Emerging zoonotic pathogen Staphylococcus borealis mediates longitudinal increase and environmental contamination of tigecycline resistance throughout the pig production period.

The widespread use of tetracyclines in swine production has accelerated the emergence of tigecycline-resistant Staphylococcus, posing a threat to public health. This study investigated the prevalence and mechanisms of tigecycline resistance in pigs, where tigecycline is unapproved yet resistance is present. The emerging zoonotic pathogen Staphylococcus borealis played an important role. Longitudinal surveillance revealed that tigecycline-resistant S. borealis (TRSB) ST64 colonized newborn piglets and persisted throughout the entire production period, exhibiting environmental contamination from feces to soil. Whole-genome sequencing analysis indicated that antimicrobial usage was reflected in the prevalence of antimicrobial-resistant genes (ARGs). Further mechanistic experiments elucidated that tigecycline resistance was conferred by S10 and Tet(L) variants. The tet(L)P257S variant conferred higher doxycycline resistance and cross-resistance to tigecycline, contributing to fitness advantages in host bacteria under tetracycline pressure. Phylogenetic analysis suggested the clonal expansion of TRSB ST64 drove the dissemination of tet(L)P257S. Moreover, tet(L)P257S was carried by two novel kinds of conjugative broad-host-range miniplasmids, which enable facilitating horizontal transfer between Staphylococcus and Enterococcus. Our findings emphasized the urgent necessity of antimicrobial-resistant surveillance and assessment in food animal production from the One Health perspective, particularly regarding the abuse and residues of veterinary antimicrobials developing cross-resistance to the "last-resort" drugs.