Editorial: Deciphering Antimicrobial Resistance: Genetic Insights and Perspectives

Massimiliano Lucidi^1*Mattia Pirolo²Daniela Visaggio¹Valerio Baldelli³

• ¹Universita degli Studi Roma Tre Dipartimento di Scienze, Rome, Italy
• ²Kobenhavns Universitet, Copenhagen, Denmark
• ³Universita degli Studi di Milano, Milan, Italy

Antimicrobial agents have propelled medicine into the era of modern healthcare. However, the efficacy of antimicrobial therapies is progressively weakening as antimicrobial resistance (AMR) escalates, representing a profound threat to global health that transcends human, veterinary, and environmental boundaries. The development of AMR arises from multiple drivers, including i) antimicrobial overuse and misuse, ii) insufficient diagnostic practices, and iii) the intrinsic adaptability of microbial genomes. As AMR continues to spread, our ability to combat common infections and undertake routine medical interventions safely is increasingly compromised [1]. Addressing this challenge requires comprehensive research into the genetic basis of resistance mechanisms, surveillance of microbial communities across multiple reservoirs, and the development of novel strategies to counteract AMR [2].The collection presented in Frontiers in Cellular and Infection Microbiology provides a comprehensive view of the genetic determinants, epidemiology, and functional consequences of AMR across clinical, veterinary, and environmental settings. These studies highlight the need for One Health strategies, integrating surveillance and interventions across humans, animals, and the environment to curb the global spread of AMR.In veterinary settings, the study of AMR reveals both environmental and human-mediated pathways for the dissemination of resistant organisms. that Candida albicans can exhibit paradoxical growth under caspofungin exposure, a phenomenon in which fungal cells resume growth at drug concentrations above the minimum inhibitory concentration. This response is driven by activation of stress-response pathways coupled with segmental aneuploidy, which together confer reversible echinocandin resistance, illustrating how dynamically fungi can adapt their genomes under antimicrobial pressure. Intracellular lifestyle is one strategy some microbes use to evade antimicrobials. In this context, Bao et al. offered a lysosome-centered view of Mycobacterium tuberculosis pathogenesis, revealing intracellular survival strategies that indirectly influence therapeutic efficacy and potentially contribute to resistance development.Finally, longitudinal studies, such as that from Zhao et al., can provide an essential perspective to enhance our understanding of AMR evolution and population dynamics. Indeed, this study analysed the Serratia marcescens complex in ICU patients over 11 years, identifying inter-ICU transmission and the accumulation of β-lactamase and carbapenemase genes, highlighting the importance of continuous genomic surveillance Figure 1 highlights the valuable scientific contributions of this collection, exemplifying the breadth and depth of current AMR research. The studies demonstrate that resistance emerges through adaptation to intracellular lifestyle and diverse genetic mechanisms, including plasmid-mediated gene acquisition, point mutations, efflux operons, and genome-scale rearrangements. Surveillance across clinical, community, veterinary, and environmental reservoirs is indispensable to identify emerging threats, while mechanistic studies guide the development of targeted interventions. Additionally, the works highlight the importance of combining genomic, phenotypic, and epidemiological approaches to fully understand the evolution and fitness costs associated with resistance.Altogether, this collection underscores the urgent need for One Health approaches to combat AMR. It advocates investment in diagnostics, genomic surveillance, and strategies to limit its spread, as deepening our understanding of AMR sharpens surveillance and therapeutic precision while informing policies that bridge human, animal, and environmental health. By fostering interdisciplinary and mechanistic research, the field moves closer to preserving the effectiveness of antimicrobials that underpin modern medicine.