Decoding the regulatory networks of Proteus mirabilis under succinic acid stress: a multi-omics approach

Area of Science:

• Microbiology
• Biochemistry
• Molecular Biology

Background:

• Proteus mirabilis is a primary cause of catheter-associated urinary tract infections (CAUTIs).
• P. mirabilis forms antibiotic-resistant crystalline biofilms, complicating treatment.
• Developing new strategies to combat resistant P. mirabilis is crucial.

Purpose of the Study:

• To investigate the multimodal inhibitory effects of succinic acid on P. mirabilis.
• To elucidate the molecular mechanisms underlying succinic acid's action against P. mirabilis growth and biofilm formation.

Main Methods:

• Multi-omics analyses including metabolomics, transcriptomics, and proteomics were employed.
• Bacterial growth and biofilm formation assays were conducted.
• Acetylation assays were performed to assess histone-like protein modification.

Main Results:

• Succinic acid (15 mM) significantly reduced P. mirabilis growth (≥70%) and biofilm formation (≥50%).
• Metabolomics revealed dysregulation in tryptophan, arginine metabolism, nucleotide biosynthesis, and TCA cycle.
• Transcriptomics and proteomics identified altered ribosomal genes, oxidative phosphorylation, efflux pumps, arginine transport, T6SS virulence factors, and iron acquisition proteins.

Conclusions:

• Succinic acid inhibits P. mirabilis by targeting metabolism, virulence, and stress adaptation pathways.
• Succinic acid reduces K6 acetylation of histone-like proteins, repressing T6SS genes and inhibiting biofilm formation.
• Succinic acid presents a promising strategy to combat multidrug-resistant P. mirabilis by disrupting biofilms and suppressing pathogenicity.