Savin Cyril, Lê-Bury Pierre, Guglielmini Julien, Douché Thibaut, Mas Fiol Guillem, Buzelé Rodolphe, Le Brun Cécile, Bastides Frédéric, François Maud, Birmelé Béatrice, Guichard Laura, Madej Julien, Beau Rémi, Cabanel Nicolas, Dortet Laurent, Matondo Mariette, Dussurget Olivier, Carniel Elisabeth, Lanotte Philippe, Pizarro-Cerdá Javier
Institut Pasteur, Université Paris Cité, Yersinia Research Unit, Paris, France.
Institut Pasteur, Université Paris Cité, Yersinia National Reference Laboratory, Paris, France.
Nat Commun. 2025 Jul 1;16(1):5637. doi: 10.1038/s41467-025-60782-6.
Bacteria exhibit remarkable adaptability in response to selective pressures encountered during infection and antibiotic treatment. We characterize four Yersinia enterocolitica clonal isolates from successive bacteremia episodes that evolved within an elderly patient over 14 years. Their common evolution is characterized by a genome size reduction resulting in the loss of about a hundred genes and a so far undescribed deletion in the DNA gyrase gene gyrA conferring quinolone resistance. Third-generation cephalosporin resistance of the last isolate correlates with a truncation of OmpF in synergy with an increased production of BlaA and AmpC β-lactamases. A strong proteome remodeling of the isolates reveals a perturbed stringent response, as well as impaired metabolism which substantiate their severe growth defects in vitro, accounting for antibiotics tolerance and possibly therapeutic failure. This study documents previously unreported genetic and phenotypic changes associated with in-host adaptation of a pathogenic Yersinia species under antibiotic pressure.
细菌在应对感染和抗生素治疗过程中遇到的选择性压力时表现出显著的适应性。我们对来自一名老年患者14年间连续菌血症发作的4株小肠结肠炎耶尔森菌克隆分离株进行了表征。它们的共同进化特征是基因组大小减小，导致约100个基因丢失，以及在DNA促旋酶基因gyrA中出现了迄今未描述的缺失，从而赋予喹诺酮抗性。最后一株分离株对第三代头孢菌素的抗性与OmpF截短以及BlaA和AmpCβ-内酰胺酶产量增加协同作用有关。分离株强烈的蛋白质组重塑揭示了严格反应受到干扰以及代谢受损，这证实了它们在体外严重的生长缺陷，解释了抗生素耐受性以及可能的治疗失败。本研究记录了在抗生素压力下，致病性耶尔森菌在宿主体内适应过程中以前未报道的遗传和表型变化。
