A biomimetic proteomic approach for capturing and identifying S. mutans potential adhesion proteins via probiotic membrane-modified nanoparticles

Streptococcus mutans ( S . mutans ) is the primary etiological agent of dental caries. Probiotic therapy, such as with Lactobacillus acidophilus ( L . acidophilus ), represents a promising strategy for caries prevention, partly through co-aggregation with S . mutans via bacterial surface adhesins. However, the specific S . mutans adhesion proteins bound by probiotics remain largely unexplored due to challenges including undefined bait proteins, high background noise, and complex membrane structures. We developed a biomimetic proteomic nanoplatform that integrates L . acidophilus membrane-modified nanoparticles with quantitative proteomics to capture and identify S . mutans potential surface adhesion proteins. This platform enables high-throughput, affinity-based enrichment without predefined bait proteins. Using this approach, we identified several known adhesion-related proteins alongside previously undefined candidates. These findings were validated through subsequent gene knockout and pull-down experiments. This study innovatively combines membrane-modified nanotechnology with quantitative proteomics to elucidate interbacterial potential adhesion proteins. The established platform provides a novel methodological approach for investigating bacterial effector proteins and bacteria-bacteria interactions.