Nitric Oxide restricts iron availability and induces quorum sensing in Streptococcus pyogenes

Area of Science:

• Microbiology
• Biochemistry
• Immunology

Background:

• Nitric oxide (NO) is a crucial signaling molecule in the innate immune system with antimicrobial functions.
• NO exerts cytotoxicity by metal binding, enzyme inhibition, and inducing nitrosative/oxidative stress.
• The chelatable iron pool (CIP) is a key target for NO, forming dinitrosyliron complexes (DNIC).

Purpose of the Study:

• To investigate whether NO-dependent iron restriction via DNIC formation triggers quorum sensing (QS) and iron-starvation phenotypes in Streptococcus pyogenes.
• To determine if DNIC formation directly impacts iron bioavailability and bacterial responses.

Main Methods:

• Exposure of Streptococcus pyogenes to physiologically relevant nitric oxide concentrations.
• Quantification of dinitrosyliron complexes (DNIC) formation and its effect on the chelatable iron pool (CIP).
• Analysis of QS activation and iron-regulated gene expression.

Main Results:

• DNIC formation was observed in S. pyogenes upon exposure to NO.
• DNIC formation significantly reduced the available CIP in bacteria.
• Reduced CIP correlated with activated QS and iron-regulated gene expression, affecting bacterial growth.

Conclusions:

• NO-mediated iron restriction through DNIC formation is a functional mechanism in bacteria.
• This mechanism regulates QS, gene expression, and bacterial cell growth.
• These findings provide novel insights into NO's role in host-pathogen interactions and bacterial defense.