Intestinal carbapenem-resistant Klebsiella pneumoniae undergoes complex transcriptional reprogramming following immune activation Journal Article
| Authors: | David, C.; Czauderna, A.; Cheng, L.; Lagune, M.; Jung, H. J.; Kim, S. G.; Pamer, E. G.; Prados, J.; Chen, L.; Becattini, S. |
| Article Title: | Intestinal carbapenem-resistant Klebsiella pneumoniae undergoes complex transcriptional reprogramming following immune activation |
| Abstract: | 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. © 2024 The Author(s). Published with license by Taylor & Francis Group, LLC. |
| Keywords: | unclassified drug; genetics; nonhuman; c reactive protein; animal cell; mouse; animal; metabolism; animals; mice; animal experiment; animal model; drug effect; transcriptomics; mice, inbred c57bl; c57bl mouse; gene expression regulation; immunology; antiinfective agent; bacterial protein; anti-bacterial agents; bacterial proteins; reactive oxygen metabolite; electroporation; real time polymerase chain reaction; hydrogen peroxide; immunostimulation; immunity; microbiology; antibiotic sensitivity; intestine; intestines; rna extraction; gene expression regulation, bacterial; neomycin; macrophage activation; klebsiella pneumoniae; gut; cd3 antibody; carbapenem derivative; dextran sulfate; growth curve; humans; human; female; article; rna sequencing; klebsiella infection; carbapenem-resistant enterobacteriaceae; klebsiella infections; carbenicillin; carbapenems; carbapenem resistant klebsiella pneumoniae; carbapenem-resistant klebsiella pneumoniae; camp receptor protein; duf1471 gene |
| Journal Title: | Gut Microbes |
| Volume: | 16 |
| Issue: | 1 |
| ISSN: | 1949-0976 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 2024-01-01 |
| Start Page: | 2340486 |
| Language: | English |
| DOI: | 10.1080/19490976.2024.2340486 |
| PUBMED: | 38659243 |
| PROVIDER: | scopus |
| PMCID: | PMC11057644 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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