Intestinal carbapenem-resistant Klebsiella pneumoniae undergoes complex transcriptional reprogramming following immune activation

Article Article scientifique Article Intestinal carbapenem-resistant Klebsiella pneumoniae undergoes complex transcriptional reprogramming following immune activation eng 2024-04-24 2024-04-24 author David Clément Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.,Geneva Centre for Inflammation Research, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 949356 Département de pathologie et immunologie (PATIM) author Czauderna Aleksander Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.,Geneva Centre for Inflammation Research, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 949879 Département de pathologie et immunologie (PATIM) author Cheng Liqing Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.,Geneva Centre for Inflammation Research, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 957079 Département de pathologie et immunologie (PATIM) author Lagune Marion Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.,Geneva Centre for Inflammation Research, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 985532 Département de pathologie et immunologie (PATIM) author Jung Hea-Jin Immunology Program, Sloan Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. author Kim Sohn G Immunology Program, Sloan Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. author Pamer Eric G Immunology Program, Sloan Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.,Duchossois Family Institute, University of Chicago, Chicago, IL, USA. author Prados Julien 0000-0002-8546-241X Bioinformatics Support Platform for data analysis, Faculty of medicine, University of Geneva, Geneva, Switzerland. 561771 Services communs de la faculté de médecine (SCMU) author Chen Liang Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, USA. author Becattini Simone 0000-0001-5985-0403 Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.,Geneva Centre for Inflammation Research, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 949421 Département de pathologie et immunologie (PATIM) 2340486 10.1080/19490976.2024.2340486 38659243 1949-0976 PMC11057644 https://www.tandfonline.com/doi/full/10.1080/19490976.2024.2340486 Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is a significant threat to public health worldwide. The primary reservoir for CR-Kp is the intestinal tract. There, 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, yet it may be relevant to devise strategies to tackle CR-Kp colonization and infection. Here, we adopted an in vivo model 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, treatment increased the concentration of oxidative species and amino acids in the mouse intestine. Genes encoding for proteins containing the domain of unknown function (DUF) 1471 were strongly upregulated, however their deletion did not impair CR-Kp fitness in vivo upon 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, although 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 toward bacterial fitness warrants further investigation. Additional analyses utilizing this model may identify key factors to tackle CR-Kp colonization of the intestine. Carbapenem-resistant Klebsiella pneumoniae Gut Immunity Transcriptomics Dewey 616.07 Swiss National Science Foundation Harnessing the interactions between gut microbiota and immune system 187018 CH Careers NCI NIH HHS P30 CA008748 137 Département de pathologie et immunologie 21F false 1340 Host-Microbe Interactions 1027 48a82112-9f30-4dde-a32a-47c02fceac29 Bioinformatics Support Platform 0a6434c9-7972-44ea-8708-82e501660dc7 Biomedical Data Science Facility https://yareta.unige.ch/archives/3b02a7f9-e034-488e-ad04-6d8146101608 Gut microbes 16 1 f568e742-7368-4089-ae5b-29497359c532 Article (Published version) Public Intestinal carbapenem-resistant Kle1.pdf 7550319 application/pdf CC BY-4.0 c45b3e3cc8af49ef75d7a79cdf222a4dba9c51e56a75673837e0a2b403a2292c 800f9400-3b23-4687-a40e-8e2fc39043c5 Supplemental data Public kgmi_a_2340486_sm5421.zip 8847517 application/zip b29435343a8784b7d76081f525e7c171eeb8f91d9d8cd65a34328f346fa1c6d6 openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

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Intestinal carbapenem-resistant Klebsiella pneumoniae undergoes complex transcriptional reprogramming following immune activation	Gut microbes			2024	215	87

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