Biomedicine Discovery Institute, Infection & Immunity Program and Department of Microbiology, Monash University, Melbourne, VIC, 3800, Australia.
Department of Pharmacology and Therapeutics, University of Melbourne, Melbourne, VIC, 3010, Australia.
Int J Med Microbiol. 2020 Apr;310(3):151412. doi: 10.1016/j.ijmm.2020.151412. Epub 2020 Feb 5.
Multidrug-resistant (MDR) Acinetobacter baumannii is a critical threat to global health. The type strain ATCC 19606 has been widely used in studying the virulence, pathogenesis and mechanisms of antimicrobial resistance in A. baumannii. However, the lack of a complete genome sequence is a hindrance towards detailed bioinformatic studies. Here we report the generation of a complete genome for ATCC 19606 using PacBio sequencing. ATCC 19606 genome consists of a 3,980,848-bp chromosome and a 9,450-bp plasmid pMAC, and harbours a chromosomal dihydropteroate synthase gene sul2 conferring resistance to sulphonamides and a plasmid-borne ohr gene conferring resistance to peroxides. The genome also contains 69 virulence genes involved in surface adherence, biofilm formation, extracellular phospholipase, iron uptake, immune evasion and quorum sensing. Insertion sequences ISCR2 and ISAba11 are embedded in a 36.1-Kb genomic island, suggesting an IS-mediated large-scale DNA recombination. Furthermore, a genome-scale metabolic model (GSMM) iATCC19606v2 was constructed using the complete genome annotation. The model iATCC19606v2 incorporated a periplasmic compartment, 1,422 metabolites, 2,114 reactions and 1,009 genes, and a set of protein crowding constraints taking into account enzyme abundance limitation. The prediction of bacterial growth on 190 carbon and 95 nitrogen sources achieved a high accuracy of 85.6% compared to Biolog experiment results. Based upon two transposon mutant libraries of AB5075 and ATCC 17978, the predictions of essential genes reached the accuracy of 87.6% and 82.1%, respectively. Together, the complete genome sequence and high-quality GSMM iATCC19606v2 provide valuable tools for antimicrobial systems pharmacological investigations on A. baumannii.
多药耐药（MDR）鲍曼不动杆菌是对全球健康的重大威胁。标准株 ATCC 19606 已被广泛用于研究鲍曼不动杆菌的毒力、发病机制和抗微生物耐药机制。然而，缺乏完整的基因组序列是对详细的生物信息学研究的阻碍。在这里，我们使用 PacBio 测序生成了 ATCC 19606 的完整基因组。ATCC 19606 基因组由 3980848bp 染色体和 9450bp 质粒 pMAC 组成，含有编码对磺胺类药物耐药的染色体二氢喋呤合成酶基因 sul2 和编码对过氧化物耐药的质粒 oh 基因。基因组还包含 69 个与表面黏附、生物膜形成、细胞外磷脂酶、铁摄取、免疫逃避和群体感应相关的毒力基因。插入序列 ISCR2 和 ISAba11 嵌入在一个 36.1-Kb 基因组岛中，表明存在 IS 介导的大规模 DNA 重组。此外，使用完整的基因组注释构建了一个全基因组代谢模型（GSMM）iATCC19606v2。模型 iATCC19606v2 纳入了一个周质腔室、1422 种代谢物、2114 种反应和 1009 种基因，以及一组考虑酶丰度限制的蛋白质拥挤约束。与 Biolog 实验结果相比，190 种碳源和 95 种氮源的细菌生长预测的准确性高达 85.6%。基于 AB5075 和 ATCC 17978 的两个转座子突变体文库，必需基因的预测准确率分别达到 87.6%和 82.1%。总的来说，完整的基因组序列和高质量的 GSMM iATCC19606v2 为鲍曼不动杆菌的抗菌系统药理学研究提供了有价值的工具。
