Antimicrobial resistance (AMR) is a significant global threat that affects not only human health but also the health of animals and the environment. The evolution and spread of AMR are driven by a complex set of interconnected factors across all domains of One Health. Effectively addressing this challenge requires systems approaches and collaborative efforts across multiple sectors. We conducted a systematic quantitative literature review to explore the application of systems thinking approaches in examining the factors driving AMR and their interactions across human, animal and environmental systems. Based on 21 selected studies, we developed a causal loop diagram to illustrate key contributing factors and their interrelationships influencing AMR and highlight the need for interventions that extend beyond antibiotic use. Our findings emphasise that reducing antibiotic use in a single system is insufficient to curb AMR. Instead, sustained reductions require a multifaceted approach, including stronger regulations, increased awareness of appropriate antibiotic prescribing and use, non-antimicrobial measures such as vaccination and infection control, and improved waste and wastewater treatment practices. Despite progress in understanding AMR, critical gaps remain in assessing how social determinants, human activities, and environmental factors contribute to its evolution and spread. Systems thinking has proven valuable in fostering a shared understanding of AMR, facilitating collaborative decision-making, and informing evidence-based policies. Engaging stakeholders in co-designing and evaluating interventions will be essential to advancing global efforts to mitigate AMR and achieve long-term, sustainable solutions.

The mecC gene conferring methicillin-resistance has always been found on a SCCmec type XI element and is largely restricted to the few clonal complexes CC130, CC1943, CC425, CC49 and CC599. The occurrence of the mecC gene in many different hosts highlighted its One Health importance, even though European hedgehogs (Erinaceus europaeus) are considered its natural reservoir, most probably because of the selective pressure imposed by beta-lactam-producing dermatophytes (Trichophyton erinacei) that colonize the skin of these mammals. Surprisingly, while the presence of T. erinacei on the French territory has been proven, no mecC-positive methicillin-resistant Staphylococcus aureus (MRSA) isolate has been reported yet from hedgehogs. We thus sampled 139 hedgehogs brought to a wildlife center; 128 were S. aureus carriers and 25 (18.0 %) presented a MRSA isolate, of which 21 (15.1 %) displayed the mecC gene. All 161 S. aureus collected were whole-genome sequenced. The mecC-MRSA belonged to the classical CCs, i.e. CC130, CC1943 and CC49. The majority (98/139, 70.5 %) of the methicillin-susceptible Staphylococcus aureus (MSSA) isolates also belonged to these three CCs. A phylogenetic comparison with mecC-MRSA isolates from all over Europe and New-Zealand showed local adaptations, despite the fact that they all belonged to the same CCs. The acquisition of the SCCmec type XI element by a concomitant MSSA could not be observed in the same animal, but such a transfer might be suggested since identical clones were identified, one MSSA and one MRSA, though in different animals. In parallel, we conducted a detailed analysis of the SCCmec type XI element as well as specific virulence factors (a tst variant and the vwbSaPI gene). Results led us to hypothesize that the mecC gene might be acquired through selective pressure of T. erinacei on MSSA, some of which were acquired a long time ago from ruminants and are now colonizing the skin of the hedgehogs.