Journal article

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

Da'san MM Jaradat, Nehaya Al-Karablieh, Basmah HM Zaarer, Wenyi Li, Khalil KY Saleh, Anas J Rasras, Saeid Abu-Romman, Neil M O'Brien-Simpson, John D Wade

Biological Chemistry | WALTER DE GRUYTER GMBH | Published : 2021

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 memb..

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Grants

Awarded by NHMRC


Awarded by ARC


Awarded by Cancer Council Victoria funding


Awarded by NHMRC Project grant


Funding Acknowledgements

The authors gratefully acknowledge the financial support by Scientific Research Support Fund of Jordan (SRSF). Eng. Rakeen Abuhanih (GMA Jordan) is thankedforthehelpful discussionsandcarefulproofreading. 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 ResearchFellow(APP1117483). The studiesundertakeninhis laboratory was supported by an NHMRC Project grant (APP1158841). WL is the recipient of the 2019Weary 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.