Lysogenic conversion of environmental Vibrio mimicus strains by CTXΦ

Lysogenic conversion of environmental Vibrio mimicus strains by CTXΦ
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DOI:
10.1128/iai.67.11.5723-5729.1999
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发表时间:
1999-11-01
影响因子:
3.1
通讯作者:
Mekalanos, JJ
Mekalanos, JJ
中科院分区:
医学2区
文献类型:
--
作者:
Faruque, SM;Rahman, MM;Mekalanos, JJ

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已知丝状噬菌体CTX Phi(其编码霍乱弧菌中的霍乱毒素(CT))通过使用毒素共调节菌毛(TCP)作为其受体感染霍乱弧菌的敏感菌株而繁殖,从而引起来自非霍乱弧菌祖细胞的霍乱弧菌的新菌株的产生。除了霍乱弧菌之外,通常TCP阴性的拟态弧菌菌株也被证明偶尔产生CT并引起人类腹泻。我们分析了从孟加拉国地表沃茨分离的非产毒性拟态弧菌菌株对CTX Phi的敏感性和溶原性转化,并通过使用噬菌体的遗传标记衍生物研究了CT在溶原菌中的表达。在分析的27株拟态弧菌菌株中,其中2株(7.4%)被来源于SM 44(P27459 ctx::km)的CTX-Km Phi感染,噬菌体基因组整合到宿主染色体上,形成稳定的溶原菌。溶原菌在培养上清中自发产生感染性噬菌体颗粒,经丝裂霉素C诱导后,噬菌体滴度可达较高水平。这是第一次证明通过CTX Phi的拟态弧菌菌株的溶原性转化。当携带功能性ctxAB操纵子的CTX Phi基因组的复制形式的遗传标记衍生物pMSF9.2被引入非致炎性拟态弧菌菌株中时,质粒整合到宿主基因组中,并且菌株在体外和成年兔的肠内产生CT,并在兔中引起轻度至重度腹泻。这表明,在自然栖息地中,野生型CTX Phi对非产毒拟态弧菌菌株的感染可能导致能够产生生物活性CT的产毒拟态弧菌菌株的起源。本研究的结果还支持CTX Phi感染的TCP非依赖性机制的存在,并表明至少一种霍乱弧菌以外的弧菌可能有助于噬菌体的繁殖。
The filamentous bacteriophage CTX Phi, which encodes cholera toxin (CT) in toxigenic Vibrio cholerae, is known to propagate by infecting susceptible strains of V. cholerae by using the toxin coregulated pilus (TCP) as its receptor and thereby causing the origination of new strains of toxigenic V, cholerae from nontoxigenic progenitors. Besides V. cholerae, Vibrio mimicus strains which are normally TCP negative have also been shown to occasionally produce CT and cause diarrhea in humans, We analyzed nontoxigenic V, mimicus strains isolated from surface waters in Bangladesh for susceptibility and lysogenic conversion by CTX Phi, and studied the expression of CT in the lysogens by using genetically marked derivatives of the phage, Of 27 V. mimicus strains analyzed, which were all negative for genes encoding TCP but positive for the regulatory gene toxR, 2 strains (7.4%) were infected by CTX-Km Phi, derived from strain SM44(P27459 ctx::km), and the phage genome integrated into the host chromosome, forming stable lysogens, The lysogens spontaneously produced infectious phage particles in the supernatant fluids of the culture, and high titers of the phage could be achieved when the lysogens were induced with mitomycin C. This is the first demonstration of lysogenic conversion of V. mimicus strains by CTX Phi. When a genetically marked derivative of the replicative form of the CTX Phi genome carrying a functional ctxAB operon, pMSF9.2, was introduced into nontoxigenic V. mimicus strains, the plasmid integrated into the host genome and the strains produced CT both in vitro and inside the intestines of adult rabbits and caused mild-to-severe diarrhea in rabbits. This suggested that in the natural habitat infection of nontoxigenic V, mimicus strains by wild-type CTX Phi may lead to the origination of toxigenic V. mimicus strains which are capable of producing biologically active CT. The results of this study also supported the existence of a TCP-independent mechanism for infection by CTX Phi and showed that at least one species of Vibrio other than V. cholerae may contribute to the propagation of the phage.