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Our previous research found that <jats:italic>Mycoplasma fermentans<\/jats:italic> DnaK, a chaperone protein, impairs p53 activities, which are essential for most anti-cancer chemotherapeutic responses.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>To investigate the role of DnaK in chemotherapy, we treated cancer cell lines with <jats:italic>M. fermentans<\/jats:italic> DnaK and then with commonly used p53-dependent anti-cancer drugs (cisplatin and 5FU). We evaluated the cells\u2019 survival in the presence or absence of a DnaK-binding peptide (ARV-1502). We also validated our findings using primary tumor cells from a novel DnaK knock-in mouse model. To provide a broader context for the clinical significance of these findings, we investigated human primary cancer sequencing datasets from The Cancer Genome Atlas (TCGA). We identified <jats:italic>F. nucleatum<\/jats:italic> as a CAB carrying DnaK with an amino acid composition highly similar to <jats:italic>M. fermentans<\/jats:italic> DnaK. Therefore, we investigated the effect of <jats:italic>F. nucleatum<\/jats:italic> DnaK on the anti-cancer activity of cisplatin and 5FU.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Our results show that both <jats:italic>M. fermentans<\/jats:italic> and <jats:italic>F. nucleatum<\/jats:italic> DnaKs reduce the effectiveness of cisplatin and 5FU. However, the use of ARV-1502 effectively restored the drugs' anti-cancer efficacy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our findings offer a practical framework for designing and implementing novel personalized anti-cancer strategies by targeting specific bacterial DnaKs in patients with poor response to chemotherapy, underscoring the potential for microbiome-based personalized cancer therapies.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12967-024-05078-x","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T18:02:11Z","timestamp":1710266531000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Bacterial DnaK reduces the activity of anti-cancer drugs cisplatin and 5FU"],"prefix":"10.1186","volume":"22","author":[{"given":"Francesca","family":"Benedetti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel F.","family":"Mongodin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan H.","family":"Badger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arshi","family":"Munawwar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Cellini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weirong","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovannino","family":"Silvestri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl N.","family":"Kraus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Marini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chozha V.","family":"Rathinam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Salemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Tettelin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Gallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5576-5770","authenticated-orcid":false,"given":"Davide","family":"Zella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,12]]},"reference":[{"issue":"6494","key":"5078_CR1","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1126\/science.aay9189","volume":"368","author":"D Nejman","year":"2020","unstructured":"Nejman D, et al. 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