de Man Tom J B, Limbago Brandi M
Centers for Disease Control and Prevention, Division of Healthcare Quality Promotion, Atlanta, Georgia, USA.
mSphere. 2016 Jan 13;1(1). doi: 10.1128/mSphere.00050-15. eCollection 2016 Jan-Feb.
We present the easy-to-use Sequence Search Tool for Antimicrobial Resistance, SSTAR. It combines a locally executed BLASTN search against a customizable database with an intuitive graphical user interface for identifying antimicrobial resistance (AR) genes from genomic data. Although the database is initially populated from a public repository of acquired resistance determinants (i.e., ARG-ANNOT), it can be customized for particular pathogen groups and resistance mechanisms. For instance, outer membrane porin sequences associated with carbapenem resistance phenotypes can be added, and known intrinsic mechanisms can be included. Unique about this tool is the ability to easily detect putative new alleles and truncated versions of existing AR genes. Variants and potential new alleles are brought to the attention of the user for further investigation. For instance, SSTAR is able to identify modified or truncated versions of porins, which may be of great importance in carbapenemase-negative carbapenem-resistant Enterobacteriaceae. SSTAR is written in Java and is therefore platform independent and compatible with both Windows and Unix operating systems. SSTAR and its manual, which includes a simple installation guide, are freely available from https://github.com/tomdeman-bio/Sequence-Search-Tool-for-Antimicrobial-Resistance-SSTAR-. IMPORTANCE Whole-genome sequencing (WGS) is quickly becoming a routine method for identifying genes associated with antimicrobial resistance (AR). However, for many microbiologists, the use and analysis of WGS data present a substantial challenge. We developed SSTAR, software with a graphical user interface that enables the identification of known AR genes from WGS and has the unique capacity to easily detect new variants of known AR genes, including truncated protein variants. Current software solutions do not notify the user when genes are truncated and, therefore, likely nonfunctional, which makes phenotype predictions less accurate. SSTAR users can apply any AR database of interest as a reference comparator and can manually add genes that impact resistance, even if such genes are not resistance determinants per se (e.g., porins and efflux pumps).
我们展示了易于使用的抗菌药物耐药性序列搜索工具SSTAR。它将针对可定制数据库的本地执行的BLASTN搜索与直观的图形用户界面相结合,用于从基因组数据中识别抗菌药物耐药性(AR)基因。虽然该数据库最初是从获得性耐药决定因素的公共存储库(即ARG-ANNOT)中填充的,但可以针对特定病原体组和耐药机制进行定制。例如,可以添加与碳青霉烯耐药表型相关的外膜孔蛋白序列,并纳入已知的固有机制。该工具的独特之处在于能够轻松检测现有AR基因的推定新等位基因和截短版本。变体和潜在的新等位基因会引起用户的注意,以便进一步研究。例如,SSTAR能够识别孔蛋白的修饰或截短版本,这在碳青霉烯酶阴性的碳青霉烯耐药肠杆菌科中可能非常重要。SSTAR是用Java编写的,因此与平台无关,并且与Windows和Unix操作系统都兼容。SSTAR及其手册(包括简单的安装指南)可从https://github.com/tomdeman-bio/Sequence-Search-Tool-for-Antimicrobial-Resistance-SSTAR-免费获取。重要性 全基因组测序(WGS)正迅速成为鉴定与抗菌药物耐药性(AR)相关基因的常规方法。然而,对于许多微生物学家来说,WGS数据的使用和分析带来了巨大挑战。我们开发了SSTAR,这是一款带有图形用户界面的软件,能够从WGS中识别已知的AR基因,并且具有轻松检测已知AR基因新变体(包括截短蛋白变体)的独特能力。当前的软件解决方案在基因被截短因而可能无功能时不会通知用户,这使得表型预测的准确性降低。SSTAR用户可以将任何感兴趣的AR数据库用作参考比较器,并且可以手动添加影响耐药性的基因,即使这些基因本身不是耐药决定因素(例如孔蛋白和外排泵)。