Arm race among closely-related carbapenem-resistant Klebsiella pneumoniae clones

Abstract

Multiple carbapenem-resistant Klebsiella pneumoniae (CRKP) clones typically co-exist in hospital wards, but often certain clones will dominate. The factors driving this dominance are largely unclear. This study began from a genomic epidemiology analysis and followed by multiple approaches to identify the potential mechanisms driving the successful spread of a dominant clone. 638 patients in a 50-bed ICU were screened. 171 (26.8%) and 21 had CRKP from swabs and clinical specimens, respectively. Many (39.8% of those with ≥7-day ICU stay) acquired CRKP. After removing 18 unable to recover, 174 CRKP isolates were genome sequenced and belonged to six sequence types, with ST11 being the most prevalent (n = 154, 88.5%) and most (n = 169, 97.1%) carrying blaKPC-2. The 154 ST11 isolates belonged to 7 clones, with one (clone 1, KL64 capsular type) being dominant (n = 130, 84.4%). Clone 1 and the second-most common clone (clone 2, KL64, n = 15, 9.7%) emerged simultaneously, which was also detected by genome-based dating. Clone 1 exhibited decreased biofilm formation, shorter environment survival, and attenuated virulence. In murine gut, clone 1 outcompeted clone 2. Transcriptomic analysis showed significant upregulation of the ethanolamine operon in clone 1 when competing with clone 2. Clone 1 exhibited increased utilization of ethanolamine as a nitrogen source. This highlights that reduced virulence and enhanced ability to utilize ethanolamine may promote the success of nosocomial multidrug-resistant clones.