Abstract
The perianal skin is a unique "skin-gut" boundary that serves as a critical hotspot for the exchange and evolution of antibiotic resistance genes (ARGs). However, its role in the dissemination of antimicrobial resistance (AMR) has often been underestimated. To characterize the resistance patterns in the perianal skin environment of patients with perianal diseases and to investigate the drivers of AMR in this niche, a total of 51 bacterial isolates were selected from a historical strain bank containing isolates originally collected from patients with perianal diseases. All the isolates originated from the skin site and were subjected to antimicrobial susceptibility testing, whole-genome sequencing, and co-occurrence network analysis. The analysis revealed a highly structured resistance pattern, dominated by two distinct modules: one representing a classic Staphylococcal resistance platform centered around mecA and the bla operon, and a broad-spectrum multidrug resistance module in Gram-negative bacteria centered around tet(A) and predominantly carried by IncFIB and other IncF family plasmids. Further analysis pinpointed IncFIB-type plasmids as potent vehicles driving the efficient dissemination of the latter resistance module. Moreover, numerous unexplained resistance phenotypes were observed in a subset of isolates, indicating the potential presence of emerging and uncharacterized AMR threats. These findings establish the perianal skin as a complex reservoir of multidrug resistance genes and a hub for mobile genetic element exchange, highlighting the necessity of enhanced surveillance and targeted interventions in this clinically important ecological niche.