Functional and Genomic Characterization of a Human-Derived Lactiplantibacillus plantarum Strain LP1 with Activity Against Carbapenem-Resistant Enterobacterales.

Carbapenem-resistant Enterobacterales (CRE) constitute an urgent global health threat, and microbiota-based strategies are increasingly being sought as alternatives to conventional antibiotics. To identify a probiotic candidate with potent anti-CRE activity, we isolated human-derived Lactiplantibacillus plantarum LP1 and performed integrated phenotypic and genomic analyses. L. plantarum LP1 displayed outstanding gastrointestinal tolerance (relative survival/proliferation rate of 113.22%) and high adhesion to Caco-2 cells (99.01%), outperforming the reference strain L. plantarum ATCC 14917, while cell-free supernatants completely inhibited CRE growth and removed up to 82.31 ± 2.24% of preformed biofilms. Hybrid whole-genome sequencing produced a complete 3.31 Mb circular chromosome assembled as a single contig, comprising 3,109 coding sequences and more than 500 genes absent from the reference strain L. plantarum ATCC 14917, including 2,977 clusters of orthologous groups (COG)-classified genes (216 related to carbohydrate transport and metabolism) and 53 carbohydrate-active enzymes, consistent with the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment of carbohydrate metabolic pathways. BAGEL4 analysis identified a class IIb plantaricin gene cluster, supporting a bacteriocin-mediated mechanism of CRE inhibition. Collectively, these findings demonstrate that L. plantarum LP1 possesses strain-specific expansion of metabolic and antimicrobial functions that underpin its strong anti-CRE activity and highlight its potential as a next-generation probiotic.