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We describe herein a time\u2010resolved chemical proteomics strategy enabling host and pathogen temporal interaction profiling (HAPTIP) for tracking the entry of a pathogen into the host cell. A novel multifunctional chemical proteomics probe was introduced to label living bacteria followed by in\u2005vivo crosslinking of bacteria proteins to their interacting host\u2010cell proteins at different time points initiated by UV for label\u2010free quantitative proteomics analysis. We observed over 400 specific interacting proteins crosslinked with the probe during the formation of <jats:italic>Salmonella<\/jats:italic>\u2010containing vacuole (SCV). This novel chemical proteomics approach provides a temporal interaction profile of host and pathogen in high throughput and would facilitate better understanding of the infection process at the molecular level.<\/jats:p>","DOI":"10.1002\/anie.201911078","type":"journal-article","created":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T16:21:47Z","timestamp":1574785307000},"page":"2235-2240","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Tracking Pathogen Infections by Time\u2010Resolved Chemical Proteomics"],"prefix":"10.1002","volume":"59","author":[{"given":"Ying","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Biochemistry Department of Chemistry Center for Cancer Research Purdue University  West Lafayette IN 47907 USA"},{"name":"Minghang Hospital and Institutes of Biomedical Sciences Fudan University  131 Dong'an Road Shanghai 200032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Der\u2010Shyang","family":"Kao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Department of Chemistry Center for Cancer Research Purdue University  West Lafayette IN 47907 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Purdue University  West Lafayette IN 47907 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajdeep","family":"Bomjan","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Purdue University  West Lafayette IN 47907 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayank","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Department of Chemistry Center for Cancer Research Purdue University  West Lafayette IN 47907 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojie","family":"Lu","sequence":"additional","affiliation":[{"name":"Minghang Hospital and Institutes of Biomedical Sciences Fudan University  131 Dong'an Road Shanghai 200032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daoguo","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Purdue University  West Lafayette IN 47907 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5535-5517","authenticated-orcid":false,"given":"W. 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