ABSTRACT

Acinetobacter baumannii has become a major healthcare threat that causes nosocomial infections, especially in critically ill patients. The spread of carbapenem-resistant A. baumannii (CRAB) strains has long been a clinical concern. It is important to study the epidemiology and virulence characteristics of different CRAB isolates in order to tailor infection prevention and antibiotic prescribing. In this study, a total of 71 CRAB isolates were collected in the hospital, and clinical characteristics of infections were analyzed. The genomic characteristics and phylogenetic relationships were elucidated based on genome sequencing and analysis. The isolates were assigned to three sequence types (STs, Pasteur) and nine capsular polysaccharide (KL) types, among which ST2/KL22 was the most prevalent CRAB in the hospital. Even though all the ST2/KL22 isolates contained the same reported virulence genes, one specific clade of ST2/KL22 showed more pathogenic in mouse infection model. Complete genomic analysis revealed differences at the oprD locus between the low- and high-virulent isolates. More specifically, a premature stop codon in the low-virulence strains resulted in truncated OprD expression. By evaluating pathogenicity in C57BL/6 J mice, knock-out of oprD in high-virulent isolate resulted in virulence attenuation, and complementing the avirulent strain with full-length oprD from high-virulent isolate enhanced virulence of the former. The oprD gene may be associated with the enhanced virulence of the specific ST2/KL22 clone, which provides a potential molecular marker for screening the hypervirulent A. baumannii strains.

摘要

鲍曼不动杆菌已成为导致医院感染的主要医疗威胁，尤其是在危重患者中。耐碳青霉烯鲍曼不动杆菌的传播(CRAB) 菌株长期以来一直是临床关注的问题。重要的是研究不同 CRAB 分离株的流行病学和毒力特征，以便制定感染预防和抗生素处方。本研究共收集医院内 71 株 CRAB 分离株，分析感染的临床特征。基于基因组测序和分析阐明了基因组特征和系统发育关系。分离株被分为三种序列类型（STs、巴斯德）和九种荚膜多糖（KL）类型，其中 ST2/KL22 是医院中最普遍的 CRAB。尽管所有 ST2/KL22 分离株都含有相同的报告毒力基因，但 ST2/KL22 的一个特定进化枝在小鼠感染模型中表现出更高的致病性。完整的基因组分析揭示了低毒力和高毒力分离株之间的oprD基因座。更具体地说，低毒力菌株中的过早终止密码子导致截短的 OprD 表达。通过评估 C57BL/6 J 小鼠的致病性，敲除高毒力分离株中的oprD导致毒力减弱，用来自高毒力分离株的全长oprD补充无毒株增强了前者的毒力。所述OPRD基因可以与特定ST2 / KL22克隆，它提供了一个潜在的分子标记物用于筛选超毒力的毒力增强相关联鲍曼不动杆菌菌株。