中国福氏志贺菌优势序列型ST91获得SRL和Tn7多重耐药岛分析

Analysis of SRL and Tn7 multi-drug resistant islands acquired by dominant Shigella flexneri sequence type 91 isolated in China

目的分析中国福氏志贺菌优势序列型ST91(sequence type 91)中志贺菌耐药岛(Shigella resistance locus,SRL)和Tn7耐药岛的分布及变化情况。方法对包括14种血清型(1a[7株],1b[1株],1d[1株],2a[5株],2b[1株],3a[3株],3b[1株],4a[1株],4av[1株],4b[1株],X[9株],Xv[25株],Y[2株]和Yv[1株])和7种ST型(ST91[50株],ST109[1株],ST18[3株],ST142[1株],ST143[1株],ST103[2株],ST16[1株])的59株中国福氏志贺菌基因组中SRL、Tn7耐药岛的编码基因及核酸序列进行分析,并与参考菌株2002017和YSH600的SRL和Tn7岛进行比较。结果所有50株中国分离的福氏志贺菌ST91菌株,1株ST109和1株ST142菌株均携带SRL和Tn7岛。1株ST18菌株仅携带2个耐药岛的3个耐药基因。其他ST型菌株均未发现耐药岛。与参考菌株2002017相比,9株ST91菌株的SRL耐药岛发生了插入或缺失。其中,7株ST91菌株缺失了编码四环素耐药性的tet基因;1株ST91菌株缺失了编码β-内酰胺酶的oxa-1和编码氯霉素乙酰转移酶的cat基因;1株ST91的SRL岛上插入了1个编码广谱β-内酰胺酶的blaTEM-1基因。所有50株ST91、1株ST109和1株ST142菌株携带的Tn7岛的核酸序列和编码基因与参考菌株相比未发现差异。结论福氏志贺菌ST91型中国分离菌株均携带SRL和Tn7耐药岛。在SRL岛上发生了基因的插入和缺失。处于进化早期的ST18菌株,在获得耐药岛的过程中可能发挥了重要作用。

Objective To study the distributions and genetic variations of Shigella resistance locus （SRL） and Tn7 multi-drug resistant genomic islands in dominant Shigella flexneri sequence type 91 （ST91） isolated in China. Methods The SRL and Tn7 of draft genome sequences of 59 S. flexneri isolates were compared with published complete genomes of S. flexneri 2002017 and YSH600. These 59 isolates covered 14 serotypes （1a [7 isolates], 1b [ 1 isolate] , 1d [ 1 isolate], 2a [5 isolates], 2b[1 isolate], 3a [3 isolates], 3b [1 isolate], 4a [1 isolate], 4av [1 isolate] ,4b [1 isolate], X [9 isolates], Xv [25 isolates], Y [2 isolates] and Yv [ 1 isolate] ） and 7 STs （ST91 [50 isolates], ST109 [ 1 isolate ], ST18 [3 isolates], ST142[ 1 isolate], ST143 [ 1 isolate], ST103 [2 isolates] and STI6 [ 1 isolate] ）. Results All 50 ST91 isolates, 1 ST109 isolate and 1 ST142 isolate each carried the SRL and Tn7 multidrug resistant islands. 1 ST18 isolate carried only 3 resistant genes from two islands. The genes of the two resistant islands were not identified in the rest isolates. Insertion or deletions on SRL islands were observed in 9 ST91 isolate, as compared with genome of S. flexneri Xv 2002017, of which, 7 ST91 isolates deleted tetracycline resistance genes, 1 ST91 isolate deleted β-1actarnases oxa-1 gene and ehloramphenieol aeetyltransferase eat gene and 1 ST91 isolate had an insertion of β-laetamase bla bla TEM-1 gene. No sequence variation was observed for Tn7 islands for all draft genomes analyzed in this study. Conclusion All of S. flexneri ST91 isolates analyzed in this study carried SRL and Tn7 multi-drug resistant islands. Moreover, genetic variations such as deletions and insertion were observed on the SRL island. The ST18 might play an important role in acquiring and spreading of the two multi-drug resistant islands, which was phylogenetically ancient as compared with ST91.