SGER: Investigation of Antimicrobial Resistance Genes in the Annotation of Bacillus Anthracis Genomens

疾病控制和预防中心正在通过机构间转移的方式获得资金，用于研究抗生素耐药性和炭疽芽孢杆菌基因组中抗生素基因注释的新项目。炭疽芽孢杆菌是一种对多种抗生素敏感的重要病原体。然而，奇怪的是，它携带了对许多相同抗生素产生耐药性的基因编码。通过实验室实验，本研究将确定炭疽杆菌菌株中被鉴定为青霉素、四环素或大环内酯类耐药基因的哪个位点实际上编码了耐药决定因素；不正确的注释将根据验证的数据进行更正。将分析抗性决定因素的上游和下游的DNA序列，以确定是否存在移动遗传元件。本研究将提高炭疽芽孢杆菌基因组注释的质量和实用性。当生物体暴露于抗菌剂时，还将研究产生耐药表型的可能性。所有对基因组注释的更正将通过提交给公共数据库向科学界开放。有关基因鉴定、表达和相关抗菌药物敏感性表型的数据将发表在适当的同行评审期刊上。该项目将为学生提供细菌遗传学、生物信息学和分子实验室技术方面的培训。生物威胁剂耐药基因的验证信息对国家生物防御具有重要意义。在选择广泛分发和对公众进行大规模治疗的抗微生物剂时，必须确认并考虑到任何潜在的耐药性。在抗菌素耐药基因或相关DNA序列中检测和验证的任何多样性对于鉴定和追踪炭疽芽孢杆菌菌株进行微生物法医鉴定至关重要。

Funds are being provided to the Centers for Disease Control and Prevention via an interagency transfer for a new project on antibiotic resistance and antibiotic gene annotation in the Bacillus anthracis genome. Bacillus anthracis is an important pathogen that is sensitive to many antibiotics. Yet it, curiously, carries genetic coding for resistance to many of these same antibiotics. Through laboratory experiments, this research will determine which of the loci identified as penicillin, tetracycline, or macrolide resistance genes in strains of B. anthracis actually encode a resistance determinant; the incorrect annotations will be corrected based on the verified data. DNA sequences upstream and downstream of the resistance determinants will be analyzed to determine if mobile genetic elements are present. This research will improve the quality and usefulness of B. anthracis genome annotations. The potential for developing a resistant phenotype when the organism is exposed to antimicrobial agents will also be investigated. All corrections to genome annotations will be made available to the scientific community by submission to public databases. Data on gene identification, expression, and associated antimicrobial susceptibility phenotypes will be published in appropriate peer-reviewed journals. This project will be providing student training in bacterial genetics, bioinformatics, and molecular laboratory techniques. Validated information on antimicrobial resistance genes in biothreat agents is of particular importance to national biodefense. Any potential for resistance must be confirmed and taken into consideration when selecting an antimicrobial agent for widespread distribution and for mass treatment of the public. Any diversity detected and verified in the antimicrobial resistance genes or in the associated DNA sequences will be extremely important in identifying and tracking B. anthracis strains for microbial forensics.