Phenazine-1-carboxylic acid promotes bacterial biofilm development via ferrous iron acquisition

Area of Science:

• Microbiology
• Infectious Diseases
• Biochemistry

Background:

• Pseudomonas aeruginosa forms biofilms, increasing resistance to antimicrobials.
• Iron availability, particularly ferric iron [Fe(III)], promotes biofilm formation.
• Therapies targeting Fe(III) uptake are explored for P. aeruginosa infections.

Purpose of the Study:

• To investigate the role of phenazine-1-carboxylic acid (PCA) in P. aeruginosa biofilm formation under iron-limiting conditions.
• To determine if PCA can alleviate Fe(III) limitation and overcome antimicrobial-induced blockage of biofilm formation.
• To elucidate the mechanism by which PCA influences iron bioavailability and biofilm development.

Main Methods:

• Assessing biofilm formation in P. aeruginosa mutants lacking siderophores in the presence of PCA.
• Evaluating the effect of PCA on conalbumin-inhibited wild-type biofilm formation.
• Investigating the requirement of the Fe(II) uptake protein FeoB for PCA-mediated rescue of biofilm formation.

Main Results:

• PCA enables P. aeruginosa biofilm formation even without siderophores (pyoverdine, pyochelin) by reducing Fe(III) to Fe(II).
• PCA rescues biofilm formation blocked by the Fe(III)-binding protein conalbumin.
• The Fe(II) uptake protein FeoB is essential for PCA to facilitate biofilm formation.
• Pyocyanin (PYO) promotes biofilm formation through an iron-independent mechanism, unlike PCA.

Conclusions:

• PCA enhances P. aeruginosa biofilm formation by increasing iron bioavailability through Fe(III) reduction to Fe(II).
• PCA's mechanism involves the Fe(II) uptake system (FeoB), suggesting a role in later-stage infections where iron redox state is critical.
• PCA represents a potential therapeutic target or adjunct for treating P. aeruginosa infections by manipulating iron availability.