoli SH,
    3. Jawali N
    . 2006. Involvement of reactive oxygen species in the action of ciprofloxacin against Escherichia coli. Antimicrob Agents Chemother 50:949–954. doi:10.1128/AAC.50.3.949-954.2006.
    OpenUrlAbstract/FREE Full Text
  8. 8.↵
    1. Kohanski MA,
    2. Dwyer DJ,
    3. Collins JJ
    . 2010. How antibiotics kill bacteria: from targets to networks. Nat Rev Microbiol 8:423–435. doi:10.1038/nrmicro2333.
    OpenUrlCrossRefPubMedWeb of Science
  9. 9.↵
    1. Liu Y,
    2. Liu X,
    3. Qu Y,
    4. Wang X,
    5. Li L,
    6. Zhao X
    . 2012. Inhibitors of reactive oxygen species accumulation delay and/or reduce the lethality of several antistaphylococcal agents. Antimicrob Agents Chemother 56:6048–6050. doi:10.1128/AAC.00754-12.
    OpenUrlAbstract/FREE Full Text
  10. 10.↵
    1. Mosel M,
    2. Li L,
    3. Drlica K,
    4. Zhao X
    . 2013. Superoxide-mediated protection of Escherichia coli from antimicrobials. Antimicrob Agents Chemother 57:5755–5759. doi:10.1128/AAC.00754-13.
    OpenUrlAbstract/FREE Full Text
  11. 11.↵
    1. Wang X,
    2. Zhao X
    . 2009. Contribution of oxidative damage to antimicrobial lethality. Antimicrob Agents Chemother 53:1395–1402. doi:10.1128/AAC.01087-08.
    OpenUrlAbstract/FREE Full Text
  12. 12.↵
    1. Zhao X,
    2. Hong Y,
    3. Drlica K
    . 2015. Moving forward with reactive oxygen species involvement in antimicrobial lethality. J Antimicrob Chemother 70:639–642. doi:10.1093/jac/dku463.
    OpenUrlCrossRefPubMed
  13. 13.↵
    1. Burger RM,
    2. Drlica K
    . 2009. Superoxide protects Escherichia coli from bleomycin mediated lethality. J Inorg Biochem 103:1273–1277. doi:10.1016/j.jinorgbio.2009.07.009.
    OpenUrlCrossRefPubMed
  14. 14.↵
    1. Davies BW,
    2. Kohanski MA,
    3. Simmons LA,
    4. Winkler JA,
    5. Collins JJ,
    6. Walker GC
    . 2009. Hydroxyurea induces hydroxyl radical-mediated cell death in Escherichia coli. Mol Cell 36:845–860. doi:10.1016/j.molcel.2009.11.024.
    OpenUrlCrossRefPubMedWeb of Science
  15. 15.↵
    1. Dwyer DJ,
    2. Belenky P,
    3. Yang JH,
    4. MacDonald IC,
    5. Martell JD,
    6. Takahashi N,
    7. Chan CTY,
    8. Lobritz MA,
    9. Braff D,
    10. Schwarz EG,
    11. Ye JD,
    12. Pati M,
    13. Vercruysse M,
    14. Ralifo PS,
    15. Allison KR,
    16. Khalil AS,
    17. Ting AY,
    18. Walker GC,
    19. Collins JJ
    . 2014. Antibiotics induce redox-related physiological alterations as part of their lethality. Proc Natl Acad Sci U S A 111:E2100–E2109. doi:10.1073/pnas.1401876111.
    OpenUrlAbstract/FREE Full Text
  16. 16.↵
    1. Dwyer DJ,
    2. Kohanski MA,
    3. Hayete B,
    4. Collins JJ
    . 2007. Gyrase inhibitors induce an oxidative damage cellular death pathway in Escherichia coli. Mol Syst Biol 3:91. doi:10.1038/msb4100135.
    OpenUrlCrossRefPubMed
  17. 17.↵
    1. Foti JJ,
    2. Devadoss B,
    3. Winkler JA,
    4. Collins JJ,
    5. Walker GC
    . 2012. Oxidation of the guanine nucleotide pool underlies cell death by bactericidal antibiotics. Science 336:315–319. doi:10.1126/science.1219192.
    OpenUrlAbstract/FREE Full Text
  18. 18.↵
    1. Dong TG,
    2. Dong S,
    3. Catalano C,
    4. Moore R,
    5. Liang X,
    6. Mekalanos JJ
    . 2015. Generation of reactive oxygen species by lethal attacks from competing microbes. Proc Natl Acad Sci U S A 112:2181–2186. doi:10.1073/pnas.1425007112.
    OpenUrlAbstract/FREE Full Text
  19. 19.↵
    1. Li L,
    2. Hong Y,
    3. Luan G,
    4. Mosel M,
    5. Malik M,
    6. Drlica K,
    7. Zhao X
    . 2014. Ribosomal elongation factor 4 promotes cell death associated with lethal stress. mBio 5:e01708. doi:10.1128/mBio.01708-14.
    OpenUrlCrossRefPubMed
  20. 20.↵
    1. Keren I,
    2. Wu Y,
    3. Inocencio J,
    4. Mulcahy LR,
    5. Lewis K
    . 2013. Killing by bactericidal antibiotics does not depend on reactive oxygen species. Science 339:1213–1216. doi:10.1126/science.1232688.
    OpenUrlAbstract/FREE Full Text
  21. 21.↵
    1. Liu Y,
    2. Imlay JA
    . 2013. Cell death from antibiotics without the involvement of reactive oxygen species. Science 339:1210–1213. doi:10.1126/science.1232751.
    OpenUrlAbstract/FREE Full Text
  22. 22.↵
    1. Repine JE,
    2. Pfenninger OW,
    3. Talmage DW,
    4. Berger EM,
    5. Pettijohn DE
    . 1981. Dimethyl sulfoxide prevents DNA nicking mediated by ionizing radiation or iron/hydrogen peroxide-generated hydroxyl radical. Proc Natl Acad Sci U S A 78:1001–1003. doi:10.1073/pnas.78.2.1001.
    OpenUrlAbstract/FREE Full Text
  23. 23.↵
    1. Dabrowski A,
    2. Gabryelewicz A,
    3. Dabrowska M,
    4. Chyczewski L
    . 1991. Effect of dimethylsulfoxide-hydroxyl radical scavenger on cerulein-induced acute pancreatitis in rats. Tokai J Exp Clin Med 16:43–50.
    OpenUrlPubMed
  24. 24.↵
    CLSI. 2009. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: approved standard. CLSI document M07-A8, vol 29, no. 2. CLSI, Wayne, PA.
  25. 25.↵
    1. Bass DA,
    2. Parce JW,
    3. Dechatelet LR,
    4. Szejda P,
    5. Seeds MC,
    6. Thomas M
    . 1983. Flow cytometric studies of oxidative product formation by neutrophils: a graded response to membrane stimulation. J Immunol 130:1910–1917.
    OpenUrlAbstract
  26. 26.↵
    1. Brandt R,
    2. Keston AS
    . 1965. Synthesis of diacetyldichlorofluorescin: a stable reagent for fluorometric analysis. Anal Biochem 11:6–9. doi:10.1016/0003-2697(65)90035-7.
    OpenUrlCrossRefPubMedWeb of Science
  27. 27.↵
    1. Wang X,
    2. Zhao X,
    3. Malik M,
    4. Drlica K
    . 2010. Contribution of reactive oxygen species to pathways of quinolone-mediated bacterial cell death. J Antimicrob Chemother 65:520–524. doi:10.1093/jac/dkp486.
    OpenUrlCrossRefPubMedWeb of Science
  28. 28.↵
    1. Zhao X,
    2. Hong Y,
    3. Drlica K
    . 2015. Moving forward with reactive oxygen species involvement in antimicrobial lethality. J Antimicrob Chemother 70:639–642. doi:10.1093/jac/dku463.
    OpenUrlCrossRefPubMed
View Abstract
PreviousNext
Back to top
Download PDF
Citation Tools
Dimethyl Sulfoxide Protects Escherichia coli from Rapid Antimicrobial-Mediated Killing
Hongfei Mi, Dai Wang, Yunxin Xue, Zhi Zhang, Jianjun Niu, Yuzhi Hong, Karl Drlica, Xilin Zhao
Antimicrobial Agents and Chemotherapy Jul 2016, 60 (8) 5054-5058; DOI: 10.1128/AAC.03003-15

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Print

Alerts
Sign In to Email Alerts with your Email Address
Email

Thank you for sharing this Antimicrobial Agents and Chemotherapy article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Dimethyl Sulfoxide Protects Escherichia coli from Rapid Antimicrobial-Mediated Killing
(Your Name) has forwarded a page to you from Antimicrobial Agents and Chemotherapy
(Your Name) thought you would be interested in this article in Antimicrobial Agents and Chemotherapy.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Dimethyl Sulfoxide Protects Escherichia coli from Rapid Antimicrobial-Mediated Killing
Hongfei Mi, Dai Wang, Yunxin Xue, Zhi Zhang, Jianjun Niu, Yuzhi Hong, Karl Drlica, Xilin Zhao
Antimicrobial Agents and Chemotherapy Jul 2016, 60 (8) 5054-5058; DOI: 10.1128/AAC.03003-15
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • ABSTRACT
    • TEXT
    • ACKNOWLEDGMENTS
    • FOOTNOTES
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

Related Articles

Cited By...

About

  • About AAC
  • Editor in Chief
  • Editorial Board
  • Policies
  • For Reviewers
  • For the Media
  • For Librarians
  • For Advertisers
  • Alerts
  • AAC Podcast
  • RSS
  • FAQ
  • Permissions
  • Journal Announcements

Authors

  • ASM Author Center
  • Submit a Manuscript
  • Article Types
  • Ethics
  • Contact Us

Follow #AACJournal

@ASMicrobiology

       

ASM Journals

ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology.

About ASM | Contact Us | Press Room

 

ASM is a member of

Scientific Society Publisher Alliance

 

American Society for Microbiology
1752 N St. NW
Washington, DC 20036
Phone: (202) 737-3600

Copyright © 2021 American Society for Microbiology | Privacy Policy | Website feedback

Print ISSN: 0066-4804; Online ISSN: 1098-6596