Dataset Information

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 bla_KPC-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.

SUBMITTER: Liu Y

PROVIDER: S-EPMC9723571 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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

Liu Ying Y Zhu Shichao S Wei Li L Feng Yu Y Cai Lin L Dunn Steven S McNally Alan A Zong Zhiyong Z

ISME communications 20220822 1

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. M ...[more]

PMID: 37938732

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Project description:Carbapenem-resistantKlebsiella pneumoniae(CR-Kp) is significant threat to public health worldwide. The primary reservoir for CR-Kp is the intestinal tract, where the bacterium is usually present at low density, but can bloom following antibiotic treatment, mostly in hospital settings. The impact of disturbances in the intestinal environment on the fitness, survival, expansion, and drug susceptibility of this pathogen is not well-understood. Nevertheless, gaining such knowledge could lead to innovative intervention strategies for addressing colonization and infection. Here, we adopted anin vivomodel to examine the transcriptional adaptation of a CR-Kp clinical isolate to immune activation in the intestine. We report that as early as 6 hours following host treatment with anti-CD3 antibody, CR-Kp underwent rapid transcriptional changes including downregulation of genes involved in sugar utilization and amino acid biosynthesis, and upregulation of genes involved in amino acid uptake and catabolism, antibiotic resistance, and stress response. In agreement with these findings, the concentration of oxidative species and amino acids was increased in the mouse intestine following treatment. Genes encoding for proteins containing the domain of unknown function (DUF) 1471 were particularly upregulated, however their deletion did not impair CR-Kp fitness in vivoupon immune activation. Transcription factor enrichment analysis identified the global regulator cAMP-Receptor Protein CRP as a potential orchestrator of the observed transcriptional signature. In keeping with the recognized role of CRP in regulating utilization of alternative carbon sources, CRP deletion in CR-Kp resulted in strongly impaired gut colonization, but this effect was not amplified by immune activation. Thus, following intestinal colonization, which occurs in a CRP-dependent manner, CR-Kp can rapidly respond to immune cues by implementing a well-defined and complex transcriptional program whose direct relevance towards bacterial fitness remains cryptic. Further analyses utilizing this model may identify key factors to tackle the intestinal stage of CR-Kp colonization.

Dataset Information

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

Publications

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

Similar Datasets

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