Potentiation and repurposing of macrolide antimicrobials against Gram-negative pathogens for clinical applications in human and veterinary medicine

Liam Good (primary)
Royal Veterinary College, PPS
Royal Veterinary College
Wenhui Song (secondary)
Department of Surgical Biotechnology Div of Surgery & Interventional Sci Faculty of Medical Sciences
UCL

Abstract

The development of improved antibacterial strategies is an important global challenge. This project aims to potentiate the activity of non-critical macrolide antibiotics to the degree that they can be used to replace the use of critical antibiotics in clinical use in human and veterinary medicine, e.g., colistin. This aim will be achieved by complexing and conjugating macrolide antibiotics with peptide mimics (peptidomimetics) and antimicrobial polymers, building on strong in vitro evidence in our laboratories. The antibacterial, immunomodulatory and microbiome effects will be tested in vitro and in vivo, and by using cell systems and porcine and/or avian models.


References

Baker KR1, Jana B2, Hansen AM3, Vissing KJ4, Nielsen HM4, Franzyk H5, Guardabassi L2. Repurposing azithromycin and rifampicin against Gram-negative pathogens by combination with peptide potentiators. Int J Antimicrob Agents. 2018 Nov 14. pii: S0924-8579(18)30317-0. doi: 10.1016/j.ijantimicag.2018.10.025.

Kamaruzzaman, Nor Fadhilah; Firdessa, Rebuma; Good, Liam. (2016) Bactericidal effects of polyhexamethylene biguanide against intracellular Staphylococcus aureus EMRSA-15 and USA 300.
Journal of Antimicrobial Chemotherapy. 71(5):1252-1259, May 2016.

Chindera, K., Mahato, M., Sharma, AK., Horsley, H., Kloc-Muniak, K., McFarlane, A., Stach, J., Bentin, T., Good, L. (2016). The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes. Nature Scientific Reports, 6, 23121. Retrieved from http://dx.doi.org/10.1038/srep23121

Baker KR1, Jana B2, Franzyk H3, Guardabassi L1. A High-Throughput Approach To Identify Compounds That Impair Envelope Integrity in Escherichia coli. Antimicrob Agents Chemother. 2016 Sep 23;60(10):5995-6002. doi: 10.1128/AAC.00537-16. Print 2016 Oct.

Anna Worsley 1,2,* , Kristin Vassileva 1,2, Janice Tsui 2 , Wenhui Song 2 and Liam Good Polyhexamethylene Biguanide:Polyurethane BlendNanofibrous Membranes forWound Infection Control. Polymers 2019, 11, 915; doi:10.3390/


BBSRC Area
Plants, microbes, food and sustainability
Area of Biology
Chemical BiologyMicrobiology
Techniques & Approaches
BiochemistryChemistryEngineeringImage ProcessingMathematics / StatisticsMicroscopy / ElectrophysiologySimulation / Modelling