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Cell. Infect. Microbiol."],"abstract":"<jats:p>The zoonotic pathogen <jats:italic>Bartonella henselae<\/jats:italic> is responsible for diverse human diseases, from mild to life-threatening, but it often eludes detection in culture-based assays. This study investigates the potential of <jats:italic>B. henselae<\/jats:italic> to enter a viable but nonculturable (VBNC) state when exposed to human fever temperature or antibiotics, with this state confirmed by successful resuscitation. Viability was assessed using SYBR Green I\/PI staining and propidium monoazide\u2013quantitative polymerase chain reaction (PMA-qPCR), while culturability was determined through colony-forming unit (CFU) counting on blood agar plates. Resuscitation of VBNC cells was attempted using modified Schneider\u2019s medium with 10% defibrillated sheep blood. In the results, <jats:italic>B. henselae<\/jats:italic> cells entered a VBNC state after 19 days of exposure to 38.8\u00b0C. Antibiotics, particularly with bactericidal activity, induced the VBNC state within 4 days treatment. Successful resuscitation confirmed the VBNC state developed via the above two strategies. Transmission electron microscopy (TEM) examination revealed intact cell structures and dense cytosol in VBNC cells, with a significant increase in plasmolytic cells. Notably, VBNC cells demonstrated greater drug tolerance than cells in the stationary phase, which encompassed a substantial portion of persisters. Proteomic analysis revealed the up-regulation of proteins linked to host cell invasion and stress resistance, while proteins related to signaling and cellular processes were down-regulated. Fluorescence <jats:italic>in situ<\/jats:italic> hybridization (FISH) analysis confirmed that the VBNC state truly boosted <jats:italic>B. henselae<\/jats:italic>\u2019s invasion of HUVECs. This study highlights <jats:italic>B. henselae<\/jats:italic>\u2019s capacity to enter a VBNC state under thermal and antibiotic stress, emphasizing the urgent need for advanced diagnostic and therapeutic strategies to effectively target VBNC cells, which complicate diagnosis and treatment.<\/jats:p>","DOI":"10.3389\/fcimb.2024.1486426","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T14:15:08Z","timestamp":1732198508000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Viable but nonculturable state in the zoonotic pathogen Bartonella henselae induced by low-grade fever temperature and antibiotic treatment"],"prefix":"10.3389","volume":"14","author":[{"given":"Yuze","family":"Gou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongxia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxian","family":"Xin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Xi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuanjie","family":"Che","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4194","DOI":"10.1128\/IAI.00404-15","article-title":"Viable but nonculturable and persister cells coexist stochastically and are induced by human serum","volume":"83","author":"Ayrapetyan","year":"2015","journal-title":"Infect. 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