Department of Biological Sciences, State University of New York at Albany, Albany, NY, USA.
Institute for Infection Prevention and Hospital Epidemiology, Medical Centre, University of Freiburg, Freiburg, Germany.
Nat Commun. 2024 Aug 14;15(1):6969. doi: 10.1038/s41467-024-51374-x.
Bloodstream infections caused by the opportunistic pathogen Klebsiella pneumoniae are associated with adverse health complications and high mortality rates. Antimicrobial resistance (AMR) limits available treatment options, thus exacerbating its public health and clinical burden. Here, we aim to elucidate the population structure of K. pneumoniae in bloodstream infections from a single medical center and the drivers that facilitate the dissemination of AMR. Analysis of 136 short-read genome sequences complemented with 12 long-read sequences shows the population consisting of 94 sequence types (STs) and 99 clonal groups, including globally distributed multidrug resistant and hypervirulent clones. In vitro antimicrobial susceptibility testing and in silico identification of AMR determinants reveal high concordance (90.44-100%) for aminoglycosides, beta-lactams, carbapenems, cephalosporins, quinolones, and sulfonamides. IncF plasmids mediate the clonal (within the same lineage) and horizontal (between lineages) transmission of the extended-spectrum beta-lactamase gene bla. Nearly identical plasmids are recovered from isolates over a span of two years indicating long-term persistence. The genetic determinants for hypervirulence are carried on plasmids exhibiting genomic rearrangement, loss, and/or truncation. Our findings highlight the importance of considering both the genetic background of host strains and the routes of plasmid transmission in understanding the spread of AMR in bloodstream infections.
机会性病原体肺炎克雷伯菌引起的血流感染与不良健康并发症和高死亡率相关。抗生素耐药性（AMR）限制了可用的治疗选择，从而加剧了其公共卫生和临床负担。在这里，我们旨在阐明单个医疗中心血流感染中肺炎克雷伯菌的种群结构以及促进 AMR 传播的驱动因素。对 136 个短读长基因组序列的分析，加上 12 个长读长序列，表明该种群由 94 个序列型（ST）和 99 个克隆群组成，包括全球分布的多药耐药和高毒力克隆。体外抗菌药敏试验和 AMR 决定因素的计算机识别显示，氨基糖苷类、β-内酰胺类、碳青霉烯类、头孢菌素类、喹诺酮类和磺胺类药物的高度一致性（90.44-100%）。IncF 质粒介导了广泛耐药β-内酰胺酶基因 bla 的克隆（同一谱系内）和水平（谱系之间）传播。在两年的时间内，从分离株中回收了几乎相同的质粒，表明其长期存在。高毒力的遗传决定因素存在于表现出基因组重排、缺失和/或截断的质粒上。我们的研究结果强调了在理解血流感染中 AMR 的传播时，既要考虑宿主菌株的遗传背景，又要考虑质粒传播途径的重要性。
