Faruque Shah M, Tam Vincent C, Chowdhury Nityananda, Diraphat Pornphan, Dziejman Michelle, Heidelberg John F, Clemens John D, Mekalanos John J, Nair G Balakrish
Molecular Genetics Laboratory, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka-1212, Bangladesh.
Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5151-6. doi: 10.1073/pnas.0700365104. Epub 2007 Mar 12.
Cholera outbreaks in subSaharan African countries are caused by strains of the El Tor biotype of toxigenic Vibrio cholerae O1. The El Tor biotype is the causative agent of the current seventh cholera pandemic, whereas the classical biotype, which was associated with the sixth pandemic, is now extinct. Besides other genetic differences the CTX prophages encoding cholera toxin in the two biotypes of V. cholerae O1 have distinct repressor (rstR) genes. However, recent incidences of cholera in Mozambique were caused by an El Tor biotype V. cholerae O1 strain that, unusually, carries a classical type (CTX(class)) prophage. We conducted genomic analysis of the Mozambique strain and its CTX prophage together with chromosomal phage integration sites to understand the origin of this atypical strain and its evolutionary relationship with the true seventh pandemic strain. These analyses showed that the Mozambique strain carries two copies of CTX(class) prophage located on the small chromosome in a tandem array that allows excision of the prophage, but the excised phage genome was deficient in replication and did not produce CTX(class) virion. Comparative genomic microarray analysis revealed that the strain shares most of its genes with the typical El Tor strain N16961 but did not carry the TLC gene cluster, and RS1 sequence, adjacent to the CTX prophage. Our data are consistent with the Mozambique strain's having evolved from a progenitor similar to the seventh pandemic strain, involving multiple recombination events and suggest a model for origination of El Tor strains carrying the classical CTX prophage.
撒哈拉以南非洲国家的霍乱疫情是由产毒性霍乱弧菌O1的埃尔托生物型菌株引起的。埃尔托生物型是当前第七次霍乱大流行的病原体，而与第六次大流行相关的古典生物型现已灭绝。除了其他基因差异外，霍乱弧菌O1的两种生物型中编码霍乱毒素的CTX噬菌体具有不同的阻遏物（rstR）基因。然而，莫桑比克最近的霍乱疫情是由一种埃尔托生物型霍乱弧菌O1菌株引起的，该菌株异常地携带一种古典类型（CTX(class)）噬菌体。我们对莫桑比克菌株及其CTX噬菌体以及染色体噬菌体整合位点进行了基因组分析，以了解这种非典型菌株的起源及其与真正的第七次大流行菌株的进化关系。这些分析表明，莫桑比克菌株在小染色体上以串联阵列形式携带两个CTX(class)噬菌体拷贝，这允许噬菌体切除，但切除的噬菌体基因组在复制方面存在缺陷，并且不产生CTX(class)病毒粒子。比较基因组微阵列分析显示，该菌株与典型的埃尔托菌株N16961共享其大部分基因，但不携带TLC基因簇以及与CTX噬菌体相邻的RS1序列。我们的数据与莫桑比克菌株从类似于第七次大流行菌株的祖先进化而来的观点一致，涉及多次重组事件，并提出了一个携带古典CTX噬菌体的埃尔托菌株起源的模型。
