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Clinical Therapeutics

Antibiotic-Mediated Modulations of Outer Membrane Vesicles in Enterohemorrhagic Escherichia coli O104:H4 and O157:H7

Andreas Bauwens, Lisa Kunsmann, Helge Karch, Alexander Mellmann, Martina Bielaszewska
Andreas Bauwens
aInstitute for Hygiene, University of Münster, Münster, Germany
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Lisa Kunsmann
aInstitute for Hygiene, University of Münster, Münster, Germany
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Helge Karch
aInstitute for Hygiene, University of Münster, Münster, Germany
bInterdisciplinary Center for Clinical Research (IZKF), University of Münster, Münster, Germany
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Alexander Mellmann
aInstitute for Hygiene, University of Münster, Münster, Germany
bInterdisciplinary Center for Clinical Research (IZKF), University of Münster, Münster, Germany
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  • ORCID record for Alexander Mellmann
Martina Bielaszewska
aInstitute for Hygiene, University of Münster, Münster, Germany
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DOI: 10.1128/AAC.00937-17
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ABSTRACT

Ciprofloxacin, meropenem, fosfomycin, and polymyxin B strongly increase production of outer membrane vesicles (OMVs) in Escherichia coli O104:H4 and O157:H7. Ciprofloxacin also upregulates OMV-associated Shiga toxin 2a, the major virulence factor of these pathogens, whereas the other antibiotics increase OMV production without the toxin. These two effects might worsen the clinical outcome of infections caused by Shiga toxin-producing E. coli. Our data support the existing recommendations to avoid antibiotics for treatment of these infections.

TEXT

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes most EHEC infections worldwide (1), but the most severe EHEC outbreak, with a high progression rate of infection to life-threatening hemolytic uremic syndrome (HUS), was caused in 2011 by E. coli O104:H4 (2), which is a hybrid of EHEC and enteroaggregative E. coli (3, 4). Both of these pathogens secrete subsets of their virulence factors, including Shiga toxin (Stx) 2a, the major EHEC virulence molecule, via outer membrane vesicles (OMVs) released during growth (5, 6). Since certain antibiotics increase Stx production (7–9), which may increase the risk of HUS development in patients treated with antibiotics during the initial phase of diarrhea (10–13), antibiotics are not recommended for treatment of EHEC infections (10–15). However, therapeutic or prophylactic administration of antibiotics was necessary in some patients during the E. coli O104:H4 outbreak (16–18). In our previous study, we identified several antibiotics potentially useful for treatment of E. coli O104:H4-infected patients based on their failure to induce stx2a-harboring bacteriophages and increase total Stx2a production in the outbreak strain (16). However, it is unknown if these antibiotics affect production of OMVs and OMV-associated Stx2a. Here, we determined effects of several antibiotics, including those used during the 2011 outbreak, on OMV production, the amount of OMV-associated Stx2a, and degree of OMV cytotoxicity in EHEC O104:H4 and EHEC O157:H7 (the most common EHEC serotype associated with severe disease) (1, 14).

MICs of the antibiotics used (Table 1) for EHEC O104:H4 outbreak isolate LB226692 (3, 4) and EHEC O157:H7 strain 5791/99 (6) were determined according to the guidelines of the Clinical and Laboratory Standards Institute (19), as described previously (16). To test effects of the antibiotics on the production of OMVs, the amount of OMV-associated Stx2a, and degree of OMV cytotoxicity, the strains were grown until an optical density at 600 nm (OD600) of 0.5 was reached. Aliquots of 150 ml were then supplemented with 1/4 MIC of each antibiotic or with 0.5 μg/ml of mitomycin C (positive control) (20, 21) or left untreated (negative control) and then cultured for 16 h. OMVs were isolated by ultracentrifugation of sterile-filtered supernatants (5, 6) and resuspended in 1 ml of 20 mM Tris-HCl (pH 8.0); numbers of CFU/ml were determined by a standard plate dilution method. OMVs and OMV-associated Stx2a were quantified by immunoblot of OMV preparations (10 μl/lane) with antibodies against the outer membrane protein A (OmpA) (an OMV marker) and Stx2a, respectively (6), and the densitometric signals were normalized to CFU/ml. OMV cytotoxicity titers were determined by Vero cell assay (5). The amounts of OMVs and OMV-associated Stx2a and degree of OMV cytotoxicity produced in the presence of each antibiotic was expressed as a fold increase of that produced by untreated bacteria. Total OMV protein concentrations were determined by Roti-Nanoquant (Carl Roth) and normalized to CFU/ml. The total OMV protein content in the presence of each antibiotic was expressed as a fold increase of that in the absence of antibiotics.

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TABLE 1

MICs of the antibiotics used for EHEC O104:H4 and O157:H7

The antibiotics differentially modulated OMV and OMV-Stx2a production and OMV cytotoxicity in strains LB226692 and 5791/99 (Fig. 1). Ciprofloxacin strongly increased production of OMVs (250-fold and 183-fold) and OMV-associated Stx2a (143-fold and 123-fold) and increased OMV cytotoxicity (1024-fold and 512-fold) in the respective strains. Similar effects were elicited by mitomycin C, which increased OMV production (568-fold and 470-fold, respectively), OMV-associated Stx2a (332-fold and 275-fold, respectively), and OMV cytotoxicity (1,024-fold). Fosfomycin also increased OMV production in each strain (77-fold and 24-fold, respectively), as did meropenem (27-fold and 14-fold, respectively) and polymyxin B (9-fold and 7-fold, respectively). However, none of the last three antibiotics affected the amount of OMV-associated Stx2a and OMV cytotoxicity in any of the strains. Gentamicin, rifaximin, tigecycline, and azithromycin did not influence OMV production in any strain but differentially modulated OMV-associated Stx2a and, thus, OMV cytotoxicity. Specifically, in strain LB226692, rifaximin, tigecycline, and azithromycin significantly reduced OMV-associated Stx2a and OMV cytotoxicity, whereas these antibiotics had no effects on these characteristics in strain 5791/99. No changes in OMV production, but significant decreases of OMV-associated Stx2a and OMV cytotoxicity, were elicited in both strains by chloramphenicol (Fig. 1). The upregulations of OMV production by ciprofloxacin, fosfomycin, meropenem, polymyxin B, and mitomycin C determined by immunoblot with anti-OmpA antibody (Fig. 1) were confirmed in each strain by quantifying the total OMV protein contents (Table 2).

FIG 1
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FIG 1

Effects of antibiotics on the production of OMVs, OMV-associated Stx2a, and OMV cytotoxicity in EHEC O104:H4 and O157:H7. Strains LB226692 (O104:H4) (A) and 5791/99 (O157:H7) (B) were grown for 16 h in the presence of 1/4 MIC of ciprofloxacin (CIP), fosfomycin (FOF), meropenem (MEM), polymyxin B (PMB), gentamicin (GEN), rifaximin (RIF), tigecycline (TGC), azithromycin (AZM), or chloramphenicol (CHL), 0.5 μg/ml of mitomycin C (MMC) (positive control), or without antibiotics (negative control). OMVs and OMV-associated Stx2a were quantified by immunoblot with anti-OmpA and anti-Stx2a antibodies, respectively, and normalized to CFU/ml. OMV cytotoxicity was determined by Vero cell assay. The data show a fold increase in each respective characteristic in the presence of the indicated antibiotic compared to untreated culture (set up as 1.0), and are expressed as means ± standard deviations from three independent experiments. *, P < 0.05; **, P < 0.01; and ***, P < 0.001 (one-sample t test with P value adjustments for multiple comparisons by Benjamini–Hochberg method).

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TABLE 2

Modulation of OMV production in EHEC O104:H4 and O157:H7 by antibiotics and mitomycin C determined by quantification of total OMV protein contents

We demonstrate for the first time that particular antibiotics significantly upregulate OMV production in EHEC O104:H4 and O157:H7. These effects on vesiculation occur together with or without modulation of OMV-associated Stx2a. This plausibly reflects different mechanisms involved in OMV and OMV-Stx2a production and different abilities of the particular antibiotics to interfere with these mechanisms. Specifically, the upregulation of EHEC vesiculation by the SOS response inducers ciprofloxacin and mitomycin C (21, 22) is consistent with the involvement of the SOS response in ciprofloxacin-mediated increase of OMV production in Pseudomonas aeruginosa (22) and in mitomycin C-mediated increase of vesiculation in Shigella dysenteriae type 1 (20). Since the SOS responses triggered by ciprofloxacin and mitomycin C also lead to induction of stx2a-harboring bacteriophages (9, 16, 21), the OMV upregulation is accompanied by upregulation of OMV-associated Stx2a and, thus, OMV cytotoxicity after exposure to these agents. In contrast, fosfomycin, meropenem, and polymyxin B plausibly increase OMV production by acting as envelope stressors (9, 23, 24). The increase of EHEC OMV production by these antibiotics is in agreement with similar effects reported for meropenem in P. aeruginosa (25), for imipenem (another carbapenem) in Stenotrophomonas maltophilia (24), and for polymyxin B in non-EHEC E. coli (23) and P. aeruginosa (26). However, the failures of fosfomycin, meropenem, and polymyxin B to induce stx2a-harboring phages and increase Stx production (8, 9, 16) result in an exclusive increase of OMVs without OMV-associated Stx2a. Altogether, our observations of OMV upregulation by antibiotics which induce the SOS response or act as envelope stressors are in agreement with the identification of OMV production as a novel type of bacterial stress response (22, 23, 26, 27). In general, our data support the recommendations to avoid antibiotics for treatment of EHEC infections (10–15). Specifically, the observation that ciprofloxacin strongly upregulates the OMV-associated Stx2a, which is toxic to human glomerular and brain microvascular endothelial cells (6), the major targets during HUS (14, 28), confirms that administration of ciprofloxacin may enhance the risk of HUS development. Furthermore, EHEC O104:H4 OMVs induce, via their non-Stx2a components (lipopolysaccharide and flagellin), secretion of interleukin 8 (5), one of the proinflammatory cytokines involved in the pathogenesis of HUS (14, 28). Thus, even increased OMV production itself without Stx2a upregulation, as observed for fosfomycin, meropenem, and polymyxin B, might worsen the clinical outcome of an EHEC infection. Although administration of fosfomycin was not associated with an increased risk of HUS development (29), the upregulation of OMV production by this antibiotic shown for the first time in our study warrants caution in its use for treatment of EHEC-infected patients. In contrast to the other antibiotics, inhibitors of protein synthesis did not upregulate OMVs or OMV-associated Stx2a in EHEC O104:H4 and O157:H7. Thus, these agents, particularly rifaximin and azithromycin, which were used during the 2011 EHEC O104:H4 outbreak (17, 18), might be considered options if antibiotic therapy of EHEC-infected patients is inevitable.

ACKNOWLEDGMENTS

This study was supported by grants from the EU FP7 ANTIGONE (278976), the Deutsche Forschungsgemeinschaft (DFG) Sonderforschungsbereich (SFB) 1009 (project B04), and the Interdisciplinary Center for Clinical Research (IZKF) Münster (Me2/010/16). The funders had no role in study design, data collection or interpretation, or the decision to submit the work for publication.

We thank Roland Lloubes (Laboratoire d'Ingénierie des Systèmes Macromoléculaires UMR7255, CNRS-Aix-Marseille Université, France) and Xiaohua He (Western Regional Research Center, Agricultural Research Service, USDA, Albany, CA, USA) for providing us with antibodies against OmpA and Stx2a, respectively, Ivan Kouzel (Institute for Hygiene, University of Münster) for assistance with statistical analyses, and Evgeny A. Idelevich (Institute of Microbiology, University of Münster) and Phillip I. Tarr (Washington University School of Medicine, St. Louis, MO, USA) for fruitful discussions. The technical assistance of Nadine Brandt and Margarete Junge is greatly appreciated.

M.B., A.B., and A.M. designed the study; A.B., L.K., and M.B. performed experiments; M.B and A.B analyzed data; H.K. and A.M. supervised the study and raised funding; M.B. wrote the manuscript; and all authors edited and approved the final version.

The authors declare no conflict of interest.

FOOTNOTES

    • Received 3 May 2017.
    • Returned for modification 29 May 2017.
    • Accepted 9 June 2017.
    • Accepted manuscript posted online 12 June 2017.
  • Copyright © 2017 American Society for Microbiology.

All Rights Reserved .

REFERENCES

  1. 1.↵
    1. Karch H,
    2. Tarr PI,
    3. Bielaszewska M
    . 2005. Enterohaemorrhagic Escherichia coli in human medicine. Int J Med Microbiol295:405–418. doi:10.1016/j.ijmm.2005.06.009.
    OpenUrlCrossRefPubMedWeb of Science
  2. 2.↵
    1. Frank C,
    2. Werber D,
    3. Cramer JP,
    4. Askar M,
    5. Faber M,
    6. an der Heiden M,
    7. Bernard H,
    8. Fruth A,
    9. Prager R,
    10. Spode A,
    11. Wadl M,
    12. Zoufaly A,
    13. Jordan S,
    14. Kemper MJ,
    15. Follin P,
    16. Müller L,
    17. King LA,
    18. Rosner B,
    19. Buchholz U,
    20. Stark K,
    21. Krause G,
    22. Investigation Team HUS
    . 2011. Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany. N Engl J Med365:1771–1780. doi:10.1056/NEJMoa1106483.
    OpenUrlCrossRefPubMedWeb of Science
  3. 3.↵
    1. Bielaszewska M,
    2. Mellmann A,
    3. Zhang W,
    4. Köck R,
    5. Fruth A,
    6. Bauwens A,
    7. Peters G,
    8. Karch H
    . 2011. Characterisation of the Escherichia coli strain associated with an outbreak of haemolytic uraemic syndrome in Germany, 2011: a microbiological study. Lancet Infect Dis11:671–676. doi:10.1016/S1473-3099(11)70165-7.
    OpenUrlCrossRefPubMedWeb of Science
  4. 4.↵
    1. Mellmann A,
    2. Harmsen D,
    3. Cummings CA,
    4. Zentz EB,
    5. Leopold SR,
    6. Rico A,
    7. Prior K,
    8. Szczepanowski R,
    9. Ji Y,
    10. Zhang W,
    11. McLaughlin SF,
    12. Henkhaus JK,
    13. Leopold B,
    14. Bielaszewska M,
    15. Prager R,
    16. Brzoska PM,
    17. Moore RL,
    18. Guenther S,
    19. Rothberg JM,
    20. Karch H
    . 2011. Prospective genomic characterization of the German enterohemorrhagic Escherichia coli O104:H4 outbreak by rapid next generation sequencing technology. PLoS One6:e22751. doi:10.1371/journal.pone.0022751.
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Kunsmann L,
    2. Rüter C,
    3. Bauwens A,
    4. Greune L,
    5. Glüder M,
    6. Kemper B,
    7. Fruth A,
    8. Wai SN,
    9. He X,
    10. Lloubes R,
    11. Schmidt MA,
    12. Dobrindt U,
    13. Mellmann A,
    14. Karch H,
    15. Bielaszewska M
    . 2015. Virulence from vesicles: novel mechanisms of host cell injury by Escherichia coli O104:H4 outbreak strain. Sci Rep5:13252. doi:10.1038/srep13252.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Bielaszewska M,
    2. Rüter C,
    3. Bauwens A,
    4. Greune L,
    5. Jarosch KA,
    6. Steil D,
    7. Zhang W,
    8. He X,
    9. Lloubes R,
    10. Fruth A,
    11. Kim KS,
    12. Schmidt MA,
    13. Dobrindt U,
    14. Mellmann A,
    15. Karch H
    . 2017. Host cell interactions of outer membrane vesicle-associated virulence factors of enterohemorrhagic Escherichia coli O157: intracellular delivery, trafficking and mechanisms of cell injury. PLoS Pathog13(2):e1006159. doi:10.1371/journal.ppat.1006159.
    OpenUrlCrossRef
  7. 7.↵
    1. Grif K,
    2. Dierich MP,
    3. Karch H,
    4. Allerberger F
    . 1998. Strain-specific differences in the amount of Shiga toxin released from enterohemorrhagic Escherichia coli O157 following exposure to subinhibitory concentrations of antimicrobial agents. Eur J Clin Microbiol Infect Dis17:761–766. doi:10.1007/s100960050181.
    OpenUrlCrossRefPubMedWeb of Science
  8. 8.↵
    1. Kimmitt PT,
    2. Harwood CR,
    3. Barer MR
    . 2000. Toxin gene expression by Shiga toxin-producing Escherichia coli: the role of antibiotics and the bacterial SOS response. Emerg Infect Dis6:458–465. doi:10.3201/eid0605.000503.
    OpenUrlCrossRefPubMedWeb of Science
  9. 9.↵
    1. Zhang X,
    2. McDaniel AD,
    3. Wolf LE,
    4. Keusch GT,
    5. Waldor MK,
    6. Acheson DW
    . 2000. Quinolone antibiotics induce Shiga toxin-encoding bacteriophages, toxin production, and death in mice. J Infect Dis181:664–670. doi:10.1086/315239.
    OpenUrlCrossRefPubMedWeb of Science
  10. 10.↵
    1. Wong CS,
    2. Jelacic S,
    3. Habeeb RL,
    4. Watkins SL,
    5. Tarr PI
    . 2000. The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med342:1930–1936. doi:10.1056/NEJM200006293422601.
    OpenUrlCrossRefPubMedWeb of Science
  11. 11.↵
    1. Smith KE,
    2. Wilker PR,
    3. Reiter PL,
    4. Hedican EB,
    5. Bender JB,
    6. Hedberg CW
    . 2012. Antibiotic treatment of Escherichia coli O157 infection and the risk of hemolytic uremic syndrome, Minnesota. Pediatr Infect Dis J31:37–41. doi:10.1097/INF.0b013e31823096a8.
    OpenUrlCrossRefPubMed
  12. 12.↵
    1. Freedman SB,
    2. Xie J,
    3. Neufeld MS,
    4. Hamilton WL,
    5. Hartling L,
    6. Tarr PI
    ,Alberta Provincial Pediatric Enteric Infection Team (APPETITE). 2016. Shiga toxin-producing Escherichia coli infection, antibiotics, and risk of developing hemolytic uremic syndrome: a meta-analysis. Clin Infect Dis62:1251–1258. doi:10.1093/cid/ciw099.
    OpenUrlCrossRefPubMed
  13. 13.↵
    1. Launders N,
    2. Byrne L,
    3. Jenkins C,
    4. Harker K,
    5. Charlett A,
    6. Adak GK
    . 2016. Disease severity of Shiga toxin-producing E. coli O157 and factors influencing the development of typical haemolytic uraemic syndrome: a retrospective cohort study, 2009-2012. BMJ Open6(1):e009933. doi:10.1136/bmjopen-2015-009933.
    OpenUrlAbstract/FREE Full Text
  14. 14.↵
    1. Tarr PI,
    2. Gordon CA,
    3. Chandler WL
    . 2005. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet365:1073–1086. doi:10.1016/S0140-6736(05)71144-2.
    OpenUrlCrossRefPubMedWeb of Science
  15. 15.↵
    1. Holtz LR,
    2. Neill MA,
    3. Tarr PI
    . 2009. Acute bloody diarrhea: a medical emergency for patients of all ages. Gastroenterology136:1887–1898. doi:10.1053/j.gastro.2009.02.059.
    OpenUrlCrossRefPubMedWeb of Science
  16. 16.↵
    1. Bielaszewska M,
    2. Idelevich EA,
    3. Zhang W,
    4. Bauwens A,
    5. Schaumburg F,
    6. Mellmann A,
    7. Peters G,
    8. Karch H
    . 2012. Effects of antibiotics on Shiga toxin 2 production and bacteriophage induction by epidemic Escherichia coli O104:H4 strain. Antimicrob Agents Chemother56:3277–3282. doi:10.1128/AAC.06315-11.
    OpenUrlAbstract/FREE Full Text
  17. 17.↵
    1. Menne J,
    2. Nitschke M,
    3. Stingele R,
    4. Abu-Tair M,
    5. Beneke J,
    6. Bramstedt J,
    7. Bremer JP,
    8. Brunkhorst R,
    9. Busch V,
    10. Dengler R,
    11. Deuschl G,
    12. Fellermann K,
    13. Fickenscher H,
    14. Gerigk C,
    15. Goettsche A,
    16. Greeve J,
    17. Hafer C,
    18. Hagenmüller F,
    19. Haller H,
    20. Herget-Rosenthal S,
    21. Hertenstein B,
    22. Hofmann C,
    23. Lang M,
    24. Kielstein JT,
    25. Klostermeier UC,
    26. Knobloch J,
    27. Kuehbacher M,
    28. Kunzendorf U,
    29. Lehnert H,
    30. Manns MP,
    31. Menne TF,
    32. Meyer TN,
    33. Michael C,
    34. Münte T,
    35. Neumann-Grutzeck C,
    36. Nuernberger J,
    37. Pavenstaedt H,
    38. Ramazan L,
    39. Renders L,
    40. Repenthin J,
    41. Ries W,
    42. Rohr A,
    43. Rump LC,
    44. Samuelsson O,
    45. Sayk F,
    46. Schmidt BM,
    47. Schnatter S,
    48. Schöcklmann H,
    49. Schreiber S,
    50. von Seydewitz CU,
    51. Steinhoff J,
    52. Stracke S,
    53. Suerbaum S,
    54. van de Loo A,
    55. Vischedyk M,
    56. Weissenborn K,
    57. Wellhöner P,
    58. Wiesner M,
    59. Zeissig S,
    60. Büning J,
    61. Schiffer M,
    62. Kuehbacher T
    ,EHEC-HUS consortium. 2012. Validation of treatment strategies for enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome: case-control study. BMJ345:e4565. doi:10.1136/bmj.e4565.
    OpenUrlAbstract/FREE Full Text
  18. 18.↵
    1. Vonberg RP,
    2. Höhle M,
    3. Aepfelbacher M,
    4. Bange FC,
    5. Belmar Campos C,
    6. Claussen K,
    7. Christner M,
    8. Cramer JP,
    9. Haller H,
    10. Hornef M,
    11. Fickenscher H,
    12. Fraedrich K,
    13. Knobloch JK,
    14. Kühbacher T,
    15. Manns MP,
    16. Nitschke M,
    17. Peters G,
    18. Pulz M,
    19. Rohde H,
    20. Roseland RT,
    21. Sayk F,
    22. Schaumburg F,
    23. Schöcklmann HO,
    24. Schubert S,
    25. Solbach W,
    26. Karch H,
    27. Suerbaum S
    . 2013. Duration of fecal shedding of Shiga toxin-producing Escherichia coli O104:H4 in patients infected during the 2011 outbreak in Germany: a multicenter study. Clin Infect Dis56:1132–1140. doi:10.1093/cid/cis1218.
    OpenUrlCrossRefPubMed
  19. 19.↵
    Clinical and Laboratory Standards Institute. 2009. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard,8th ed. CLSI document M07-A8. Clinical and Laboratory Standards Institute,Wayne, PA.
  20. 20.↵
    1. Dutta S,
    2. Iida K,
    3. Takade A,
    4. Meno Y,
    5. Nair GB,
    6. Yoshida S
    . 2004. Release of Shiga toxin by membrane vesicles in Shigella dysenteriae serotype 1 strains and in vitro effects of antimicrobials on toxin production and release. Microbiol Immunol48:965–969. doi:10.1111/j.1348-0421.2004.tb03626.x.
    OpenUrlCrossRefPubMed
  21. 21.↵
    1. Mühldorfer I,
    2. Hacker J,
    3. Keusch GT,
    4. Acheson DW,
    5. Tschäpe H,
    6. Kane AV,
    7. Ritter A,
    8. Olschläger T,
    9. Donohue-Rolfe A
    . 1996. Regulation of the Shiga-like toxin II operon in Escherichia coli. Infect Immun64:495–502.
    OpenUrlAbstract/FREE Full Text
  22. 22.↵
    1. Maredia R,
    2. Devineni N,
    3. Lentz P,
    4. Dallo SF,
    5. Yu J,
    6. Guentzel N,
    7. Chambers J,
    8. Arulanandam B,
    9. Haskins WE,
    10. Weitao T
    . 2012. Vesiculation from Pseudomonas aeruginosa under SOS. Scientific World J2012:402919. doi:10.1100/2012/402919.
    OpenUrlCrossRefPubMed
  23. 23.↵
    1. Manning AJ,
    2. Kuehn MJ
    . 2011. Contribution of bacterial outer membrane vesicles to innate bacterial defense. BMC Microbiol11:258. doi:10.1186/1471-2180-11-258.
    OpenUrlCrossRefPubMed
  24. 24.↵
    1. Devos S,
    2. Van Oudenhove L,
    3. Stremersch S,
    4. Van Putte W,
    5. De Rycke R,
    6. Van Driessche G,
    7. Vitse J,
    8. Raemdonck K,
    9. Devreese B
    . 2015. The effect of imipenem and diffusible signaling factors on the secretion of outer membrane vesicles and associated Ax21 proteins in Stenotrophomonas maltophilia. Front Microbiol6:298. doi:10.3389/fmicb.2015.00298.
    OpenUrlCrossRefPubMed
  25. 25.↵
    1. Siqueira VL,
    2. Cardoso RF,
    3. Caleffi-Ferracioli KR,
    4. Scodro RB,
    5. Fernandez MA,
    6. Fiorini A,
    7. Ueda-Nakamura T,
    8. Dias-Filho BP,
    9. Nakamura CV
    . 2014. Structural changes and differentially expressed genes in Pseudomonas aeruginosa exposed to meropenem-ciprofloxacin combination. Antimicrob Agents Chemother58:3957–3967. doi:10.1128/AAC.02584-13.
    OpenUrlAbstract/FREE Full Text
  26. 26.↵
    1. MacDonald IA,
    2. Kuehn MJ
    . 2013. Stress-induced outer membrane vesicle production by Pseudomonas aeruginosa. J Bacteriol195:2971–2981. doi:10.1128/JB.02267-12.
    OpenUrlAbstract/FREE Full Text
  27. 27.↵
    1. McBroom AJ,
    2. Kuehn MJ
    . 2007. Release of outer membrane vesicles by Gram-negative bacteria is a novel envelope stress response. Mol Microbiol63:545–558. doi:10.1111/j.1365-2958.2006.05522.x.
    OpenUrlCrossRefPubMedWeb of Science
  28. 28.↵
    1. Proulx F,
    2. Seidman EG,
    3. Karpman D
    . 2001. Pathogenesis of Shiga toxin-associated hemolytic uremic syndrome. Pediatr Res50:163–171. doi:10.1203/00006450-200108000-00002.
    OpenUrlCrossRefPubMedWeb of Science
  29. 29.↵
    1. Tajiri H,
    2. Nishi J,
    3. Ushijima K,
    4. Shimizu T,
    5. Ishige T,
    6. Shimizu M,
    7. Tanaka H,
    8. Brooks S
    . 2015. A role for fosfomycin treatment in children for prevention of haemolytic-uraemic syndrome accompanying Shiga toxin-producing Escherichia coli infection. Int J Antimicrob Agents46:586–589. doi:10.1016/j.ijantimicag.2015.08.006.
    OpenUrlCrossRefPubMed
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Antibiotic-Mediated Modulations of Outer Membrane Vesicles in Enterohemorrhagic Escherichia coli O104:H4 and O157:H7
Andreas Bauwens, Lisa Kunsmann, Helge Karch, Alexander Mellmann, Martina Bielaszewska
Antimicrobial Agents and Chemotherapy Aug 2017, 61 (9) e00937-17; DOI: 10.1128/AAC.00937-17

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Antibiotic-Mediated Modulations of Outer Membrane Vesicles in Enterohemorrhagic Escherichia coli O104:H4 and O157:H7
Andreas Bauwens, Lisa Kunsmann, Helge Karch, Alexander Mellmann, Martina Bielaszewska
Antimicrobial Agents and Chemotherapy Aug 2017, 61 (9) e00937-17; DOI: 10.1128/AAC.00937-17
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KEYWORDS

Anti-Bacterial Agents
Cell Membrane Structures
Escherichia coli O104
Escherichia coli O157
Shiga Toxin 2
antibiotics
enterohemorrhagic E. coli
hemolytic uremic syndrome
outer membrane vesicles
Shiga toxins

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