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Decoding the Regulatory Networks of Proteus mirabilis Under Succinic Acid Stress: A Multi-Omics Approach

ABSTRACT:

Proteus mirabilis, a key catheter-associated urinary tract infection pathogen that forms antibiotic-resistant crystalline biofilms, was shown via multi-omics analyses to be multimodally inhibited by succinic acid. At 15 mM, succinic acid reduced the bacterium’s growth by 70% and biofilm formation by 50%. Metabolomics revealed dysregulation in tryptophan/arginine metabolism, nucleotide biosynthesis, and the tricarboxylic acid cycle; transcriptomics showed downregulated ribosomal genes, oxidative phosphorylation, and efflux pumps plus upregulated arginine transport; and proteomics demonstrated suppressed T6SS virulence factors and iron acquisition proteins. Mechanistically, succinic acid is proposed to reduce K6 acetylation of the histone-like nucleoid structuring protein, enhancing its oligomerization to repress T6SS genes and inhibit biofilm formation. By targeting metabolism, virulence, and stress adaptation, succinic acid circumvents single-target resistance, offering a strategy to combat multidrug-resistant P. mirabilis via biofilm disruption and pathogenicity suppression.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS12952 | MetaboLights | 2025-09-08

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS12952_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS12952_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS12952_LC-MS_negative_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular
	m_MTBLS12952_LC-MS_positive_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular

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Decoding the Regulatory Networks of Proteus mirabilis Under Succinic Acid Stress: A Multi-Omics Approach

Project description:Proteus mirabilis, a key catheter-associated urinary tract infection pathogen that forms antibiotic-resistant crystalline biofilms, was shown via multi-omics analyses to be multimodally inhibited by succinic acid. At 15 mM, succinic acid reduced the bacterium’s growth by 70% and biofilm formation by 50%. Metabolomics revealed dysregulation in tryptophan/arginine metabolism, nucleotide biosynthesis, and the tricarboxylic acid cycle; transcriptomics showed downregulated ribosomal genes, oxidative phosphorylation, and efflux pumps plus upregulated arginine transport; and proteomics demonstrated suppressed T6SS virulence factors and iron acquisition proteins. Mechanistically, succinic acid is proposed to reduce K6 acetylation of the histone-like nucleoid structuring protein, enhancing its oligomerization to repress T6SS genes and inhibit biofilm formation. By targeting metabolism, virulence, and stress adaptation, succinic acid circumvents single-target resistance, offering a strategy to combat multidrug-resistant P. mirabilis via biofilm disruption and pathogenicity suppression.The uploaded data comprise two omics datasets:Acetyl-proteomics: Folders prefixed with XB10893DPAc (treatment: H1–H3; control: T1–T3)；Proteomics: Folders prefixed with XB10893DA (treatment: H1–H3; control: T1–T3).

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Project description:Enterococcus faecalis is a commensal bacterium in the gastrointestinal tract (GIT) of humans and other organisms. Outside of the GIT, E. faecalis can cause infections in root canals, wounds, surgical sites, the urinary tract, and on heart valves. Many of these infections can be polymicrobial, and a variety of toxins and nutritional signals influence interactions between E. faecalis and other microbes. Like other bacteria, E. faecalis metabolizes arginine through the arginine deiminase (ADI) pathway, which converts arginine to ornithine and releases ATP, ammonia, and CO2. E. faecalis arginine metabolism also affects virulence of other pathogens, such as Clostridioides difficile and Escherichia coli, during co-culture. E. faecalis may encounter elevated levels of arginine in the GIT or the oral cavity, where arginine is used as an additive in dental therapeutics to disrupt plaque formation and biofilm growth by oral streptococci. However, little is known about how E. faecalis responds to growth in arginine. To address this gap, we used RNAseq and additional in vitro assays to measure changes in growth, gene expression, and biofilm formation in arginine relative to control conditions. Here, we demonstrate that arginine decreases E. faecalis biofilm production and causes widespread differential expression of genes related to metabolism, nutrient transport, quorum sensing, and polysaccharide synthesis. Growth in arginine also increases aggregation of E. faecalis cultures and promotes decreased susceptibility to the antibiotics ampicillin and ceftriaxone. Together, this shows that E. faecalis undergoes global transcriptional changes during growth in arginine and provides a platform for better understanding of how the presence of arginine in the niches colonized by E. faecalis affects the physiology of this organism in addition to the virulence of surrounding microbes.

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