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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Using bioluminescence to monitor treatment response in real time in mice with Mycobacterium ulcerans infection.
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Using bioluminescence to monitor treatment response in real time in mice with Mycobacterium ulcerans infection.

机译：使用生物发光实时监测溃疡分枝杆菌感染小鼠的治疗反应。

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Mycobacterium ulcerans causes Buruli ulcer, a potentially disabling ulcerative skin disease. Only recently was antimicrobial therapy proven effective. Treatment for 2 months with rifampin plus streptomycin was first proposed after experiments in the mouse footpad model demonstrated bactericidal activity. This treatment is now considered the treatment of choice, although larger ulcers may require adjunctive surgery. Shorter, oral regimens are desired, but evaluating drug activity in mice is hampered by the very slow growth of M. ulcerans, which takes 3 months to produce countable colonies. We created a recombinant bioluminescent M. ulcerans strain expressing luxAB from Vibrio harveyi for real-time evaluation of antimicrobial effects in vivo. Mouse footpads were injected with wild-type M. ulcerans 1059 (WtMu) or the recombinant bioluminescent strain (rMu). Two weeks later, mice received rifampin plus streptomycin, kanamycin alone (to which rMu is resistant), or streptomycin alone for 4 weeks and were observed for footpad swelling (preventive model). Untreated controls and kanamycin-treated rMu-infected mice received rifampin plus streptomycin for 4 weeks after developing footpad swelling (curative model). Compared to WtMu, rMu exhibited similar growth and virulence in vivo and similar drug susceptibility. A good correlation was observed between luminescence (measured as relative light units) and number of viable bacteria (measured by CFU) in footpad homogenates. Proof of concept was also shown for serial real-time evaluation of drug activity in live mice. These results indicate the potential of bioluminescence as a real-time surrogate marker for viable bacteria in mouse footpads to accelerate the identification of new treatments for Buruli ulcer.
机译：溃疡分枝杆菌会引起布鲁氏溃疡，这是一种潜在的致残性溃疡性皮肤病。直到最近才证明抗菌治疗有效。在小鼠足垫模型中的实验证明具有杀菌活性后，首次提出用利福平加链霉素治疗2个月。尽管较大的溃疡可能需要辅助手术，但现在认为这种治疗是首选治疗。需要更短的口服方案，但是溃疡分枝杆菌非常缓慢的生长会妨碍评估小鼠的药物活性，这需要3个月才能产生可​​计数的菌落。我们创建了一个重组生物发光的M. ulcerans菌株，表达了来自哈维弧菌的luxAB，用于实时评估体内的抗菌作用。给小鼠脚垫注射野生型溃疡分支杆菌1059（WtMu）或重组生物发光菌株（rMu）。两周后，小鼠接受利福平加链霉素，单独的卡那霉素（对rMu耐药）或单独的链霉素治疗4周，并观察其足垫肿胀（预防模型）。未经治疗的对照和经卡那霉素治疗的rMu感染小鼠在出现足垫肿胀后（治疗性模型）接受了利福平加链霉素治疗4周。与WtMu相比，rMu在体内的生长和毒力相似，对药物的敏感性也相似。观察到脚垫匀浆中的发光（以相对光单位测量）与活菌数量（以CFU测量）之间具有良好的相关性。还显示了概念证明，可用于对活小鼠的药物活性进行系列实时评估。这些结果表明生物发光作为鼠标脚垫中活细菌的实时替代标志物的潜力，可加速鉴定Buruli溃疡的新疗法。

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