{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:45:40Z","timestamp":1792197940762,"version":"4.4.0"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Intratumoral\n                    <jats:italic>Staphylococcus xylosus<\/jats:italic>\n                    enhances the ability of breast cancer cells to survive mechanical shear stress, a critical barrier encountered during hematogenous metastasis. However, the bacterial determinants underlying this effect remain unclear. Here, we identify the bacterial molecular chaperone DnaK as a key factor enabling\n                    <jats:italic>S. xylosus<\/jats:italic>\n                    to promote shear-stress tolerance in a human breast cancer cell line. Deletion of\n                    <jats:italic>dnaK<\/jats:italic>\n                    did not affect bacterial adhesion to or invasion of MDA-MB-231 cells but significantly reduced sustained intracellular survival. Under oxidative and acidic stress conditions, the \u0394\n                    <jats:italic>dnaK<\/jats:italic>\n                    mutant showed reduced survival compared with the wild-type strain, and its ability to enhance tumor-cell viability under shear stress was markedly impaired. Using a breast cancer\u2013on\u2013a\u2013chip microfluidic model, we demonstrate that infection with wild-type or complemented\n                    <jats:italic>Staphylococcus xylosus<\/jats:italic>\n                    confers increased tumor-cell viability under laminar shear stress in a time-dependent manner, whereas cells infected with the \u0394\n                    <jats:italic>dnaK<\/jats:italic>\n                    mutant fail to acquire shear-stress resistance and resemble uninfected controls. Together, these findings establish DnaK-dependent intracellular persistence of\n                    <jats:italic>S. xylosus<\/jats:italic>\n                    as a critical determinant of tumor-cell survival under mechanical stress, linking a conserved bacterial stress-response protein to cancer cell biomechanics in a metastasis-relevant context.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0341069","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T18:33:53Z","timestamp":1768934033000},"page":"e0341069","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["DnaK supports intracellular persistence of Staphylococcus xylosus and confers mechanical resilience to a human breast cancer cell line"],"prefix":"10.1371","volume":"21","author":[{"given":"Lei","family":"Ye","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guozheng","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0065-2386","authenticated-orcid":true,"given":"Lijuan","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"issue":"3","key":"pone.0341069.ref001","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"H Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"issue":"4","key":"pone.0341069.ref002","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/s41591-022-01779-2","article-title":"Targeting the gut and tumor microbiota in cancer","volume":"28","author":"EM Park","year":"2022","journal-title":"Nat Med"},{"issue":"21","key":"pone.0341069.ref003","article-title":"Microbiota in tumors: from understanding to application","volume":"9","author":"Y Xie","year":"2022","journal-title":"Adv Sci (Weinh)"},{"issue":"6","key":"pone.0341069.ref004","doi-asserted-by":"crossref","first-page":"109893","DOI":"10.1016\/j.isci.2024.109893","article-title":"Unveiling the intratumoral microbiota within cancer landscapes","volume":"27","author":"S Che","year":"2024","journal-title":"iScience"},{"issue":"4","key":"pone.0341069.ref005","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2019.07.008","article-title":"Tumor microbiome diversity and composition influence pancreatic cancer outcomes","volume":"178","author":"E Riquelme","year":"2019","journal-title":"Cell"},{"issue":"6356","key":"pone.0341069.ref006","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1126\/science.aah5043","article-title":"Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine","volume":"357","author":"LT Geller","year":"2017","journal-title":"Science"},{"issue":"6494","key":"pone.0341069.ref007","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1126\/science.aay9189","article-title":"The human tumor microbiome is composed of tumor type-specific intracellular bacteria","volume":"368","author":"D Nejman","year":"2020","journal-title":"Science"},{"issue":"1","key":"pone.0341069.ref008","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s42826-023-00169-0","article-title":"Staphylococcus xylosus and Staphylococcus aureus as commensals and pathogens on murine skin","volume":"39","author":"M Battaglia","year":"2023","journal-title":"Lab Anim Res"},{"issue":"7476","key":"pone.0341069.ref009","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nature12655","article-title":"Staphylococcus \u03b4-toxin induces allergic skin disease by activating mast cells","volume":"503","author":"Y Nakamura","year":"2013","journal-title":"Nature"},{"issue":"1","key":"pone.0341069.ref010","doi-asserted-by":"crossref","first-page":"6348","DOI":"10.1038\/s41598-017-05740-z","article-title":"The resident pathobiont Staphylococcus xylosus in Nfkbiz-deficient skin accelerates spontaneous skin inflammation","volume":"7","author":"Y Kim","year":"2017","journal-title":"Sci Rep"},{"issue":"8","key":"pone.0341069.ref011","article-title":"Tumor-resident intracellular microbiota promotes metastatic colonization in breast cancer","volume":"185","author":"A Fu","year":"2022","journal-title":"Cell"},{"key":"pone.0341069.ref012","doi-asserted-by":"crossref","first-page":"694012","DOI":"10.3389\/fmolb.2021.694012","article-title":"The Hsp70-chaperone machines in bacteria","volume":"8","author":"MP Mayer","year":"2021","journal-title":"Front Mol Biosci"},{"issue":"11","key":"pone.0341069.ref013","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/s41580-019-0133-3","article-title":"The Hsp70 chaperone network","volume":"20","author":"R Rosenzweig","year":"2019","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"5","key":"pone.0341069.ref014","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1006\/jmbi.1997.1072","article-title":"The power stroke of the DnaK\/DnaJ\/GrpE molecular chaperone system","volume":"269","author":"EV Pierpaoli","year":"1997","journal-title":"J Mol Biol"},{"key":"pone.0341069.ref015","doi-asserted-by":"crossref","first-page":"3162","DOI":"10.1099\/mic.0.2007\/009506-0","article-title":"Role for dnaK locus in tolerance of multiple stresses in Staphylococcus aureus","volume":"153","author":"VK Singh","year":"2007","journal-title":"Microbiology (Reading)"},{"issue":"3","key":"pone.0341069.ref016","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1128\/IAI.72.3.1364-1373.2004","article-title":"The DnaK\/DnaJ chaperone machinery of Salmonella enterica serovar Typhimurium is essential for invasion of epithelial cells and survival within macrophages, leading to systemic infection","volume":"72","author":"A Takaya","year":"2004","journal-title":"Infect Immun"},{"issue":"3","key":"pone.0341069.ref017","article-title":"The DnaK\/DnaJ chaperone system enables RNA polymerase-DksA complex formation in Salmonella experiencing oxidative stress","volume":"12","author":"J-S Kim","year":"2021","journal-title":"mBio"},{"issue":"11","key":"pone.0341069.ref018","doi-asserted-by":"crossref","first-page":"5065","DOI":"10.3390\/ijms26115065","article-title":"The role of Helicobacter pylori heat shock proteins in gastric diseases\u2019 pathogenesis","volume":"26","author":"OM Manna","year":"2025","journal-title":"Int J Mol Sci"},{"issue":"1","key":"pone.0341069.ref019","doi-asserted-by":"crossref","first-page":"14411","DOI":"10.1038\/s41598-018-32799-z","article-title":"Comparison of immunogenicity and vaccine efficacy between heat-shock proteins, HSP70 and GrpE, in the DnaK operon of Mycobacterium tuberculosis","volume":"8","author":"WS Kim","year":"2018","journal-title":"Sci Rep"},{"issue":"33","key":"pone.0341069.ref020","doi-asserted-by":"crossref","first-page":"18697","DOI":"10.1021\/acs.jafc.4c04627","article-title":"EnvZ\/OmpR controls protein expression and modifications in Cronobacter sakazakii for virulence and environmental resilience","volume":"72","author":"X Ji","year":"2024","journal-title":"J Agric Food Chem"},{"issue":"7","key":"pone.0341069.ref021","article-title":"DnaK-mediated protein deamidation: a potential mechanism for virulence and stress adaptation in Cronobacter sakazakii","volume":"89","author":"P Lu","year":"2023","journal-title":"Appl Environ Microbiol"},{"key":"pone.0341069.ref022","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1146\/annurev-biochem-060208-092442","article-title":"Molecular chaperone functions in protein folding and proteostasis","volume":"82","author":"YE Kim","year":"2013","journal-title":"Annu Rev Biochem"},{"key":"pone.0341069.ref023","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1201\/9781351120388-13","article-title":"Molecular mechanisms of Listeria monocytogenes stress responses.","volume-title":"Molecular food microbiology","author":"A Al\u00eda","year":"2021"},{"issue":"3","key":"pone.0341069.ref024","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.molcel.2004.12.027","article-title":"Severe oxidative stress causes inactivation of DnaK and activation of the redox-regulated chaperone Hsp33","volume":"17","author":"J Winter","year":"2005","journal-title":"Mol Cell"},{"issue":"3","key":"pone.0341069.ref025","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.gendis.2021.02.005","article-title":"Mechanism and effect of stress granule formation in cancer and its potential roles in breast cancer therapy","volume":"9","author":"T Hu","year":"2021","journal-title":"Genes Dis"},{"key":"pone.0341069.ref026","doi-asserted-by":"crossref","first-page":"745394","DOI":"10.3389\/fcell.2021.745394","article-title":"Stress granules involved in formation, progression and metastasis of cancer: a scoping review","volume":"9","author":"MR Asadi","year":"2021","journal-title":"Front Cell Dev Biol"},{"issue":"5","key":"pone.0341069.ref027","doi-asserted-by":"crossref","first-page":"4646","DOI":"10.3390\/cimb46050282","article-title":"Oxidative stress in breast cancer: a biochemical map of reactive oxygen species production","volume":"46","author":"LV Bel\u2019skaya","year":"2024","journal-title":"Curr Issues Mol Biol"},{"issue":"7","key":"pone.0341069.ref028","doi-asserted-by":"crossref","first-page":"3693","DOI":"10.1128\/IAI.01882-05","article-title":"Stress wars: the direct role of host and bacterial molecular chaperones in bacterial infection","volume":"74","author":"B Henderson","year":"2006","journal-title":"Infect Immun"},{"issue":"9","key":"pone.0341069.ref029","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.3390\/microorganisms8091351","article-title":"Mycoplasmas-host interaction: mechanisms of inflammation and association with cellular transformation","volume":"8","author":"F Benedetti","year":"2020","journal-title":"Microorganisms"},{"key":"pone.0341069.ref030","doi-asserted-by":"crossref","first-page":"678697","DOI":"10.3389\/fmolb.2021.678697","article-title":"Stress-responsive periplasmic chaperones in bacteria","volume":"8","author":"H Kim","year":"2021","journal-title":"Front Mol Biosci"},{"issue":"4","key":"pone.0341069.ref031","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.3390\/ijms21041311","article-title":"Role of mycoplasma chaperone DnaK in cellular transformation","volume":"21","author":"F Benedetti","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"51","key":"pone.0341069.ref032","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1815660115","article-title":"Mycoplasma promotes malignant transformation in vivo, and its DnaK, a bacterial chaperone protein, has broad oncogenic properties","volume":"115","author":"D Zella","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"17","key":"pone.0341069.ref033","doi-asserted-by":"crossref","first-page":"6402","DOI":"10.3390\/ijms21176402","article-title":"Gut microbiota and intestinal trans-epithelial permeability","volume":"21","author":"B Allam-Ndoul","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"1","key":"pone.0341069.ref034","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41392-022-01304-4","article-title":"Intratumoral microbiota: roles in cancer initiation, development and therapeutic efficacy","volume":"8","author":"L Yang","year":"2023","journal-title":"Signal Transduct Target Ther"},{"issue":"6161","key":"pone.0341069.ref035","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1126\/science.1240527","article-title":"Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment","volume":"342","author":"N Iida","year":"2013","journal-title":"Science"},{"key":"pone.0341069.ref036","doi-asserted-by":"crossref","first-page":"2989","DOI":"10.3389\/fimmu.2019.02989","article-title":"Gut microbiome as a potential factor for modulating resistance to cancer immunotherapy","volume":"10","author":"L Shui","year":"2020","journal-title":"Front Immunol"},{"issue":"12","key":"pone.0341069.ref037","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1038\/bjc.2014.348","article-title":"Immune modulation for cancer therapy","volume":"111","author":"J Naidoo","year":"2014","journal-title":"Br J Cancer"},{"issue":"3","key":"pone.0341069.ref038","article-title":"Bacterial heat shock protein activity","volume":"10","author":"F Maleki","year":"2016","journal-title":"J Clin Diagn Res"},{"issue":"8","key":"pone.0341069.ref039","doi-asserted-by":"crossref","first-page":"107948","DOI":"10.1101\/pdb.prot107948","article-title":"Allelic-exchange procedure in Staphylococcus aureus","volume":"2023","author":"MS Zeden","year":"2023","journal-title":"Cold Spring Harb Protoc"},{"issue":"10","key":"pone.0341069.ref040","doi-asserted-by":"crossref","DOI":"10.1128\/spectrum.00602-24","article-title":"Development of an inducer-free, virulence gene promoter-controlled, and fluorescent reporter-labeled CRISPR interference system in Staphylococcus aureus","volume":"12","author":"R Miah","year":"2024","journal-title":"Microbiol Spectr"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0341069","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T18:34:00Z","timestamp":1768934040000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0341069"}},"subtitle":[],"editor":[{"given":"Shih-Chao","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1,20]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0341069","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,20]]}}}