Comparative Genome Analysis of the Daptomycin-Resistant Streptococcus anginosus Strain J4206 Associated with Breakthrough Bacteremia.
Comparative Genome Analysis of the Daptomycin-Resistant Streptococcus anginosus Strain J4206 Associated with Breakthrough Bacteremia.
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DOI：
10.1093/gbe/evw241
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发表时间：
2016-12-31
影响因子：
3.3
通讯作者：
McShan WM
中科院分区：
文献类型：
--
作者：
Rahman M;Nguyen SV;McCullor KA;King CJ;Jorgensen JH;McShan WM
咽峡炎链球菌是正常口腔植物群的成员，其可成为引起人类化脓性感染的病原体。测定了达托霉素耐药菌株J 4206的基因组，该菌株最初是从圣安东尼奥的德克萨斯大学健康科学中心的一名患有突破性菌血症和脓毒性休克的患者中分离的。环状基因组长2，001，352 bp，GC含量为38.62%，包含多个移动的遗传元件，包括介导突变表型的噬菌体样染色体岛SanCI、转座子和整合接合元件。达托霉素耐药性涉及细胞膜和细胞壁的多种改变，在J 4206中发现了可能导致耐药性的独特特征。存在一簇用于胆碱代谢和转运的囊多糖（CPS）基因，可能有助于中和细胞表面电荷，从而使达托霉素结合不稳定。此外，存在编码分选酶和参与细胞壁修饰的LPXTG靶蛋白的独特J 4206基因。J 4206基因组在遗传学上与最近报道的万古霉素耐药SA 1菌株密切相关;然而，这些基因组与心磷脂合成酶、组氨酸激酶yycG、磷壁酸修饰基因和其他参与细胞表面修饰的基因中的SNP不同。透射电子显微镜显示，两个菌株J 4206和SA 1的细胞壁显着厚，更电子密度比达托霉素和万古霉素敏感菌株J 4211。这项比较基因组研究已经确定了J 4206基因组中参与细胞表面修饰的独特基因以及等位基因变体，因此可能有助于获得达托霉素耐药性。
Streptococcus anginosus is a member of the normal oral flora that can become a pathogen causing pyogenic infections in humans. The genome of daptomycin-resistant strain J4206, originally isolated from a patient suffering from breakthrough bacteremia and septic shock at the University of Texas Health Science Center at San Antonio, was determined. The circular genome is 2,001,352 bp long with a GC content of 38.62% and contains multiple mobile genetic elements, including the phage-like chromosomal island SanCI that mediates a mutator phenotype, transposons, and integrative conjugative elements. Daptomycin resistance involves multiple alterations in the cell membrane and cell wall, and unique features were identified in J4206 that may contribute to resistance. A cluster of capsular polysaccharide (CPS) genes for choline metabolism and transport are present that may help neutralize cell surface charges, destabilizing daptomycin binding. Further, unique J4206 genes encoding sortases and LPXTG-target proteins that are involved in cell wall modification were present. The J4206 genome is phylogenetically closely related to the recently reported vancomycin-resistant SA1 strain; however, these genomes differ with SNPs in cardiolipin synthetase, histidine kinase yycG, teichoic acid modification genes, and other genes involved in cell surface modification. Transmission electron microscopy showed that the cell walls of both strains J4206 and SA1 were significantly thicker and more electron dense than daptomycin- and vancomycin-sensitive strain J4211. This comparative genomic study has identified unique genes as well as allelic variants in the J4206 genome that are involved in cell surface modification and thus might contribute to the acquisition of daptomycin resistance.
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影响因子：
14.9
作者：
Dhillon BK;Chiu TA;Laird MR;Langille MG;Brinkman FS
通讯作者：
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