Oral Presentation BacPath 2024

Utilizing gallium liquid metal to control the pathogenicity of Acinetobacter baumannii (#10)

Mohammadreza Mahzounieh 1 , Vi Khanh Truong 2 , Tien Thanh Nguyen 2 , Richard Bright 2 , Melissa H Brown 1 3
  1. College of Science and Engineering, Flinders University, Bedford Park, SA, Australia
  2. College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia
  3. ARC Training Centre for Biofilms and Innovation, Bedford Park, SA, Australia

Acinetobacter baumanni has emerged as a significant cause of nosocomial infections due to its remarkable ability to develop resistance to multiple antibiotics, posing a substantial threat in healthcare settings. As conventional antibiotics become increasingly ineffective, the search for novel antimicrobial agents has intensified. Among the promising candidates, gallium liquid metal (GaLM) has garnered significant attention in multidisciplinary research due to its potent inhibitory effects against bacteria, although the precise mechanism of action remains unclear (2). Due to their physical and chemical similarity to ferric ions, gallium ions can bind to bacterial siderophores and be actively taken up by the bacteria. However, unlike iron, gallium cannot be reduced by bacterial enzymes, leading to iron deprivation, disruption of iron homeostasis, and the generation of reactive oxygen species. In this study, GaLM was mixed with three polymers: Pluronic F-127 (PF-127), polyetherimide (PEI), and deferoxamine B (DFO-B) and applied to multiple strains of A. baumannii. Interestingly, our findings show that the stability, bioavailability, and antimicrobial efficacy of GaLM are enhanced by the addition of PF-127 and DFO-B, but not PEI. Resistance to GaLM increases when iron concentrations exceed 1.5 mg/ml, highlighting the competitive interaction between iron and gallium ions. This study demonstrates that GaLM can inhibit the growth and modify pathogenic determinants of A. baumannii by disrupting iron homeostasis and impeding the development of biofilm formation, capsules, pellicles, and twitching motility, while exhibiting no toxicity towards human THP-1 cells. Results suggest that the antimicrobial mechanism of GaLM might be linked to the release of gallium ions, but more studies are required to further understand the mechanisms of GaLM (1). In conclusion, GaLM offers a novel and promising approach to combating multidrug-resistant A. baumannii, providing a potential solution to the growing problem of antibiotic resistance.

  1. LIMANTORO, C., et al. 2023. Synthesis of Antimicrobial Gallium Nanoparticles Using the Hot Injection Method. ACS Materials Au, 3, 310-320. https://doi.org/10.1021/acsmaterialsau.2c00078
  2. TRUONG, V. K., et al. 2023. Gallium Liquid Metal: Nanotoolbox for Antimicrobial Applications. ACS Nano, 17, 14406-14423. https://www.ncbi.nlm.nih.gov/pubmed/37506260