Cationic Peptides Facilitate Iron-induced Mutagenesis in Bacteria

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Pseudomonas aeruginosa is a key pathogen in chronic respiratory infections, particularly in cystic fibrosis patients.
• Adaptive mutations are crucial for P. aeruginosa's antimicrobial resistance and persistence.
• The environmental factors driving mutagenesis in P. aeruginosa remain unclear.

Purpose of the Study:

• To investigate the potential mutagenic effects of cationic antimicrobial peptides (LL-37) and free iron on P. aeruginosa.
• To determine if LL-37 and iron act synergistically to induce mutations.
• To elucidate the mechanism of LL-37-induced mutagenesis.

Main Methods:

• Mutation rate estimation in P. aeruginosa exposed to LL-37, iron, or both.
• Assessment of mutant frequencies and mutational spectra.
• Evaluation of the effect of an iron chelator on mutagenesis.
• Analysis of mutational spectrum for Fenton reaction fingerprints.

Main Results:

• Mutation rate and mutant frequency increased significantly only when LL-37 and free iron were present together.
• Colistin, another antimicrobial peptide, exhibited similar mutagenic effects in combination with iron.
• An iron chelator completely abolished the mutagenic effect, indicating iron's essential role.
• The mutational spectrum showed a characteristic Fenton reaction fingerprint (C to T transitions).

Conclusions:

• LL-37 and free iron act synergistically to induce mutagenesis in P. aeruginosa.
• LL-37 likely facilitates iron entry into cells, leading to DNA damage via Fenton reactions.
• Elevated free iron in cystic fibrosis lung infections may contribute to increased mutagenesis and disease severity.