Overcoming intrinsic and acquired resistance mechanisms associated with the cell wall of gram-negative bacteria
journal contribution
posted on 2025-01-22, 00:45authored byRachael Impey, Daniel HawkinsDaniel Hawkins, JM Sutton, Tatiana Soares-da-Costa
The global increase in multi-drug-resistant bacteria is severely impacting our ability to effectively treat common infections. For Gram-negative bacteria, their intrinsic and acquired resistance mechanisms are heightened by their unique cell wall structure. The cell wall, while being a target of some antibiotics, represents a barrier due to the inability of most antibacterial compounds to traverse and reach their intended target. This means that its composition and resulting mechanisms of resistance must be considered when developing new therapies. Here, we discuss potential antibiotic targets within the most well-characterised resistance mechanisms associated with the cell wall in Gram-negative bacteria, including the outer membrane structure, porins and efflux pumps. We also provide a timely update on the current progress of inhibitor development in these areas. Such compounds could represent new avenues for drug discovery as well as adjuvant therapy to help us overcome antibiotic resistance.
Funding
This research was funded by the National Health and Medical Research Council of Australia, grant number APP1091976, and the Australian Research Council, grant number DE190100806.