A Novel Bacteriophage with Broad Host Range against Clostridioides difficile Ribotype 078 Supports SlpA as the Likely Phage Receptor.
A Novel Bacteriophage with Broad Host Range against Clostridioides difficile Ribotype 078 Supports SlpA as the Likely Phage Receptor.
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DOI：
10.1128/spectrum.02295-21
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发表时间：
2022-02-23
影响因子：
3.7
通讯作者：
Minton NP
中科院分区：
文献类型：
--
作者：
Whittle MJ;Bilverstone TW;van Esveld RJ;Lücke AC;Lister MM;Kuehne SA;Minton NP
噬菌体是治疗艰难梭状芽胞杆菌(以前的艰难梭菌)感染(CDI)的一个有前途的选择，目前依赖于传统的抗生素治疗。噬菌体的特异性应该可以防止与CDI抗生素治疗相关的结肠微生物区系的失调。虽然已分离出大量噬菌体，但没有一个噬菌体对PCRribotype(RT)078菌株具有广泛的宿主范围活性，尽管它们与医药和农业相关。在这项研究中，我们分离到了四种新的艰难梭菌肌肉病毒：ΦCD08011，ΦCD418，ΦCD1801和ΦCD2301。它们的特性表明，除了ΦCD1801外，每个噬菌体都可以与文献中描述的其他艰难梭菌噬菌体相媲美，CD1801对RT078具有广泛的宿主活性，感染了15/16(93.8%)的测试菌株。为了利用野生型噬菌体有效地治疗CDI，必须组装一种最佳的噬菌体鸡尾酒，以提供对所有艰难梭菌RTS的广泛覆盖。我们进行了实验，以支持先前的发现，即艰难梭菌表层(S层)的一个成分SLpA可能是噬菌体受体。通过噬菌体结合试验，我们的数据表明，SLPACD1801只有在与RT078中发现的Φ等位基因相对应的质粒携带的S层盒存在的情况下，才能与RT012株结合。有了这些信息，应该努力分离具有广泛宿主范围活性的噬菌体，使其具有明确的S层盒类型，这可能形成有效治疗CDI的噬菌体鸡尾酒的基础。近年来，由于对抗菌素耐药性的日益关注，对噬菌体疗法的重要性研究出现了复苏。针对艰难梭状芽胞杆菌感染(CDI)的潜在治疗方法的噬菌体研究仍处于初级阶段，尚未得出最佳的“一刀切”的噬菌体鸡尾酒。到目前为止，这项研究的目标是找到寄主范围最广的噬菌体。然而，对于属于某些聚合酶链式反应核糖型(RTS)的艰难梭菌，特别是RT078，具有广泛宿主范围活性的噬菌体尚未被发现。在这项研究中，我们分离到了四种新的肌病毒，包括ΦCD1801，它对RT078具有最广泛的宿主范围活性。通过ΦCD1801在噬菌体结合分析中的应用，我们提供了数据支持先前的概念，即SLPA代表细菌细胞表面可能的噬菌体受体。我们的发现将研究重点引向了对具有明确S层盒类型的菌株具有活性的噬菌体的分离。
Bacteriophages represent a promising option for the treatment of Clostridioides difficile (formerly Clostridium difficile) infection (CDI), which at present relies on conventional antibiotic therapy. The specificity of bacteriophages should prevent dysbiosis of the colonic microbiota associated with antibiotic treatment of CDI. While numerous phages have been isolated, none have been characterized with broad host range activity toward PCR ribotype (RT) 078 strains, despite their relevance to medicine and agriculture. In this study, we isolated four novel C. difficile myoviruses: ΦCD08011, ΦCD418, ΦCD1801, and ΦCD2301. Their characterization revealed that each was comparable with other C. difficile phages described in the literature, with the exception of ΦCD1801, which exhibited broad host range activity toward RT 078, infecting 15/16 (93.8%) of the isolates tested. In order for wild-type phages to be exploited in the effective treatment of CDI, an optimal phage cocktail must be assembled that provides broad coverage against all C. difficile RTs. We conducted experiments to support previous findings suggesting that SlpA, a constituent of the C. difficile surface layer (S-layer) is the likely phage receptor. Through interpretation of phage-binding assays, our data suggested that ΦCD1801 could bind to an RT 012 strain only in the presence of a plasmid-borne S-layer cassette corresponding to the slpA allele found in RT 078. Armed with this information, efforts should be directed toward the isolation of phages with broad host range activity toward defined S-layer cassette types, which could form the basis of an effective phage cocktail for the treatment of CDI. IMPORTANCE Research into phage therapy has seen a resurgence in recent years owing to growing concerns regarding antimicrobial resistance. Phage research for potential therapy against Clostridioides difficile infection (CDI) is in its infancy, where an optimal “one size fits all” phage cocktail is yet to be derived. The pursuit thus far has aimed to find phages with the broadest possible host range. However, for C. difficile strains belonging to certain PCR ribotypes (RTs), in particular RT 078, phages with broad host range activity are yet to be discovered. In this study, we isolate four novel myoviruses, including ΦCD1801, which exerts the broadest host range activity toward RT 078 reported in the literature. Through the application of ΦCD1801 to phage-binding assays, we provide data to support the prior notion that SlpA represents the likely phage receptor on the bacterial cell surface. Our finding directs research attention toward the isolation of phages with activity toward strains possessing defined S-layer cassette types.
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影响因子：
17.1
作者：
Kirk JA;Gebhart D;Buckley AM;Lok S;Scholl D;Douce GR;Govoni GR;Fagan RP
通讯作者：
Fagan RP
影响因子：
4.8
作者：
Fagan, Robert P.;Fairweather, Neil F.
通讯作者：
Fairweather, Neil F.
影响因子：
4.9
作者：
Nale JY;Spencer J;Hargreaves KR;Buckley AM;Trzepiński P;Douce GR;Clokie MR
通讯作者：
Clokie MR
影响因子：
3.2
作者：
Mayer, Melinda J.;Narbad, Arjan;Gasson, Michael J.
通讯作者：
Gasson, Michael J.
影响因子：
5.2
作者：
Phothichaisri, Wichuda;Ounjai, Puey;Chankhamhaengdecha, Surang
通讯作者：
Chankhamhaengdecha, Surang