OpenLB
Open Library of Bioscience
Advanced Search
Molecules (Basel, Switzerland)
May 23, 2023;28 (11):

Scope and Limitations of Exploiting the Ability of the Chemosensitizer NV716 to Enhance the Activity of Tetracycline Derivatives against .

Margot Draveny, Clémence Rose, Alexis Pinet, Laurent Ferrié, Bruno Figadère, Jean-Michel Brunel, Muriel Masi
Author Information
  1. Margot Draveny: MCT, INSERM U1261, UMR_MD1, Aix-Marseille Univ. & IRBA SSA, 27 Boulevard Jean Moulin, 13005 Marseille, France.
  2. Clémence Rose: BioCIS, Bâtiment H. Moissan, Université Paris-Saclay, CNRS, 91400 Orsay, France.
  3. Alexis Pinet: BioCIS, Bâtiment H. Moissan, Université Paris-Saclay, CNRS, 91400 Orsay, France.
  4. Laurent Ferrié: BioCIS, Bâtiment H. Moissan, Université Paris-Saclay, CNRS, 91400 Orsay, France. ORCID
  5. Bruno Figadère: BioCIS, Bâtiment H. Moissan, Université Paris-Saclay, CNRS, 91400 Orsay, France. ORCID
  6. Jean-Michel Brunel: MCT, INSERM U1261, UMR_MD1, Aix-Marseille Univ. & IRBA SSA, 27 Boulevard Jean Moulin, 13005 Marseille, France. ORCID
  7. Muriel Masi: MCT, INSERM U1261, UMR_MD1, Aix-Marseille Univ. & IRBA SSA, 27 Boulevard Jean Moulin, 13005 Marseille, France. ORCID
PMID: 37298737 DOI: 10.3390/molecules28114262

Abstract

The spread of antibiotic resistance is an urgent threat to global health that requires new therapeutic approaches. Treatments for pathogenic Gram-negative bacteria are particularly challenging to identify due to the robust OM permeability barrier in these organisms. One strategy is to use antibiotic adjuvants, a class of drugs that have no significant antibacterial activity on their own but can act synergistically with certain antibiotics. Previous studies described the discovery and development of polyaminoisoprenyl molecules as antibiotic adjuvants with an OM effect. In particular, the compound NV716 has been shown to sensitize to Tetracycline antibiotics such as doxycycline. Here, we sought to explore the disruption of OM to sensitize to otherwise inactive antimicrobials using a series of Tetracycline derivatives in the presence of NV716. We found that OM disruption expands the hydrophobicity threshold consistent with antibacterial activity to include hydrophobic molecules, thereby altering permeation rules in Gram-negative bacteria.

Keywords

Gram-negative bacteria NV716 antibiotic adjuvant antibiotic resistance outer membrane

References

  1. Molecules. 2023 Feb 13;28(4): [PMID: 36838752]
  2. Nat Rev Microbiol. 2020 Mar;18(3):164-176 [PMID: 31792365]
  3. Antibiotics (Basel). 2012 Jun 12;1(1):1-13 [PMID: 27029415]
  4. mBio. 2017 Oct 31;8(5): [PMID: 29089426]
  5. Antimicrob Agents Chemother. 1984 Jul;26(1):48-52 [PMID: 6433788]
  6. mBio. 2020 Sep 22;11(5): [PMID: 32963002]
  7. Cold Spring Harb Perspect Med. 2016 Oct 3;6(10): [PMID: 27503996]
  8. Microbiol Rev. 1985 Mar;49(1):1-32 [PMID: 2580220]
  9. Eur J Med Chem. 2022 Aug 5;238:114496 [PMID: 35691172]
  10. Ann N Y Acad Sci. 2020 Jan;1459(1):69-85 [PMID: 31762048]
  11. Clin Microbiol Rev. 2015 Apr;28(2):337-418 [PMID: 25788514]
  12. J Antibiot (Tokyo). 2017 Apr;70(4):386-394 [PMID: 28074057]
  13. Microbiol Rev. 1992 Sep;56(3):395-411 [PMID: 1406489]
  14. Commun Biol. 2022 Aug 25;5(1):871 [PMID: 36008485]
  15. Ann N Y Acad Sci. 2019 Jan;1435(1):18-38 [PMID: 29446459]
  16. Front Microbiol. 2019 Aug 13;10:1771 [PMID: 31456758]
  17. Int J Mol Sci. 2021 Mar 10;22(6): [PMID: 33802163]
  18. Nat Microbiol. 2017 Mar 06;2:17028 [PMID: 28263303]
  19. Clin Neuropharmacol. 2003 Jan-Feb;26(1):18-23 [PMID: 12567160]
  20. ACS Cent Sci. 2022 Aug 24;8(8):1145-1158 [PMID: 36032774]
  21. Nat Microbiol. 2020 Jan;5(1):67-75 [PMID: 31740764]
  22. Nature. 2017 May 18;545(7654):299-304 [PMID: 28489819]
  23. Microbiol Mol Biol Rev. 2003 Dec;67(4):593-656 [PMID: 14665678]
  24. Molecules. 2019 Jan 11;24(2): [PMID: 30641878]
  25. Cells. 2022 Sep 04;11(17): [PMID: 36078167]
  26. Antioxidants (Basel). 2023 Feb 24;12(3): [PMID: 36978822]
  27. Nature. 2016 Jan 21;529(7586):336-43 [PMID: 26791724]
  28. PLoS One. 2016 May 06;11(5):e0154490 [PMID: 27152508]
  29. Cells. 2021 Aug 22;10(8): [PMID: 34440932]
  30. Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):E2629-34 [PMID: 23798411]
  31. Antimicrob Agents Chemother. 2016 Nov 21;60(12):7372-7381 [PMID: 27697764]
  32. mBio. 2020 Mar 10;11(2): [PMID: 32156814]
  33. Antimicrob Agents Chemother. 2021 Feb 17;65(3): [PMID: 33318000]
  34. Ann N Y Acad Sci. 2020 Jan;1459(1):5-18 [PMID: 31165502]
  35. J Med Chem. 2008 May 22;51(10):2871-8 [PMID: 18260614]
  36. Nat Rev Microbiol. 2020 May;18(5):286-298 [PMID: 32152509]
  37. Lancet. 1997 Feb 8;349(9049):418-22 [PMID: 9033483]
  38. Antimicrob Agents Chemother. 2003 Dec;47(12):3675-81 [PMID: 14638464]
  39. Nat Rev Microbiol. 2020 May;18(5):275-285 [PMID: 31745331]
  40. Future Med Chem. 2016 Jun;8(9):963-73 [PMID: 27227839]
  41. Cell. 2000 Dec 22;103(7):1143-54 [PMID: 11163189]
  42. J Med Chem. 2020 Sep 24;63(18):10496-10508 [PMID: 32840108]
  43. PLoS Biol. 2012 Jan;10(1):e1001242 [PMID: 22272184]
  44. J Med Chem. 2014 Dec 11;57(23):10144-61 [PMID: 25402200]
  45. Antimicrob Agents Chemother. 2017 Jul 25;61(8): [PMID: 28533232]

Grants

  1. GAO2018/France Parkinson

MeSH Term

Pseudomonas aeruginosa
Anti-Bacterial Agents
Tetracycline
Drug Resistance, Microbial
Microbial Sensitivity Tests
Gram-Negative Bacteria

Chemicals

Anti-Bacterial Agents
Tetracycline
Journal Article
Article has an altmetric score of 1

Word Cloud

Created with Highcharts 10.0.0antibioticOMNV716Gram-negativebacteriaresistanceadjuvantsantibacterialactivityantibioticsmoleculessensitizetetracyclinedisruptionspreadurgentthreatglobalhealthrequiresnewtherapeuticapproachesTreatmentspathogenicparticularlychallengingidentifyduerobustpermeabilitybarrierorganismsOnestrategyuseclassdrugssignificantcanactsynergisticallycertainPreviousstudiesdescribeddiscoverydevelopmentpolyaminoisoprenyleffectparticularcompoundshowndoxycyclinesoughtexploreotherwiseinactiveantimicrobialsusingseriesderivativespresencefoundexpandshydrophobicitythresholdconsistentincludehydrophobictherebyalteringpermeationrulesScopeLimitationsExploitingAbilityChemosensitizerEnhanceActivityTetracyclineDerivativesadjuvantoutermembrane

Similar Articles

Cited By

No available data.