Potato common scab is a soil-borne disease caused mainly by Streptomyces scabies that seriously affects tuber quality and production. To understand the potential molecular mechanisms of potato tuber responded to common scab, a comparative proteomics approach was applied to analyze the proteome alteration of tuber skin and flesh after infected with common scab by two-dimensional gel electrophoresis (2-DE). Quantitative image analysis showed that the abundance of 36 and 26 protein spots in tuber skin and flesh of scab-infected potato were significantly altered (p < 0.05) more than 1.5-fold, respectively. All these differentially abundant proteins were successfully identified by MALDI-TOF/TOF MS, which were mainly involved in defense, bioenergy and metabolism, storage, chaperones, redox homeostasis, miscellaneous and other unknown functions. Compared with tuber flesh, more defense-related proteins were up-regulated in tuber skin, and several cell wall reorganization and lignification-related enzymes were also up-regulated in tuber skin. It appeared that the tuber skin as a barrier might be enriched with components of defense response to prevent the further infection of pathogen into tuber flesh. Several chaperones were up-regulated in tuber skin and flesh, suggesting a key role in reconstructing normal protein conformation and cell homeostasis in tubers. Conversely, common scab causes the down-regulation of many patatin proteins, which might inhibit tuber swelling. This study would provide some new insight into the potential response mechanisms of tuber infected with common scab, and help in developing strategies to improve resistance to common scab in potato breeding. • This study first investigated the potential proteomic dynamics in common scab-infected potato tuber skin and flesh. • The tuber skin as a barrier might be enriched with defensive components to prevent the further infection of pathogen into tuber flesh. • The storage protein accumulation of common scab-infected tuber was inhibited, which might further inhibit tuber swelling. • It will provide some references for the explanation of S. scabies infection process, and further develop strategies to improve common scab resistance in potato breeding. [ABSTRACT FROM AUTHOR]