Fu Songzhe, Octavia Sophie, Wang Qinning, Tanaka Mark M, Tay Chin Yen, Sintchenko Vitali, Lan Ruiting
School of Biotechnology and Biomolecular Sciences, University of New South Wales (UNSW) Sydney, NSW, Australia.
Centre for Infectious Diseases and Microbiology-Public Health, Institute of Clinical Pathology and Medical Research, Westmead Hospital Sydney, NSW, Australia.
Front Microbiol. 2016 Dec 26;7:2002. doi: 10.3389/fmicb.2016.02002. eCollection 2016.
serovar Typhimurium is the most common serovar causing human infections in Australia and many other countries. A total of 12,112 . Typhimurium isolates from New South Wales were analyzed by multi-locus variable number of tandem repeat (VNTR) analysis (MLVA) using five VNTRs from 2007 to 2014. We found that mid ranges of repeat units of 8-14 in VNTR locus STTR5, 6-13 in STTR6, and 9-12 in STTR10 were always predominant in the population (>50%). passaging experiments using MLVA type carrying extreme length alleles found that the majority of long length alleles mutated to short ones and short length alleles mutated to longer ones. Both data suggest directional mutability of VNTRs toward mid-range repeats. Sequencing of 28 isolates from a newly emerged MLVA type and its five single locus variants revealed that single nucleotide variation between isolates with up to two MLVA differences ranged from 0 to 12 single nucleotide polymorphisms (SNPs). However, there was no relationship between SNP and VNTR differences. A population genetic model of the joint distribution of VNTRs and SNPs variations was used to estimate the mutation rates of the two markers, yielding a ratio of 1 VNTR change to 6.9 SNP changes. When only one VNTR repeat difference was considered, the majority of pairwise SNP difference between isolates were 4 SNPs or fewer. Based on this observation and our previous findings of SNP differences of outbreak isolates, we suggest that investigation of . Typhimurium community outbreaks should include cases of 1 repeat difference to increase sensitivity. This study offers new insights into the short-term VNTR evolution of . Typhimurium and its application for epidemiological typing.
鼠伤寒血清型是澳大利亚和许多其他国家引起人类感染的最常见血清型。2007年至2014年期间，使用5个可变数目串联重复序列（VNTR），通过多位点可变数目串联重复序列分析（MLVA）对来自新南威尔士州的总共12112株鼠伤寒分离株进行了分析。我们发现，VNTR位点STTR5中重复单元为8 - 14的中等范围、STTR6中为6 - 13以及STTR10中为9 - 12的情况在群体中总是占主导地位（>50%）。使用携带极长等位基因的MLVA类型进行传代实验发现，大多数长等位基因突变为短等位基因，短等位基因突变为更长的等位基因。这两个数据都表明VNTR向中等范围重复序列的定向突变性。对一种新出现的MLVA类型及其五个单一位点变体的28株分离株进行测序显示，MLVA差异最多为两个的分离株之间的单核苷酸变异范围为0至12个单核苷酸多态性（SNP）。然而，SNP与VNTR差异之间没有关系。使用VNTR和SNP变异联合分布的群体遗传模型来估计这两个标记的突变率，得出1个VNTR变化对应6.9个SNP变化的比例。当仅考虑一个VNTR重复差异时，分离株之间的大多数成对SNP差异为4个SNP或更少。基于这一观察结果以及我们之前关于暴发分离株SNP差异的发现，我们建议对鼠伤寒社区暴发的调查应包括1个重复差异的病例，以提高敏感性。本研究为鼠伤寒的短期VNTR进化及其在流行病学分型中的应用提供了新的见解。
