Startseite Human glucose-dependent insulinotropic polypeptide (GIP) is an antimicrobial adjuvant re-sensitising multidrug-resistant Gram-negative bacteria
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Human glucose-dependent insulinotropic polypeptide (GIP) is an antimicrobial adjuvant re-sensitising multidrug-resistant Gram-negative bacteria

  • Da’san M. M. Jaradat EMAIL logo , Nehaya Al-Karablieh , Basmah H. M. Zaarer , Wenyi Li , Khalil K.Y. Saleh , Anas J. Rasras , Saeid Abu-Romman , Neil M. O’Brien-Simpson EMAIL logo und John D. Wade ORCID logo EMAIL logo
Veröffentlicht/Copyright: 11. Januar 2021
Biological Chemistry
Aus der Zeitschrift Biological Chemistry Band 402 Heft 4

Abstract

Increasing antibiotic resistance in Gram-negative bacteria has mandated the development of both novel antibiotics and alternative therapeutic strategies. Evidence of interplay between several gastrointestinal peptides and the gut microbiota led us to investigate potential and broad-spectrum roles for the incretin hormone, human glucose-dependent insulinotropic polypeptide (GIP) against the Enterobacteriaceae bacteria, Escherichia coli and Erwinia amylovora. GIP had a potent disruptive action on drug efflux pumps of the multidrug resistant bacteria E. coli TG1 and E. amylovora 1189 strains. The effect was comparable to bacterial mutants lacking the inner and outer membrane efflux pump factor proteins AcrB and TolC. While GIP was devoid of direct antimicrobial activity, it has a potent membrane depolarizing effect, and at low concentrations, it significantly potentiated the activity of eight antibiotics and bile salt by reducing MICs by 4-8-fold in E. coli TG1 and 4-20-fold in E. amylovora 1189. GIP can thus be regarded as an antimicrobial adjuvant with potential for augmenting the available antibiotic arsenal.

Keywords: antibiotic adjuvant; efflux pump inhibitors; glucose-dependent insulinotropic polypeptide; mean inhibitory concentration; potentiation of antimicrobial activity; solid-phase peptide synthesis
Corresponding author: Da’san M. M. Jaradat, Faculty of Science, Department of Chemistry, Al-Balqa Applied University, P.O. Box 19117, Al-Salt, Jordan, E-mail: ; Neil M. O’Brien-Simpson, The Bio21 Institute of Molecular Science and Biotechnology, Melbourne Dental School, Centre for Oral Health Research, University of Melbourne, Melbourne, Victoria 3010, Australia, E-mail: ; and John D. Wade, School of Chemistry, University of Melbourne, Melbourne, Victoria 3010, Australia; and Howard Florey Research Laboratories, Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria 3010, Australia, E-mail:

Funding source: Australian Research Council

Award Identifier / Grant number: DP160101312

Award Identifier / Grant number: LE200100163

Funding source: National Health and Medical Research Council

Award Identifier / Grant number: APP1142472

Award Identifier / Grant number: APP1158841

Award Identifier / Grant number: APP1185426

Award Identifier / Grant number: APP1117483

Funding source: Scientific Research Support Fund of Jordan

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: The authors gratefully acknowledge the financial support by Scientific Research Support Fund of Jordan (SRSF). Eng. Rakeen Abuhanih (GMA Jordan) is thanked for the helpful discussions and careful proofreading. The authors would also like to thank Jordan Center for Pharmaceutical Research (JCPR) for their help in mass spectrometry (MS) measurements. The National Health and Medical Research Council (NHMRC) of Australia and Australian Research Council (ARC) are thanked for financial support over many years for the peptide chemistry and chemical biology studies reported in the authors’ laboratories. NMOS is the recipient of NHMRC funding (APP1142472, APP1158841, APP1185426), ARC funding (DP160101312, LE200100163), Cancer Council Victoria funding (APP1163284) and Australian Dental Research Funding in antimicrobial materials and research is supported by the Centre for Oral Health Research at The Melbourne Dental School. JDW is an NHMRC Principal Research Fellow (APP1117483). The studies undertaken in his laboratory was supported by an NHMRC Project grant (APP1158841). WL is the recipient of the 2019 Weary Dunlop Foundation grant and 2020 Early Career Researcher grant scheme of the University of Melbourne. Research at The Florey Institute of Neuroscience and Mental Health is supported by the Victorian Government Operational Infrastructure Support Program.

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2020-0351).

Received: 2020-10-23
Accepted: 2020-12-09
Published Online: 2021-01-11
Published in Print: 2021-03-26

© 2020 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Minireview
  3. Regulation of RNA stability at the 3′ end
  4. Research Articles/Short Communications
  5. Protein Structure and Function
  6. Phage-display reveals interaction of lipocalin allergen Can f 1 with a peptide resembling the antigen binding region of a human γδT-cell receptor
  7. Membranes, Lipids, Glycobiology
  8. Apolipoprotein C-II and C-III preferably transfer to both high-density lipoprotein (HDL)2 and the larger HDL3 from very low-density lipoprotein (VLDL)
  9. Molecular Medicine
  10. Dihydroartemisinin ameliorates balloon injury-induced neointimal formation through suppressing autophagy in vascular smooth muscle cells
  11. Cell Biology and Signaling
  12. HDAC8 promotes daunorubicin resistance of human acute myeloid leukemia cells via regulation of IL-6 and IL-8
  13. Hsa-miR-186-5p regulates TGFβ signaling pathway through expression suppression of SMAD6 and SMAD7 genes in colorectal cancer
  14. Lysine acetyltransferase Tip60 acetylates the APP adaptor Fe65 to increase its transcriptional activity
  15. Vorinostat exhibits anticancer effects in triple-negative breast cancer cells by preventing nitric oxide-driven histone deacetylation
  16. Human glucose-dependent insulinotropic polypeptide (GIP) is an antimicrobial adjuvant re-sensitising multidrug-resistant Gram-negative bacteria
  17. Retraction Note
  18. Retraction note to: LncRNA MEG3 inhibits HMEC-1 cells growth, migration and tube formation via sponging miR-147
https://doi.org/10.1515/hsz-2020-0351
Schlagwörter für diesen Artikel
antibiotic adjuvant; efflux pump inhibitors; glucose-dependent insulinotropic polypeptide; mean inhibitory concentration; potentiation of antimicrobial activity; solid-phase peptide synthesis

Artikel in diesem Heft

  1. Frontmatter
  2. Minireview
  3. Regulation of RNA stability at the 3′ end
  4. Research Articles/Short Communications
  5. Protein Structure and Function
  6. Phage-display reveals interaction of lipocalin allergen Can f 1 with a peptide resembling the antigen binding region of a human γδT-cell receptor
  7. Membranes, Lipids, Glycobiology
  8. Apolipoprotein C-II and C-III preferably transfer to both high-density lipoprotein (HDL)2 and the larger HDL3 from very low-density lipoprotein (VLDL)
  9. Molecular Medicine
  10. Dihydroartemisinin ameliorates balloon injury-induced neointimal formation through suppressing autophagy in vascular smooth muscle cells
  11. Cell Biology and Signaling
  12. HDAC8 promotes daunorubicin resistance of human acute myeloid leukemia cells via regulation of IL-6 and IL-8
  13. Hsa-miR-186-5p regulates TGFβ signaling pathway through expression suppression of SMAD6 and SMAD7 genes in colorectal cancer
  14. Lysine acetyltransferase Tip60 acetylates the APP adaptor Fe65 to increase its transcriptional activity
  15. Vorinostat exhibits anticancer effects in triple-negative breast cancer cells by preventing nitric oxide-driven histone deacetylation
  16. Human glucose-dependent insulinotropic polypeptide (GIP) is an antimicrobial adjuvant re-sensitising multidrug-resistant Gram-negative bacteria
  17. Retraction Note
  18. Retraction note to: LncRNA MEG3 inhibits HMEC-1 cells growth, migration and tube formation via sponging miR-147
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