{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:14:31Z","timestamp":1788455671937,"version":"build-2803163510"},"reference-count":56,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T00:00:00Z","timestamp":1651795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"China Key Scientific Grant Program","award":["2021YFC0122500"],"award-info":[{"award-number":["2021YFC0122500"]}]},{"name":"China Key Scientific Grant Program","award":["GWV-10.1-XK01"],"award-info":[{"award-number":["GWV-10.1-XK01"]}]},{"name":"China Key Scientific Grant Program","award":["201940300"],"award-info":[{"award-number":["201940300"]}]},{"name":"Shanghai Municipal health commission","award":["2021YFC0122500"],"award-info":[{"award-number":["2021YFC0122500"]}]},{"name":"Shanghai Municipal health commission","award":["GWV-10.1-XK01"],"award-info":[{"award-number":["GWV-10.1-XK01"]}]},{"name":"Shanghai Municipal health commission","award":["201940300"],"award-info":[{"award-number":["201940300"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The antibiotic resistance rates of Klebsiella pneumoniae have been steadily increasing in recent years. Nevertheless, the metabolic features of the drug-resistant Klebsiella pneumoniae and its associated benefits for bacterial pathogenicity are far from expounded. This study aims to unravel the unique physiological and metabolic properties specific to drug-resistant K. pneumoniae. Using scanning electron microscopy (SEM), we observed a thicker extracellular mucus layer around a drug-resistant K. pneumonia strain (Kp-R) than a drug-sensitive K. pneumonia strain (Kp-S). Kp-R also produced more capsular polysaccharide (CPS) and biofilm, and appeared to have a significant competitive advantage when co-cultured with Kp-S. Moreover, Kp-R was easier to adhere to and invade A549 epithelial cells than Kp-S but caused less cell-viability damage according to cell counting kit-8 (CCK-8) tests. Immunofluorescence revealed that both Kp-R and Kp-S infection destroyed the tight junctions and F-actin of epithelial cells, while the damage caused by Kp-S was more severe than Kp-R. We detected the extracellular metabolites secreted by the two strains with UHPLC-Q-TOF MS to explore the critical secretion products. We identified 16 predominant compounds that were differentially expressed. Among them, inosine increased the viability of epithelial cells in a dose-dependent manner, and an A2AR antagonist can abolish such enhancement. D-mannose, which was secreted less in Kp-R, inhibited the viability of A549 cells in the range of low doses. These findings provide potential targets and research strategies for preventing and treating drug-resistant K. pneumoniae infections.<\/jats:p>","DOI":"10.3390\/molecules27092994","type":"journal-article","created":{"date-parts":[[2022,5,8]],"date-time":"2022-05-08T21:31:20Z","timestamp":1652045480000},"page":"2994","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Inosine and D-Mannose Secreted by Drug-Resistant Klebsiella pneumoniae Affect Viability of Lung Epithelial Cells"],"prefix":"10.3390","volume":"27","author":[{"given":"Yuhan","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Pulmonary and Critical Care Medicine, Chinese People\u2019s Liberation Army General Hospital, Beijing 100853, China"},{"name":"Medical School of Chinese People\u2019s Liberation Army, Beijing 100853, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwei","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200437, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxuan","family":"Xiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200437, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200437, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Guan","sequence":"additional","affiliation":[{"name":"College of Pulmonary and Critical Care Medicine, Chinese People\u2019s Liberation Army General Hospital, Beijing 100853, China"},{"name":"Medical School of Chinese People\u2019s Liberation Army, Beijing 100853, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pulmonary and Critical Care Medicine, Chinese People\u2019s Liberation Army General Hospital, Beijing 100853, China"},{"name":"Medical School of Chinese People\u2019s Liberation Army, Beijing 100853, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farui","family":"Shu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200437, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1897-4415","authenticated-orcid":false,"given":"Jiaqi","family":"Shen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200437, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoyan","family":"Gu","sequence":"additional","affiliation":[{"name":"College of Pulmonary and Critical Care Medicine, Chinese People\u2019s Liberation Army General Hospital, Beijing 100853, China"},{"name":"Medical School of Chinese People\u2019s Liberation Army, Beijing 100853, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200437, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingzhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Centre for Clinical Laboratory, Shanghai 200126, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1091-2041","authenticated-orcid":false,"given":"Lixin","family":"Xie","sequence":"additional","affiliation":[{"name":"College of Pulmonary and Critical Care Medicine, Chinese People\u2019s Liberation Army General Hospital, Beijing 100853, China"},{"name":"Medical School of Chinese People\u2019s Liberation Army, Beijing 100853, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1128\/CMR.11.4.589","article-title":"Klebsiella spp. as Nosocomial Pathogens: Epidemiology, Taxonomy, Typing Methods, and Pathogenicity Factors","volume":"11","author":"Podschun","year":"1998","journal-title":"Clin. 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