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In vitro<\/jats:italic>\n                      experiments demonstrated that PTX potently inhibits intraerythrocytic development of drug-sensitive and -resistant strains, including chloroquine-resistant and artemisinin-resistant parasite lines, with 72-h half-maximal inhibitory concentrations (IC\u2085\u2080) ranging from 83.67 to 92.75 nM. PTX arrests parasite schizogony and reduces merozoite formation by ~25.69% to 37.46% when exposed to the trophozoite\/schizont stage. Meanwhile, time-dependent drug activity against gametocyte maturation demonstrated that treatment during the immature gametocyte stages elicited a significant reduction in final gametocytemia (~38.24% to 58.79%), thereby validating the dual-targeting potential of PTX against both the pathogenic asexual and transmission-competent sexual parasite stages. Molecular dynamics simulations suggested that PTX was capable of binding to\n                      <jats:italic toggle=\"yes\">P. falciparum<\/jats:italic>\n                      \u03b2-tubulin and potentially induced structural perturbations, including complex stabilization, enhanced M-loop flexibility, and global compaction, which may, in turn, disrupt microtubule dynamics. These results provide a plausible molecular basis for the antimalarial mechanism of PTX. Critically, PTX exhibits robust synergism with dihydroartemisinin (DHA) against artemisinin-resistant strains, reducing ring-stage survival to 1% and addressing the global challenge of artemisinin resistance.\n                      <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                      assays revealed that the PTX-DHA combination achieves near-complete parasite clearance (&lt;1% parasitemia) and 100% survival in rodent models and suppresses parasitemia by &gt;96% in humanized\n                      <jats:italic toggle=\"yes\">P. falciparum<\/jats:italic>\n                      models. This finding confirms PTX\u2019s translational potential and positions it as a novel tubulin-targeting partner for DHA, offering a promising strategy to combat drug-resistant malaria while safeguarding the efficacy of artemisinin-based combination therapies.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>In the current landscape of next-generation antimalarial development, preference will be given to compounds with activity against emerging drug-resistant parasite strains. However, identifying such effective molecules through traditional diversity library screenings remains challenging. As a result, the repurposing of old drugs has emerged as a prevalent and pragmatic strategy in the search for novel antimalarial agents. Our findings highlight a significant enhancement in combinatorial therapeutic efficacy, positioning paclitaxel as a promising partner drug for overcoming emerging drug resistance in malaria parasites. Therefore, we believe that this work will confer a broad interest to the readers of different disciplines, including antimalarial development.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01957-25","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T13:01:46Z","timestamp":1777554106000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Paclitaxel-induced tubulin dysfunction stalls parasite development: synergistic potential with artemisinin against resistant strains"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2252-2539","authenticated-orcid":false,"given":"Yongxin","family":"Tang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01czqbr06","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Global Health, School of Public Health, Nanjing Medical University","place":["Nanjing, China"]},{"id":[{"id":"https:\/\/ror.org\/01d176154","id-type":"ROR","asserted-by":"publisher"}],"name":"National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases","place":["Wuxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01czqbr06","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Global Health, School of Public Health, Nanjing Medical University","place":["Nanjing, China"]},{"id":[{"id":"https:\/\/ror.org\/01d176154","id-type":"ROR","asserted-by":"publisher"}],"name":"National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases","place":["Wuxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"He","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01d176154","id-type":"ROR","asserted-by":"publisher"}],"name":"National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases","place":["Wuxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1427-4793","authenticated-orcid":false,"given":"Tao","family":"Jiang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00angvn73","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5298-9234","authenticated-orcid":true,"given":"Jun","family":"Cao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01czqbr06","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Global Health, School of Public Health, Nanjing Medical University","place":["Nanjing, China"]},{"id":[{"id":"https:\/\/ror.org\/01d176154","id-type":"ROR","asserted-by":"publisher"}],"name":"National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases","place":["Wuxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1339-3558","authenticated-orcid":true,"given":"Xinyu","family":"Yu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01d176154","id-type":"ROR","asserted-by":"publisher"}],"name":"National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases","place":["Wuxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","unstructured":"World Health Organization. 2025. 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