研究結果表明，利福霉素在亞MIC水平下能通過脫莢膜作用顯著增強傷寒沙門氏菌的細菌清除，這一作用機制對于治療MDR/XDR傷寒沙門氏菌及其它莢膜細菌具有重要意義。

近年來，全球范圍內耐藥菌的威脅日益嚴峻，尤其是多重耐藥（MDR）和廣泛耐藥（XDR）菌株的出現，給抗感染治療帶來了巨大挑戰。以傷寒沙門氏菌（S. Typhi）為例，這種細菌是引起傷寒熱的罪魁禍首，每年在全球范圍內導致超過15萬人死亡，尤其在南亞、東南亞和撒哈拉以南非洲地區更為嚴重。據WHO數據顯示，MDR和XDR傷寒沙門氏菌菌株的傳播已成為公共衛生領域的重大威脅，更為棘手的是，這些耐藥菌株對多種抗生素不敏感，這就使得傳統治療方法效果大打折扣。

近日，一篇發表在國際雜志eBioMedicine上題為“Rifampin mediated decapsulation and enhanced bacterial clearance: a new mechanism of rifamycins”的研究報告中，來自康奈爾大學獸醫學院等機構的科學家們通過研究深入探討了利福霉素如何通過脫莢膜機制來增強對細菌的清除，這就為耐藥菌的治療提供了新的策略。

這項研究中，研究人員揭示了利福霉素對傷寒沙門氏菌的獨特作用機制，相關研究發現不僅對于治療MDR/XDR傷寒沙門氏菌具有重要意義，還可能為其它莢膜細菌的治療開辟新途徑。研究者選取了24,206株傷寒沙門氏菌臨床分離株作為研究對象，通過全基因組測序（WGS）分析其抗生素耐藥基因特征，同時還使用了人原代中性粒細胞和小鼠感染模型來評估利福霉素脫莢膜作用對細菌清除的影響。

文中所采用的技術和材料：

全基因組測序（WGS）?：用于分析傷寒沙門氏菌臨床分離株的抗生素耐藥基因。

分子生物學和細胞生物學技術?：包括RT-qPCR、RNA測序、免疫印跡等，用于研究利福霉素對傷寒沙門氏菌莢膜合成基因表達的影響。

小鼠感染模型?：用于評估利福霉素脫莢膜作用在體內對細菌清除的增強效果。

人原代中性粒細胞?：用于研究利福霉素脫莢膜作用對細菌吞噬和活性氧爆發（ROS）的影響。

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傷寒沙門氏菌臨床分離株對利福霉素敏感，而在亞MIC水平下則可使傷寒沙門氏菌脫莢膜。

實驗流程：

WGS分析?：對24,206株傷寒沙門氏菌臨床分離株進行WGS，分析其抗生素耐藥基因特征，發現絕大多數傷寒沙門氏菌菌株對利福霉素敏感。

利福霉素脫莢膜作用研究?：在亞最小抑菌濃度（MIC）下，利福霉素能夠消除傷寒沙門氏菌的保護性莢膜Vi，這一過程稱為“脫莢膜”。通過免疫印跡和RNA測序等技術，發現利福霉素在轉錄水平上抑制莢膜合成基因的表達。

小鼠感染模型實驗?：利用Cmah null小鼠感染模型，評估利福霉素脫莢膜作用在體內對細菌清除的增強效果。結果顯示，利福霉素處理組小鼠的存活率顯著提高，且組織中的細菌載量顯著降低。

人原代中性粒細胞實驗?：研究利福霉素脫莢膜作用對傷寒沙門氏菌吞噬和ROS爆發的影響。發現脫莢膜后的傷寒沙門氏菌更易被中性粒細胞吞噬，并引發更強的ROS爆發。

研究結果表明，利福霉素在亞MIC水平下能通過脫莢膜作用顯著增強傷寒沙門氏菌的細菌清除，這一作用機制對于治療MDR/XDR傷寒沙門氏菌及其它莢膜細菌具有重要意義；此外，利福霉素作為FDA批準的藥物，易于獲取且安全性高。綜上，本文研究揭示了利福霉素通過脫莢膜作用增強細菌清除的新機制，為耐藥菌的治療提供了新的視角和策略。