Virtual Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2022

Efficacy of a metal chelator as antibacterial agent against staphylococci biofilms (82315)

Laurine Kaul 1 2 , Regine Süss 2 , Andrew Zannettino 1 , Katharina Richter 1
  1. University of Adelaide, Adelaide, SA, Australia
  2. University of Freiburg, Freiburg, Germany

Background: Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis) are associated with many clinical infections, such as surgical site infections. These major infectious diseases frequently lead to clinical complications and increased healthcare costs, as standard treatments fail due to the rise of antibiotic resistance and the formation of biofilms. Therefore, new antibacterial treatments are urgently needed.

Aim: To investigate a newly patented combination therapy comprising the metal chelator diethyldithiocarbamate (DDC) and copper ions (Cu2+) against staphylococci biofilms.

Methods: DDC and Cu2+ were tested in vitro for their antibacterial activity against methicillin-resistant S. aureus (MRSA) and S. epidermidis using the AlarmarBlue viability assay. Prevention of bacterial attachment was assessed with the xCELLigence system. In vivo toxicity and efficacy of the DDC-Cu2+ combination was investigated in infected Galleria mellonella larvae over 4 days. Statistical analysis: log-rank test with Holm-Bonferroni adjustment of Kaplan-Meier survival curves.

Results: While DDC and Cu2+ alone failed to show substantial antibacterial activity, the DDC-Cu2+ combination demonstrated concentration-dependent antibacterial properties, with 99% MRSA and 87% S. epidermidis biofilm killing. When left untreated, staphylococci attached to surfaces over 48 h (cell index of MRSA: 0.50; S. epidermidis: 0.46), but attachment was prevented when treated with DDC-Cu2+ (cell index of MRSA: 0.04; S. epidermidis: 0.03). DDC-Cu2+ showed no toxicity in Galleria mellonella larvae and significantly increased the survival of MRSA infected larvae over 4 days (87% survival of infected, treated larvae vs. 47% survival of infected, untreated larvae, p<0.001).

Conclusion: DDC-Cu2+ effectively inhibited the attachment of staphylococci biofilms in vitro and showed non-toxicity and antimicrobial activity in vivo. Delivered in a thermosensitive gel, DDC-Cu2+ has capacity to progress to mammalian animal studies for the treatment of surgical site infections.