Virulence factors are preserved within carbapenem-resistant Acinetobacter baumannii clades

Carbapenem-resistant Acinetobacter baumannii (CRAB) is an important threat to hospitalized patients. The virulence of A. baumannii varies between strains and geographic locations, which is believed to be related to its genetic plasticity. A comprehensive evaluation of virulence factor (VF) content of CRAB across genetically related clones is lacking. Therefore, we aimed to determine the evolution of VFs among 246 CRAB isolates belonging to major STs, ST2 and ST3. We used WGS to assess 136 VFs and found that 110 VFs were present in most isolates (49 VFs were universally present, 61 were ubiquitous) and 25 occurred sporadically. The distribution of the 25 sporadic VF genes was homogenous in ST3 but heterogeneous in ST2. Within ST2, we found high intra-clade homogeneity and high inter-clade heterogeneity of VFs. The homogeneity of VF content in ST2 clades and its uniformity in ST3 suggest a distant evolutionary segregation of VFs at the root of ST/clade divergence. VF content reflects remote events resulting in minimal variation between isolates belonging to the same ST/clade. Thus, the alleged differences in virulence of CRAB strains between geographical locations reflect differences in clonal distribution.耐碳青霉烯类鲍曼不动杆菌（Carbapenem-resistant Acinetobacter baumannii, CRAB）是住院患者面临的重要临床威胁。鲍曼不动杆菌的毒力特性因菌株及地理位置而异，该现象被认为与其遗传可塑性密切相关。目前尚无针对不同遗传相关克隆群中CRAB毒力因子（virulence factor, VF）组成的全面评估研究。因此，本研究旨在明确隶属于两大主要序列型（sequence type, ST）ST2与ST3的246株CRAB分离株的毒力因子演化规律。我们采用全基因组测序（whole genome sequencing, WGS）对136种毒力因子进行检测分析，结果显示110种毒力因子在多数分离株中存在（其中49种为普遍存在，61种为广泛分布），剩余25种仅呈零星分布。这25种零星分布的毒力因子基因在ST3中分布均一，而在ST2中则呈现异质性特征。在ST2群体内，我们发现克隆群内部毒力因子组成具有高度同源性，而不同克隆群之间则存在显著异质性。ST2克隆群内毒力因子组成的均一性，以及ST3中毒力因子分布的一致性，提示毒力因子在序列型/克隆群分化的早期即发生了远距离演化分离。毒力因子组成反映了导致同一序列型/克隆群分离株间差异极小的遥远演化事件。因此，此前报道的不同地理位置间CRAB菌株毒力差异，实则反映了各克隆群在当地的分布差异。