Yu Hyun J, Cha Da S R, Shin Dong-Hun, Nair Gopinath B, Kim Eun J, Kim Dong W
Department of Pharmacy, College of Pharmacy, Hanyang University, Ansan, South Korea.
Institute of Pharmacological Research, Hanyang University, Ansan, South Korea.
Front Microbiol. 2018 Mar 7;9:339. doi: 10.3389/fmicb.2018.00339. eCollection 2018.
Toxigenic strains arise upon infection and integration of the lysogenic cholera toxin phage, the CTX phage, into bacterial chromosomes. The serogroup O1 strains identified to date can be broadly categorized into three main groups: the classical biotype strains, which harbor CTX-cla; the prototype El Tor strains (Wave 1 strains), which harbor CTX-1; and the atypical El Tor strains, which harbor CTX-2 (Wave 2 strains) or CTX-3~6 (Wave 3 strains). The efficiencies of replication and transmission of CTX phages are similar, suggesting the possibility of existence of more diverse bacterial strains harboring various CTX phages and their arrays in nature. In this study, a set of strains was constructed by the chromosomal integration of CTX phages into strains that already harbored CTX phages or those that did not harbor any CTX phage or RS1 element. Strains containing repeats of the same kind of CTX phage, strains containing the same kind of CTX phage in each chromosome, strains containing alternative CTX phages in one chromosome, or containing different CTX phages in each chromosome have been constructed. Thus, strains with any CTX array can be designed and constructed. Moreover, the strains described in this study contained the -139F allele, which enhances the expression of TcpA and cholera toxin. These characteristics are considered to be important for cholera vaccine development. Once their capacity to provoke immunity in human against infection is evaluated, some of the generated strains could be developed further to yield cholera vaccine strains.
产毒菌株是在溶原性霍乱毒素噬菌体（CTX噬菌体）感染并整合到细菌染色体后产生的。迄今为止鉴定出的O1血清群菌株大致可分为三大类：携带CTX-cla的经典生物型菌株；携带CTX-1的原型埃尔托菌株（第1波菌株）；以及携带CTX-2（第2波菌株）或CTX-3至6（第3波菌株）的非典型埃尔托菌株。CTX噬菌体的复制和传播效率相似，这表明自然界中可能存在更多携带各种CTX噬菌体及其排列的不同细菌菌株。在本研究中，通过将CTX噬菌体染色体整合到已经携带CTX噬菌体的菌株或不携带任何CTX噬菌体或RS1元件的菌株中，构建了一组菌株。构建了含有同一种CTX噬菌体重复序列的菌株、每条染色体中含有同一种CTX噬菌体的菌株、一条染色体中含有交替CTX噬菌体的菌株或每条染色体中含有不同CTX噬菌体的菌株。因此，可以设计和构建具有任何CTX排列的菌株。此外，本研究中描述的菌株含有-139F等位基因，该等位基因可增强TcpA和霍乱毒素的表达。这些特性被认为对霍乱疫苗的开发很重要。一旦评估了它们在人体中激发抗感染免疫力的能力，一些产生的菌株可以进一步开发以产生霍乱疫苗菌株。
