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Inhibitors targeting BamA in gram-negative bacteria
Kelly M Storek1, Dawei Sun2, Steven T Rutherford1
1Department of Infectious Diseases, Genentech Inc., South San Francisco, CA, USA.
Biochimica Et Biophysica Acta. Molecular Cell Research
|October 18, 2023
Summary
Antibiotic resistance is a growing threat, especially for gram-negative bacteria lacking new drug classes. Targeting the essential BamA protein offers a promising strategy for developing novel antibiotics.
Area of Science:
- Microbiology
- Drug Discovery
- Structural Biology
Background:
- Antibiotic resistance, particularly in gram-negative bacteria, necessitates novel therapeutic strategies due to a lack of new antibiotic classes in over 60 years.
- The outer membrane of gram-negative bacteria presents a unique target landscape, with BamA identified as a critical protein for bacterial viability.
Approach:
- This review examines emerging antibacterial agents targeting BamA, including small molecules, natural products, peptides, and antibodies.
- The focus is on BamA's role in folding and inserting outer membrane proteins, making it an accessible and essential target.
Key Points:
- BamA is an essential, conserved outer membrane protein crucial for gram-negative bacterial survival.
- Inhibitors of BamA, including small molecules and biologics, have demonstrated potential in overcoming existing resistance mechanisms.
- The outer membrane localization of BamA facilitates drug access, a significant advantage for therapeutic development.
Conclusions:
- The druggability of BamA is validated by recent studies, offering a promising avenue for developing new antibiotics against resistant gram-negative pathogens.
- Further research into BamA inhibitors is crucial to address the urgent clinical need for effective treatments against challenging bacterial infections.
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