Novel type of specialized transduction for CTXφ or its satellite phage RS1 mediated by filamentous phage VGJφ in Vibrio cholerae
Novel type of specialized transduction for CTXφ or its satellite phage RS1 mediated by filamentous phage VGJφ in Vibrio cholerae
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DOI：
10.1128/jb.185.24.7231-7240.2003
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发表时间：
2003-12-01
影响因子：
3.2
通讯作者：
Fando, R
中科院分区：
文献类型：
--
作者：
Campos, J;Martínez, E;Fando, R
霍乱毒素是霍乱弧菌的主要毒力因子，由溶原丝状噬菌体CTXphi基因组中含有的ctxAB操纵子编码。这种噬菌体在表达毒素协同调节菌毛（TCP），即CTXphi受体的霍乱弧菌群之间传播ctxAB基因。在研究ctxAB传播的新形式时，我们发现霍乱弧菌丝状噬菌体VGJphi以甘露糖敏感的血凝素（MSHA）菌毛为受体，通过一种高效且高度特异性的不依赖tcp的机制传播CTXphi或其卫星噬菌体RS1。这是一种新型的特化转导，包括VGJphi和CTXphi（或RS1）复制形式的位点特异性协整，以产生单个杂交分子，该分子产生单链DNA杂交基因组，该基因组被包装成称为hybphi（用于VGJphi/CTXphi杂交）和HybRSphi（用于VGJphi/RS1杂交）的杂交病毒颗粒。杂交噬菌体利用VGJphi复制功能和VGJphi衣壳进行复制，保留了通过MSHA感染的能力。即使在体外表达TCP的最佳条件下，杂交噬菌体感染大多数被测菌株的效率也高于CTXphi。霍乱弧菌1333减毒活疫苗株感染和溶菌作用可恢复毒力。我们的研究结果强化了TCP对于CTXphi的获取并不是必不可少的。因此，我们讨论了目前公认的霍乱弧菌新毒株出现的进化模型的替代方案，以及我们的发现对开发环境更安全的减毒霍乱活疫苗的重要性。
The main virulence factor of Vibrio cholerae, the cholera toxin, is encoded by the ctxAB operon, which is contained in the genome of the lysogenic filamentous phage CTXphi. This phage transmits ctxAB genes between V cholerae bacterial populations that express toxin-coregulated pilus (TCP), the CTXphi( receptor. In investigating new forms of ctxAB transmission, we found that V cholerae filamentous phage VGJphi, which uses the mannose-sensitive hemagglutinin (MSHA) pilus as a receptor, transmits CTXphi or its satellite phage RS1 by an efficient and highly specific TCP-independent mechanism. This is a novel type of specialized transduction consisting in the site-specific cointegration of VGJphi and CTXphi (or RS1) replicative forms to produce a single hybrid molecule, which generates a single-stranded DNA hybrid genome that is packaged into hybrid viral particles designated HybPphi (for the VGJphi/CTXphi hybrid) and HybRSphi (for the VGJphi/RS1 hybrid). The hybrid phages replicate by using the VGJphi replicating functions and use the VGJphi capsid, retaining the ability to infect via MSHA. The hybrid phages infect most tested strains more efficiently than CTXphi, even under in vitro optimal conditions for TCP expression. Infection and lysogenization with HybPphi revert the V. cholerae live attenuated vaccine strain 1333 to virulence. Our results reinforce that TCP is not indispensable for the acquisition of CTXphi. Thus, we discuss an alternative to the current accepted evolutionary model for the emergence of new toxigenic strains of V. cholerae and the importance of our findings for the development of an environmentally safer live attenuated cholera vaccine.