Lee Grace C, Long S Wesley, Musser James M, Beres Stephen B, Olsen Randall J, Dallas Steven D, Nunez Yury O, Frei Christopher R
College of Pharmacy, The University of Texas at Austin, Austin, Texas; School of Medicine, The University of Texas Health Science Center, San Antonio, Texas.
Pharmacotherapy. 2015 Feb;35(2):220-8. doi: 10.1002/phar.1536. Epub 2015 Feb 3.
Our understanding of the molecular dynamics driving the community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) epidemic at the whole genome level is limited. We sought to assess the use of whole genome sequencing (WGS) to evaluate the genomic diversity and genotypic prediction of antimicrobial resistance of CA-MRSA isolates from patients in South Texas.
Comparative whole genome sequencing.
Thirteen clinical CA-MRSA isolates recovered from patients presenting with skin and soft tissue infections to nine primary care clinics in the South Texas Ambulatory Research Network between 2010 and 2013.
Comparative WGS was performed on the 13 MRSA sequence type 8 clinical isolates. We compared the resistome of genes encoding for antibiotic resistance with a phenotypically derived antibiogram using standard antimicrobial susceptibility testing. The strains differed by an average of 72 single nucleotide polymorphisms (SNPs) per isolate in the core genome compared with FPR3757 (USA300, reference strain). There were a total of 623 unique SNPs in the core genome (range 47-88 SNPs per isolate). We identified 19 nonsynonymous SNPs in genes encoding proven or putative S. aureus virulence determinants in the core genome. There was complete concordance between genotypic evidence for antimicrobial resistance and the phenotypically derived antibiogram.
Overall, although these CA-MRSA isolates were similar on the level of clonal type, clinical syndrome, and geographic area, the strains were diverse at the genome level. Furthermore, our findings provide important proof-of-concept information for using WGS as a potential front-end screening tool for antimicrobial resistance predictions.
我们对在全基因组水平上驱动社区获得性耐甲氧西林金黄色葡萄球菌(CA-MRSA)流行的分子动力学的理解有限。我们试图评估全基因组测序(WGS)在评估来自南德克萨斯州患者的CA-MRSA分离株的基因组多样性和抗菌药物耐药性的基因型预测方面的应用。
比较全基因组测序。
2010年至2013年间,从南德克萨斯门诊研究网络的9家初级保健诊所中,从患有皮肤和软组织感染的患者身上分离出13株临床CA-MRSA分离株。
对13株MRSA序列类型8临床分离株进行了比较WGS。我们使用标准抗菌药物敏感性测试,将编码抗生素耐药性的基因的耐药组与表型衍生的抗菌谱进行了比较。与FPR3757(USA300,参考菌株)相比,核心基因组中每个分离株平均有72个单核苷酸多态性(SNP)。核心基因组中共有623个独特的SNP(每个分离株范围为47-88个SNP)。我们在核心基因组中编码已证实或推定的金黄色葡萄球菌毒力决定因素的基因中鉴定出19个非同义SNP。抗菌药物耐药性的基因型证据与表型衍生的抗菌谱完全一致。
总体而言,尽管这些CA-MRSA分离株在克隆类型、临床综合征和地理区域水平上相似,但这些菌株在基因组水平上是多样的。此外,我们的研究结果为使用WGS作为抗菌药物耐药性预测的潜在前端筛选工具提供了重要的概念验证信息。