Human glucose-dependent insulinotropic polypeptide (GIP) is an antimicrobial adjuvant re-sensitising multidrug-resistant Gram-negative bacteria-Reference-Cited by-同舟云学术

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

Published:2021-01-11 Issue:4 Volume:402 Page:513-524
ISSN:1437-4315
Container-title:Biological Chemistry
language:en
Short-container-title:

Author:

Jaradat Da’san M. M.¹,Al-Karablieh Nehaya²³,Zaarer Basmah H. M.¹,Li Wenyi⁴,Saleh Khalil K.Y.¹,Rasras Anas J.¹,Abu-Romman Saeid⁵,O’Brien-Simpson Neil M.⁴,Wade John D.⁶⁷^ORCID

Affiliation:

1. Faculty of Science, Department of Chemistry , Al-Balqa Applied University , P.O. Box 19117 , Al-Salt , Jordan

2. Faculty of Agriculture, Department of Plant Protection , The University of Jordan , Amman , Jordan

3. Hamdi Mango Center for Scientific Research , The University of Jordan , Amman , Jordan

4. The Bio21 Institute of Molecular Science and Biotechnology, Melbourne Dental School , Centre for Oral Health Research, University of Melbourne , Melbourne , Victoria 3010 , Australia

5. Faculty of Agricultural Technology, Department of Biotechnology , Al-Balqa Applied University , P.O. Box 19117 , Al-Salt , Jordan

6. School of Chemistry , University of Melbourne , Melbourne , Victoria 3010 , Australia

7. Howard Florey Research Laboratories, Florey Institute for Neuroscience and Mental Health , University of Melbourne , Melbourne , Victoria 3010 , Australia

Abstract

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.

Funder

Australian Research Council

National Health and Medical Research Council

Scientific Research Support Fund of Jordan

Publisher

Walter de Gruyter GmbH

Subject

Clinical Biochemistry,Molecular Biology,Biochemistry

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