Characterization of phage resistance and phages capable of intestinal decolonization of carbapenem-resistant Klebsiella pneumoniae in mice.
Characterization of phage resistance and phages capable of intestinal decolonization of carbapenem-resistant Klebsiella pneumoniae in mice.
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DOI：
10.1038/s42003-022-03001-y
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发表时间：
2022-01-13
影响因子：
5.9
通讯作者：
Zong Z
中科院分区：
文献类型：
--
作者：
Fang Q;Feng Y;McNally A;Zong Z
耐碳青霉烯肺炎克雷伯菌（CRKP）已成为严重的全球卫生挑战。我们分离并鉴定了两种以前未识别的裂解噬菌体P24和P39，它们具有大爆发大小，对ST11 KL64（一种主要的CRKP谱系）具有活性。P24和P39分别代表Przondovirus属（Studiervirinae亚科）和Webervirus属（drexlervirridae科）的种。P24和P39共同抑制CRKP生长近8 h。噬菌体抗性突变体表现出荚膜产量减少和毒力下降。编码荚膜多糖合成的mshA和wcaJ基因突变介导P24抗性，编码胞外多糖合成的epsJ基因突变引起P39抗性。我们用小鼠肠道定植模型测试了P24单独和与P39一起去定植CRKP的能力。P24和P39处理小鼠细菌负荷明显减少。总之，我们报道了两种先前未知的抗CRKP的裂解噬菌体的特性，揭示了噬菌体的耐药机制，并证明了裂解噬菌体在肠道非定殖方面的潜力。Fang等人发现了两种以前未发现的噬菌体，它们可以抑制碳青霉烯耐药肺炎克雷伯菌（CRKP）的生长并降低其毒力。他们还表明，CRKP产生了噬菌体耐药性，但在小鼠肠道定植模型中仍然可以去定植，这突出了噬菌体治疗是对抗耐药病原体的潜在治疗方法。
Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a severe global health challenge. We isolate and characterize two previously unidentified lytic phages, P24 and P39, with large burst sizes active against ST11 KL64, a major CRKP lineage. P24 and P39 represent species of the genera Przondovirus (Studiervirinae subfamily) and Webervirus (Drexlerviridae family), respectively. P24 and P39 together restrain CRKP growth to nearly 8 h. Phage-resistant mutants exhibit reduced capsule production and decreased virulence. Modifications in mshA and wcaJ encoding capsule polysaccharide synthesis mediate P24 resistance whilst mutations in epsJ encoding exopolysaccharide synthesis cause P39 resistance. We test P24 alone and together with P39 for decolonizing CRKP using mouse intestinal colonization models. Bacterial load shed decrease significantly in mice treated with P24 and P39. In conclusion, we report the characterization of two previously unidentified lytic phages against CRKP, revealing phage resistance mechanisms and demonstrating the potential of lytic phages for intestinal decolonization. Fang et al. characterized two previously unidentified phage species that could inhibit growth and decrease virulence of carbapenem-resistant Klebsiella pneumoniae (CRKP). They also showed that CRKP develop phage resistance but could still be decolonized in a mouse intestinal colonization model, highlighting phage therapy as potential treatment against drug-resistant pathogens.
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影响因子：
4.8
作者：
Kęsik-Szeloch A;Drulis-Kawa Z;Weber-Dąbrowska B;Kassner J;Majkowska-Skrobek G;Augustyniak D;Lusiak-Szelachowska M;Zaczek M;Górski A;Kropinski AM
通讯作者：
Kropinski AM
影响因子：
4.6
作者：
Hsu CR;Liao CH;Lin TL;Yang HR;Yang FL;Hsieh PF;Wu SH;Wang JT
通讯作者：
Wang JT
影响因子：
5.2
作者：
León M;Bastías R
通讯作者：
Bastías R
DOI：
10.1073/pnas.73.9.3303
发表时间：
1976-01-01
影响因子：
11.1
作者：
KURN, N;SHAPIRO, L
通讯作者：
SHAPIRO, L
DOI：
10.3390/v8120324
发表时间：
2016-12-01
期刊：
Viruses
影响因子：
--
作者：
Majkowska-Skrobek G;Łątka A;Berisio R;Maciejewska B;Squeglia F;Romano M;Lavigne R;Struve C;Drulis-Kawa Z
通讯作者：
Drulis-Kawa Z