2026-10-11T22:55:06Z https://www.scidb.cn/oai

10.57760/sciencedb.35019 2026-05-06T21:43:41Z

2026-05-06 Essential fatty acids disrupt the mycolic acid-rich cell envelope of clinical Nocardia isolates: A membrane-targeting approach to combat persistent infections doi:10.57760/sciencedb.35019 en Conventional antibiotics against slow‑growing, mycolic acid‑rich Nocardia often require prolonged therapy and are associated with high relapse rates. We evaluated five essential fatty acids (EFAs) against 82 clinical Nocardia isolates. α-Linolenic acid, γ-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid (DHA) exhibited comparable activity (MIC50 / MIC90: 31.25/62.50 μM), corresponding to mass concentration ranges of 8.7 to 10.3 μg/mL for MIC50 and 17.4 to 20.6 μg/mL for MIC90. However, arachidonic acid was markedly less active. Using DHA as a representative EFA, we showed that it rapidly disrupts the mycolic acid‑rich cell envelope, causing propidium iodide influx and ultrastructural damage, and achieves concentration‑dependent bactericidal killing within 1 h, a feat not observed with imipenem. Transcriptomic analysis revealed that surviving cells enter a state of metabolic sensitization, characterized by a maladaptive transcriptional response involving the downregulation of the proton-pumping Nuo complex, compensatory upregulation of the type II NADH dehydrogenase (Ndh), and a global induction of protein synthesis machinery. Critically, this DHA-induced disruption of the permeability barrier and metabolic reprogramming restored the efficacy of aminoglycosides; subinhibitory concentrations of DHA significantly potentiated amikacin activity against intrinsically resistant N. wallacei isolates (FICI: 0.51–0.56). These findings establish DHA as a dual-action agent that both kills Nocardia via membrane disruption and sensitizes persistent cells to co-administered antibiotics, offering a rational membrane-targeting strategy to combat recalcitrant mycolic acid-rich pathogens. essential fatty acids; Nocardia; mycolic acid; metabolic sensitization; aminoglycoside synergy Ming Wei Shiwang Xie Peng Wang Tianmeng Li Jun Liu Jingxian Yang Xinmin Xu Dan Luo Li Gu Shuai Wang PUBLIC https://creativecommons.org/licenses/by/4.0/ dataset Science Data Bank