The interplay of specialized metabolites, antibiotic resistance, and virulence in Enterococcus faecium: in silico analysis of bacterial genomes

BACKGROUND: Enterococcus faecium is a prominent Gram-positive nosocomial pathogen associated with high morbidity and mortality worldwide. Identification of its antimicrobial resistance (AMR) genes, virulence factors, and biosynthetic gene clusters (BGCs) encoding specialized metabolites is essential as a preliminary step toward developing novel therapeutic interventions. This study aimed to explore the relationship between BGCs, AMR and virulence attributes in 81 E. faecium genomes-retrieved from the Genome Taxonomy Database (GTDB)-using different computational tools, including antiSMASH, GECCO and Clinker. We assessed the prevalence, co-occurrence and associations between all identified traits. RESULTS: Nearly 50% of the 334 total detected BGCs were identified as RiPP-like clusters, with the majority predicted to encode bacteriocin-related products. Certain clusters of cyclic lactone autoinducers (CAL-BGCs) showed genomic rearrangements or unique sequences, suggesting diversity in quorum-sensing potential or signaling systems. Several primary metabolic gene clusters (MGCs) were also identified, including the arginine deiminase system, PFOR-II, and gallic acid metabolism, suggesting roles in energy adaptation and gut colonization. Both BGCs and MGCs show relatively high conserved profiles. The virulence genes: acm, scm, fss3, sgrA and ecbA were present at variable levels, implying differences in host-cell binding abilities and biofilm formation. AMR profiling showed an extremely high resistance profile in most genomes, where 43 AMR genes were detected, such as vancomycin resistance clusters (vanA-type), aac(6')-Ii, and msrC. Concurrent resistance for 5 or more classes of antibiotics was detected in approximately 70% of the studied genomes. Epidemiological integration showed strong sequence type (ST) structuring across geography and clinical source, with lineage-dependent variation in AMR burden but relatively conserved virulence and BGC profiles. CONCLUSION: This study highlights the metabolic and genomic plasticity of E. faecium, especially its dynamic AMR profile, which reflects its high pathogenicity and environmental resilience. Our results underscore the importance of the concurrent exploration of specialized metabolites, resistance and virulence traits to gain insights into the pathogen's survival mechanisms and identify potential targets for novel therapeutics. Nevertheless, further experimental validation of these computational results will deepen our understanding of this pathogen and will aid in the battle against AMR bacteria.