Improved therapy

It is generally recognized that any use of antimicrobials selects for antimicrobial resistance but the relative contribution of different drugs, dosages and durations of treatment to antimicrobial resistance is poorly understood. We pursue the objective of improving therapy by understanding and reducing the contribution of each of these variables to development of antimicrobial resistance. This research line includes development of new tools for discovery of innovative antimicrobials [1], combination therapies based on reversal of antimicrobial resistance [2-3], pathogen-targeted therapies with minimal impact on the commensal microbiota [4] and alternatives to conventional antimicrobials [5]. These are the current projects in this area:

Identification of novel antibiotics by hypomorphic expression of essential genes

Objective: to enhance discovery of truly novel antimicrobial classes that interfere with untapped bacterial proteins using a screening strategy based on CRISPRi (clustered regularly interspaced short palindromic repeats interference).
PI: Luca Guardabassi
Scientist in charge: Frida Svanberg
Key collaborators: John Elmerdahl Olsen, Bimal Jana and Stefano Donadio
Funding: Marie Curie Marie Sklodowska-Curie grant CARTNET

Vaccinating against Pseudomonas otitis in dogs

Objective: to gain insight into the genetic diversity of Pseudomonas aeruginosa causing chronic otitis externa in dogs, to use this information for designing one or more autogenous vaccines, and to test the efficacy of the vaccine(s) in a clinical trial.
PI and Scientist is charge: Peter Damborg
Key collaborators: Anders Miki Bojesen, Mette Schjærff & Lene Boysen
Funding: Agria och SKKs Forskningsfond

Optimizing antimicrobial treatment length for cystitis and pyoderma in dogs

Objective: to compare the clinical efficacy of two amoxicillin treatment regimens in dogs with cystitis, and two cephalexin treatment length in dogs with superficial pyoderma
PI: Peter Damborg
Scientists in charge: Peter Damborg and Jo Fjeldsted-Holm Lundsgaard
Key collaborators: Lisbeth Rem Jessen, Tina Møller Sørensen, Mette Schjærff & Lene Boysen
Funding: Agria och SKKs Forskningsfond and the Danish Veterinary Dermatology Network (DVEN)

Key references:

  1. Adler DMT, Damborg P, Verwilghen DR. 2017. The antimicrobial activity of bupivacaine, lidocaine and mepivacaine against equine pathogens: An investigation of 40 bacterial isolates. Vet J 223: 27-31.
  2. Baker KR, Jana B, Franzyk H, Guardabassi L. 2016. A high-throughput approach to identify compounds that impair envelope integrity in Escherichia coli. Antimicrob Agents Chemother 60:5995-6002.
  3. Brochmann RP, Helmfrid A, Jana B, Magnowska Z, Guardabassi L. 2016. Antimicrobial synergy between carprofen and doxycycline against methicillin-resistant Staphylococcus pseudintermedius BMC Vet Res 12:126.
  4. Baker KR, Jana B, Hansen AM, Vissing KJ, Nielsen HM, Franzyk H, Guardabassi L. 2019. Repurposing azithromycin and rifampicin against Gram-negative pathogens by combination with peptide potentiators. Int J Antimicrob Agents [Epub ahead of print].
  5. Greco I, Plahn Emborg A, Jana B, Molchanova N, Oddo A, Damborg P, Guardabassi L, Hansen PR. 2019. Characterization, mechanism of action and optimization of activity of a novel peptide-peptoid hybrid against bacterial pathogens involved in canine skin infections. Sci Rep 9: 3679.
  6. Sadaka C, Damborg P, Watts JL. 2018. High-Throughput Screen Identifying the Thiosemicarbazone NSC319726 Compound as a Potent Antimicrobial Lead Against Resistant Strains of Escherichia coli. Biomolecules 8:4.
  7. Schoster A, Guardabassi L, Staempfli HR, Abrahams M, Jalali M, Weese JS. 2016. The longitudinal effect of a multi-strain probiotic on the intestinal bacterial microbiota of neonatal foals. Equine Vet J 48:689-696.