Vautrin Nicolas, Dahyot Sandrine, Leoz Marie, Caron François, Grand Maxime, Feldmann Audrey, Gravey François, Legris Stéphanie, Ribet David, Alexandre Kévin, Pestel-Caron Martine
Univ Rouen Normandie, Université de Caen Normandie, INSERM, Normandie Univ, DYNAMICURE UMR 1311, F-76000 Rouen, France.
Univ Rouen Normandie, Université de Caen Normandie, INSERM, Normandie Univ, DYNAMICURE UMR 1311, CHU Rouen, department of microbiology, F-76000 Rouen, France.
bioRxiv. 2023 Nov 9:2023.11.08.566351. doi: 10.1101/2023.11.08.566351.
Specific determinants associated with Uropathogenic (UPEC) causing recurrent cystitis are still poorly characterized. The aims of this study were (i) to describe genomic and phenotypic traits associated with recurrence using a large collection of recurrent and paired sporadic UPEC isolates, and (ii) to explore within-host genomic adaptation associated with recurrence using series of 2 to 5 sequential UPEC isolates. Whole genome comparative analyses between 24 recurrent cystitis isolates (RCIs) and 24 phylogenetically paired sporadic cystitis isolates (SCIs) suggested a lower prevalence of putative mobile genetic elements (MGE) in RCIs, such as plasmids and prophages. The intra-patient evolution of the 24 RCI series over time was characterized by SNP occurrence in genes involved in metabolism or membrane transport, and by plasmid loss in 5 out of the 24 RCI series. Genomic evolution occurred early in the course of recurrence, suggesting rapid adaptation to strong selection pressure in the urinary tract. However, RCIs did not exhibit specific virulence factor determinants and could not be distinguished from SCIs by their fitness, biofilm formation, or ability to invade HTB-9 bladder epithelial cells. Taken together, these results suggest a rapid but not convergent adaptation of RCIs that involves both strain- and host-specific characteristics.
与引起复发性膀胱炎的尿路致病性大肠杆菌(UPEC)相关的特定决定因素仍未得到充分表征。本研究的目的是:(i)使用大量复发性和配对散发性UPEC分离株来描述与复发相关的基因组和表型特征;(ii)使用2至5个连续的UPEC分离株系列来探索与复发相关的宿主内基因组适应性。对24株复发性膀胱炎分离株(RCI)和24株系统发育配对的散发性膀胱炎分离株(SCI)进行全基因组比较分析,结果表明RCI中假定的可移动遗传元件(MGE)(如质粒和原噬菌体)的发生率较低。24个RCI系列在患者体内随时间的进化特征是参与代谢或膜转运的基因中出现单核苷酸多态性(SNP),以及24个RCI系列中有5个出现质粒丢失。基因组进化在复发过程早期就已发生,这表明在尿路中能快速适应强大的选择压力。然而,RCI并未表现出特定的毒力因子决定因素,并且在适应性、生物膜形成或侵袭HTB - 9膀胱上皮细胞的能力方面无法与SCI区分开来。综上所述,这些结果表明RCI的适应迅速但不趋同,涉及菌株特异性和宿主特异性特征。