Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2019

Repurposing the metal chelator diethyldithiocarbamate to inhibit bacterial growth of staphylococci (#172)

Laurine Kaul 1 , Andrew Zannettino 2 , Regine Suess 3 , Katharina Richter 1
  1. Richter Lab, Surgery Department, University of Adelaide, Adelaide, SA, Australia
  2. Faculty of Health and Medical Sciences, University of Adelaide, Precision Medicine Theme, South Australian Health & Medical Research Institute, Adelaide, SA, Australia
  3. Institute of Pharmaceutical Sciences, University of Freiburg, Freiburg, Germany

Background: Staphylococcus aureus and Staphylococcus epidermidis are major causes of infectious disease, including infections associated with hernia mesh and surgical sites. Current medical care fails to effectively control these infections, particularly when bacteria establish antibiotic-resistance. In addition, the formation of biofilms (i.e. bacterial clusters embedded in a protective matrix) on hernia mesh and surgical sites frequently leads to clinical complications and increased healthcare costs. The lack of effective treatment strategies to combat antibiotic-resistant bacteria and biofilms is a major unmet need.

Objective: Investigating the antibacterial activity of an innovative treatment comprising diethyldithiocarbamate (DDC) combined with copper(II) (Cu) against staphylococci.

Methods: The minimal inhibitory concentration (MIC) of DDC and Cu was determined in 2 methicillin-resistant S. aureus (MRSA 1 and MRSA 2) and 2 S. epidermidis (SE 1 and SE 2) strains. To assess the potential synergy between the two compounds, checkerboard assays were performed with planktonic and biofilm bacteria. The fractional inhibitory concentration index was calculated and used to define synergism, near synergism or additive effects of DDC and Cu.

Results: The MIC of DDC was 64 for MRSA 1 and 2, and 32 µg/ml for SE 1 and 2. The MIC of Cu was >256 µg/ml in all strains tested. Synergistic effects of DDC and Cu (DDC-Cu) were observed in the 2 planktonic MRSA strains. However, DDC-Cu reached near synergism in MRSA 1 biofilms and additive effects in MRSA 2 biofilms. In all S. epidermidis strains DDC-Cu showed additive effects in both planktonic cells and biofilms.

Conclusion: Synergistic and additive effects against MRSA and S. epidermidis make DDC-Cu a potential new treatment strategy against staphylococci. Future research will expand on current antibacterial and antibiofilm studies, and will focus on determining the mode of action of DDC-Cu. In addition, studies will focus on the development of drug-delivery approaches for applications in hernia mesh infections and surgical site infections.