{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T11:19:28Z","timestamp":1788175168061,"version":"build-2803163510"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Sepsis is a life-threatening syndrome characterized by profound immune dysregulation and substantial biological heterogeneity. Here, we conducted a pilot study to explore host immune remodeling in\n                      <jats:italic>Klebsiella<\/jats:italic>\n                      -associated sepsis by combining single-cell RNA sequencing of peripheral blood mononuclear cells with whole-genome sequencing of the corresponding bloodstream isolates.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this prospective observational pilot study, we analyzed peripheral blood mononuclear cells (PBMCs) from two patients with\n                      <jats:italic>Klebsiella<\/jats:italic>\n                      -associated sepsis and two healthy controls (HC) using single-cell RNA sequencing. PBMC composition, differential transcriptional responses, and pathway analysis were assessed across immune subsets. The corresponding bloodstream isolates were characterized by phenotypic antimicrobial susceptibility testing and whole-genome sequencing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared to HC, septic patients showed expansion of the myeloid compartment and contraction of the NK\/T compartment. High-resolution analysis suggested shifts within lymphoid populations. At the transcriptional level, sepsis was associated with compartment-specific enrichment of interferon-related and host-defence pathways, as well as oxidative phosphorylation, ATP synthesis, and mitochondrial electron transport signatures across multiple PBMC subsets. Classical monocytes exhibited a coordinated decrease in MHC class II-related transcripts. The sepsis-associated isolates were identified as\n                      <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                      and\n                      <jats:italic>Klebsiella variicola<\/jats:italic>\n                      and were notable for overall antimicrobial susceptibility, limited resistomes, and absence of canonical hypervirulence determinants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our data provide a preliminary description of immune remodeling during\n                      <jats:italic>Klebsiella<\/jats:italic>\n                      -associated sepsis and suggest that severe clinical disease may be associated with isolates lacking classical multidrug-resistance or hypervirulence features. These findings should be interpreted as preliminary and hypothesis-generating and require validation in larger cohorts with detailed clinical severity assessment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1911804","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:55:04Z","timestamp":1786514104000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Parallel single-cell host immune profiling and pathogen genomic characterization in Klebsiella-associated sepsis: a pilot study"],"prefix":"10.3389","volume":"16","author":[{"given":"Claudia","family":"Rotondo","sequence":"first","affiliation":[{"name":"Microbiology and Biobank Unit, National Institute for Infectious Diseases \u201cLazzaro Spallanzani\u201d, IRCCS","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Rossi","sequence":"additional","affiliation":[{"name":"Microbiology and Biobank Unit, National Institute for Infectious Diseases \u201cLazzaro Spallanzani\u201d, IRCCS","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Properzi","sequence":"additional","affiliation":[{"name":"Microbiology and Biobank Unit, National Institute for Infectious Diseases \u201cLazzaro Spallanzani\u201d, IRCCS","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Chillemi","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Unit in Infectious Diseases, National Institute for Infectious Diseases \u201cLazzaro Spallanzani\u201d, IRCCS","place":["Rome, Italy"]},{"name":"Department of Experimental Medicine, University of Rome \u201cTor Vergata\u201d","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Pietrucci","sequence":"additional","affiliation":[{"name":"Department for Innovation in Biological, Agro-Food and Forest Systems (DIBAF), University of Tuscia","place":["Viterbo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovica","family":"Picarone","sequence":"additional","affiliation":[{"name":"Department for Innovation in Biological, Agro-Food and Forest Systems (DIBAF), University of Tuscia","place":["Viterbo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucrezia","family":"Pierfederici","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Unit in Infectious Diseases, National Institute for Infectious Diseases \u201cLazzaro Spallanzani\u201d, IRCCS","place":["Rome, Italy"]},{"name":"Department of Experimental Medicine, University of Rome \u201cTor Vergata\u201d","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Capecchi","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, National Institute for Infectious Diseases \u201cLazzaro Spallanzani\u201d, IRCCS","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germana","family":"Grassi","sequence":"additional","affiliation":[{"name":"Cellular Immunology and Pharmacology Laboratory, National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Loiacono","sequence":"additional","affiliation":[{"name":"Clinical and Research Infectious Disease Department, National Institute for Infectious Diseases \u201cLazzaro Spallanzani\u201d, IRCCS","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Cimini","sequence":"additional","affiliation":[{"name":"Cellular Immunology and Pharmacology Laboratory, National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Nanni","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore","place":["Rome, Italy"]},{"name":"Fondazione \u201cPoliclinico Universitario A. 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