Klebsiella quasipneumoniae is an opportunistic pathogen causing antibiotic-resistant infections of the gastrointestinal tract in many clinical cases. Orally delivered bioactive Klebsiella-specific antimicrobial proteins, klebicins, could be a promising method to eradicate Klebsiella species infecting the gut. Mouse infection model was established based on infection of antibiotic-treated BALB/C mice with K. quasipneumoniae strain DSM28212. Four study groups were used (3 animals/group) to test the antimicrobial efficacy of orally delivered klebicin KvarIa: vehicle-only group (control, phosphate-buffered saline), and other three groups with bacteria, antibiotic therapy and 100 µg of uncoated Kvarla, 100 µg coated KvarIa, 1000 µg coated-KvarIa. Because of the general sensitivity of bacteriocins to gastroduodenal proteases, Kvarla doses were coated with Eudragit®, a GMP-certified formulation agent that releases the protein at certain pH. The coating treatment was selected based on measurements of mouse GI tract pH. The quantity of Klebsiella haemolysin gene (khe) in faecal samples of the study animals was used to quantify the presence of Klebsiella. GI colonization of K. quasipneumoniae was achieved only in the antibiotic-treated mice groups. Significant changes in khe marker quantification were found after the use of Eudragit® S100 formulated klebicin KvarIa, at both doses, with a significant reduction of K. quasipneumoniae colonization compared to the vehicle-only control group. Mouse GI tract colonization with K. quasipneumoniae can be achieved if natural gut microbiota is suppressed by prior antibiotic treatment. The study demonstrates that GI infection caused by K. quasipneumoniae can be significantly reduced using Eudragit®-protected klebicin KvarIa.

中文翻译：

---

使用抗菌蛋白 KvarIa 减少类肺炎克雷伯菌的胃肠道定植

类肺炎克雷伯菌是一种机会性病原体，在许多临床病例中会引起胃肠道的抗生素耐药性感染。口服具有生物活性的克雷伯氏菌特异性抗菌蛋白 klebicins 可能是根除感染肠道的克雷伯氏菌的一种有前途的方法。基于类肺炎克雷伯菌菌株DSM28212感染抗生素处理的BALB/C小鼠建立小鼠感染模型。使用四个研究组（每组 3 只动物）来测试口服克莱比星 KvarIa 的抗菌效果：仅载体组（对照组，磷酸盐缓冲盐水）和其他三个使用细菌、抗生素治疗和 100 µg 未包衣 Kvarla 的组, 100 µg 包衣 KvarIa, 1000 µg 包衣-KvarIa。由于细菌素对胃十二指肠蛋白酶普遍敏感，Kvarla 剂量涂有 Eudragit®，这是一种 GMP 认证的制剂，可在特定 pH 值下释放蛋白质。基于小鼠胃肠道pH的测量选择涂层处理。研究动物粪便样本中克雷伯氏菌溶血素基因 (khe) 的数量用于量化克雷伯氏菌的存在。K. quasipneumoniae 的 GI 定植仅在抗生素治疗的小鼠组中实现。在两种剂量下使用 Eudragit® S100 配制的 klebicin KvarIa 后，发现 khe 标记定量发生了显着变化，与仅使用载体的对照组相比，类肺炎克雷伯菌定植显着减少。如果先前的抗生素治疗抑制了天然肠道微生物群，则可以实现小鼠胃肠道定植 K. quasipneumoniae。