Impact of Phage CDHS-1 on the Transcription, Physiology and Pathogenicity of a Clostridioides difficile Ribotype 027 Strain, R20291.
Impact of Phage CDHS-1 on the Transcription, Physiology and Pathogenicity of a Clostridioides difficile Ribotype 027 Strain, R20291.
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DOI：
10.3390/v13112262
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发表时间：
2021-11-11
期刊：
影响因子：
--
通讯作者：
Clokie MRJ
中科院分区：
文献类型：
--
作者：
Nale JY;Al-Tayawi TS;Heaphy S;Clokie MRJ
所有已知的艰难梭菌均编码整合酶，使其潜在地能够裂解或溶源化细菌菌株。在此，我们观察了CDHS-1对核糖型027菌株R20291的感染，并确定了噬菌体和细菌基因表达谱，以及噬菌体感染对细菌生理和致病性的影响。使用RNA-seq和RT-qPCR，我们分析了在MOI为10的噬菌体复制的早期、中期和晚期期间的转录组学变化。噬菌体具有20分钟的潜伏期，需要80分钟裂解细胞，爆发大小为~37。所有噬菌体基因在至少一个时间点期间高度表达。Cro/C1-转录调节因子、ssDNA结合蛋白和解旋酶在早期表达，holin在对数中期表达，结构蛋白从对数中期到晚期表达。大多数细菌基因，特别是代谢和毒素产生/调节基因，从早期噬菌体复制下调。大蜡螟定殖期间，噬菌体抗性菌株和溶原菌的毒力降低，这可通过幼虫存活率以及生长（10）、繁殖（2）和感染（2）标记基因的表达来确定。这些数据表明，噬菌体感染既减少了定殖，又对细菌致病性产生了负面影响，为支持开发这种噬菌体用于治疗C.艰难感染
All known Clostridioides difficile phages encode integrases rendering them potentially able to lyse or lysogenise bacterial strains. Here, we observed the infection of the siphovirus, CDHS-1 on a ribotype 027 strain, R20291 and determined the phage and bacterial gene expression profiles, and impacts of phage infection on bacterial physiology and pathogenicity. Using RNA-seq and RT-qPCR we analysed transcriptomic changes during early, mid-log and late phases of phage replication at an MOI of 10. The phage has a 20 min latent period, takes 80 min to lyse cells and a burst size of ~37. All phage genes are highly expressed during at least one time point. The Cro/C1-transcriptional regulator, ssDNA binding protein and helicase are expressed early, the holin is expressed during the mid-log phase and structural proteins are expressed from mid-log to late phase. Most bacterial genes, particularly the metabolism and toxin production/regulatory genes, were downregulated from early phage replication. Phage-resistant strains and lysogens showed reduced virulence during Galleria mellonella colonization as ascertained by the larval survival and expression of growth (10), reproduction (2) and infection (2) marker genes. These data suggest that phage infection both reduces colonization and negatively impacts bacterial pathogenicity, providing encouraging data to support the development of this phage for therapy to treat C. difficile infection.
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预言对细菌病原体的进化和毒力的重要性。
影响因子：
5.2
作者：
Fortier LC;Sekulovic O
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影响因子：
4.4
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Kwon, Jennie H.;Olsen, Margaret A.;Dubberke, Erik R.
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DOI：
10.1073/pnas.1309739110
发表时间：
2013-07-16
影响因子：
11.1
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6.4
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3.2
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