Transcriptomic insights into the antimicrobial effect of Pediococcus pentosaceus on multidrug-resistant Pseudomonas aeruginosa

Antimicrobial resistance in Pseudomonas aeruginosa is a critical global health challenge. In this study, we profiled the transcriptomic response of multidrug resistant P. aeruginosa PA01 to the cell-free supernatant of Pediococcus pentosaceus ENM104. Differential expression analysis using edgeR (|log₂FC| ≥ 2, FDR ≤ 0.05) identified a high-confidence set of 952 core differentially expressed genes (492 upregulated, 460 downregulated). Functional enrichment (GO/KEGG) and STRING v12.0 mapping revealed a shift prioritizing protein synthesis and envelope defense with induction of ribosomal proteins, aminoacyl tRNA synthetases and components of oxidative phosphorylation. Additionally, antimicrobial peptide (AMP) resistance appears reinforced through PhoQ/Arn mediated L-Ara4N lipid-A remodeling and increased expression of the MexAB-OprM efflux system. Transcriptomic signatures also suggest metabolic rewiring consistent with acid stress adaptation along with broad attenuation of proteostasis mechanisms. The upregulation of pnp (encoding PNPase) suggests increased RNA turnover and quality control. These changes may support homeostatic adjustment and tolerance to acid and AMP stress. However, this study lacks biological replicates, and dispersion was assumed in edgeR. Future work should identify the active CFS constituents and validate key nodes by qRT-PCR assays.