Pan-genome analysis reveals the triangle mechanisms of antibiotic resistance, pathogenicity, and biofilm formation in Enterococcus faecalis

Antibiotic resistance in Pseudomonas aeruginosa: mechanisms, diagnostic challenges, and omics-based diagnostic solutions

Pseudomonas aeruginosa is considered a multidrug resistant opportunistic pathogen associated with severe infections in immunocompromised patients. Owing to its diverse intrinsic and adaptive resistance strategies, as well as its capacity for horizontal gene transfer, P. aeruginosa represents a major contributor to the global antimicrobial resistance burden. Its remarkable ability to evade antibiotics arises from a wide range of mechanisms, including efflux pumps overexpression, porin modification, enzymatic inactivation and target site modifications, alongside phenotypic adaptations such as biofilm and persister cell formation. These complex resistance strategies of the organism have fueled the global emergence of multidrug resistant, extensively drug resistant and even pan drug resistant strains. These strains significantly complicate the treatment strategies. Conventional culture-based diagnostics are still considered the gold standard, yet their delays and limitations in detecting heteroresistance and biofilm-associated tolerance hinder timely therapeutic intervention. Recent advances in omics-based approaches, including genomics, epigenomics, transcriptomics, proteomics, lipidomics, metabolomics, and phenomics, provide powerful alternatives for rapid and precise identification of resistant P. aeruginosa. In parallel, innovative diagnostic platforms such as microfluidic lab on chip systems and machine learning driven artificial intelligence further enhance diagnostic resolution. Therefore, multi omics integration, coupled with advanced platforms would be a revolutionary strategy to deliver comprehensive and rapid resistance profiling in precision diagnostics. To convert this potential into practice, proper planning, standardized protocols, clinical validation and cost-effective implementation are urgently needed. Together, these advancements pave the way toward outpacing resistance in P. aeruginosa and reducing the global burden of antimicrobial resistance.

Antimicrobial resistance mechanisms, treatment challenges, and emerging strategies in Stenotrophomonas maltophilia infections

Stenotrophomonas maltophilia is a Gram-negative opportunistic pathogen widely distributed in natural and clinical environments, and has increasingly been recognized as a significant cause of nosocomial infections. Owing to its complex intrinsic resistance mechanisms and the continuous evolution of acquired resistance, the clinical management of S. maltophilia infections remains highly challenging. Resistance in S. maltophilia is mediated by multiple mechanisms, including chromosomally encoded L1/L2 β-lactamases, multidrug efflux pump systems, reduced outer membrane permeability, and biofilm formation, as well as the acquisition of resistance determinants via mobile genetic elements. In addition, virulence-associated traits, including quorum sensing systems, and extracellular enzyme production, contribute to host adaptation and persistent infection. Trimethoprim–sulfamethoxazole (TMP–SMX) remains the first-line therapy. However, increasing resistance has been reported in certain regions. Alternative and combination therapies, including minocycline and fluoroquinolones, are increasingly utilized. Meanwhile, emerging strategies such as efflux pump inhibitors, anti-virulence approaches, and bacteriophage therapy have attracted growing attention. This review provides a comprehensive overview of the resistance mechanisms, virulence-associated phenotypes, and current therapeutic advances of S. maltophilia, with particular emphasis on resistance evolution and novel treatment strategies. These insights may advance our understanding of host–pathogen interactions and support the development of targeted therapeutic approaches for improved clinical management.

Clade-specific evolution and genome plasticity underlying antimicrobial resistance in Enterococcus faecium

Genetic architecture and functional dynamics of integrons in Staphylococcus aureus resistance

Comprehensive profiling of antibiotic resistance genes and functional clusters of orthologous groups annotation of gut microbiota in Indonesian Kedu chickens

Antibiotic resistance is a growing global health concern, with poultry systems acting as important reservoirs of antibiotic resistance genes (ARGs). However, resistome and functional profiles of indigenous chickens raised under traditional systems remain underexplored. This study aimed to characterize the antibiotic resistome, virulence factor genes, and metabolic potential of gut microbiota in Indonesian Kedu chickens using a shotgun metagenomic approach. Digesta samples from five gastrointestinal segments of 21 healthy adult chickens were analyzed through high-throughput sequencing. ARGs were identified using the Comprehensive Antibiotic Resistance Database (CARD) and Antibiotic Resistance Genes Databases (ARDB), while virulence factors and functional genes were annotated using Virulence Factor Database (VFDB), Clusters of Orthologous Groups (COG), and Carbohydrate-Active EnZymes (CAZy) databases. Results revealed a diverse resistome dominated by multidrug resistance and efflux pump mechanisms, with prominent genes associated with fluoroquinolone, tetracycline, β-lactam, and glycopeptide resistance. The detection of clinically relevant ARGs suggests that genetic determinants associated with antimicrobial resistance are present in the gut microbiota of traditionally raised Kedu chickens, although metagenomic data alone cannot determine whether these genes are actively expressed or confer phenotypic resistance. Virulence factor analysis showed functions related to adherence, immune evasion, iron acquisition, quorum sensing, and efflux activity, reflecting strong microbial adaptability. Functional profiling demonstrated enrichment in translation, carbohydrate and amino acid metabolism, genome maintenance, and cell envelope biogenesis. Additionally, CAZyme analysis indicated a high capacity for complex polysaccharide degradation, supporting efficient utilization of fiber-rich traditional diets. In conclusion, this study provides a comprehensive metagenomic overview of antibiotic resistance and functional potential in Kedu chicken gut microbiota, emphasizing the importance of incorporating indigenous poultry into antimicrobial resistance surveillance within a One Health framework.

Bioorganic strategies for quorum sensing inhibition: disrupting biofilms and virulence in drug-resistant pathogens.

The escalating global crisis of antimicrobial resistance (AMR) poses a severe threat to public health, with bacterial biofilms and virulence factors exacerbating treatment failures in drug-resistant pathogens. Quorum sensing (QS), a density-dependent communication system, orchestrates biofilm formation, virulence expression, and resistance mechanisms in clinically relevant bacteria, including Pseudomonas aeruginosa, Staphylococcus aureus, and other pathogenic bacteria. Unlike conventional antibiotics, which exert selective pressure that can lead to resistance, QS inhibition offers a promising anti-virulence strategy by attenuating pathogenicity without directly killing bacteria. This review focuses on bioorganic approaches to QS disruption, encompassing natural products, synthetic analogues, hybrid phytocompound-nanoparticle conjugates, and metal-organic frameworks (MOFs). Key sections explore QS systems in Gram-negative and Gram-positive pathogens; molecular mechanisms of inhibition, including autoinducer synthesis blockade, receptor antagonism, and enzymatic degradation; structure-activity relationships (SAR), with emphasis on pharmacophores such as hydroxyl groups and α,β-unsaturated carbonyls; and evidence of biofilm and virulence attenuation in drug-resistant strains from in vitro, ex vivo, and in vivo studies. Synergistic effects with sub-MIC antibiotics are also highlighted, alongside challenges related to bioavailability, toxicity, and regulatory hurdles. Prospects include bioorthogonal probes for QS tracking, machine learning-aided design of next-generation inhibitors, nanoparticle-mediated targeted delivery, and emerging preclinical candidates. By leveraging advances in bioorganic chemistry, QS inhibition holds substantial translational potential for the management of AMR-driven infections and may redefine future therapeutic paradigms in infectious disease control.