The cyclic dinucleotide (CDN)-stimulator of interferon genes (STING) pathway plays an important role in the detection of viral and bacterial pathogens in animals. Previous studies have shown that the metazoan second messenger cyclic [G(2′,5′)pA(3′,5′)p] (2′,3′-cGAMP) generated by cyclic GMP-AMP synthase cGAS binds STING with high affinity compared with bacterial CDNs such as c-di-GMP, c-di-AMP, and 3′,3′-cGAMP. Despite recent progress indicating that the CDN-binding domain (CBD) of dimeric STING binds asymmetric 2′,3′-cGAMP preferentially over symmetric 3′,3′-CDNs, it remains an open question whether STING molecules, such as human STING, adopt a symmetric dimeric conformation to efficiently engage its asymmetric ligand. Here, structural studies of the CBD from porcine STING (STING^CBD) in complex with CDNs at 1.76–2.6 Å resolution revealed that porcine STING^CBD, unlike its human and mouse counterparts, can adopt an asymmetric ligand-binding pocket to accommodate the CDNs. We observed that the extensive interactions and shape complementarity between asymmetric 2′,3′-cGAMP and the ligand-binding pocket make it the most preferred ligand for porcine STING and that geometry constraints limit the binding between symmetric 3′,3′-CDN and porcine STING. The ligand-discrimination mechanism of porcine STING observed here expands our understanding of how the CDN–STING pathway is activated and of its role in antiviral defense.

To determine whether methicillin-susceptible S. aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) are present in commercial pig farms and food products from supermarkets in China, we characterized S. aureus isolates from 250 samples associated with swine and animal-related food products in Shandong Province. The isolates were characterized by susceptibility testing, toxin gene detection, pulse-field gel electrophoresis (PFGE), multilocus sequence typing, and spa typing. MRSA were identified and typed by the staphylococcal cassette chromosome mec (SCCmec). The prevalence of S. aureus among all samples was 19.6% (49/250). MRSA and MSSA accounted for 16.7% (20/120) and 8.3% (10/120), respectively, of swine feces samples. Only MSSA was detected from swine carcass, pork, chicken, and raw milk, accounting for 15% (6/40), 10% (3/30), 20% (6/30), and 13.3% (4/30), respectively. The predominant MRSA clone was ST9-t899 SCCmecIVb/PFGE A (70.0%, 14/20). Among the MSSA isolates, ST9-t899/PFGE A was the most prevalent (27.6%), followed by ST15-t084 (17.2%), ST97-t2756 (10.3%), ST1-t127 (6.9%), and ST398-t899 (3.5%). Some lineages were found that are commonly detected in humans (e.g., ST1, ST5, ST7, ST59, ST88) or are human-specific (e.g., ST15). The toxin genes sec, seh, and enterotoxin gene cluster (egc) were significantly more prevalent among isolates of lineage ST9 (p<0.001) compared to other lineages, and the ST9 isolates were more resistant to erythromycin, clindamycin, ciprofloxacin, chloramphenicol, and gentamicin. The same lineage was identified from different sample types, indicating circulation of the related strains within the area of study. In conclusion, swine and food products of animal origin carried S. aureus, and the predominant ST9 clone possesses a multidrug-resistance profile and a high prevalence of sec, seh, and egc enterotoxin genes.