title: Acquired resistance to innate immune clearance promotesKlebsiella pneumoniaeST258 pulmonary infection.
abstract: Adaptive changes in the genome of a locally predominant clinical isolate of the multidrug-resistantKlebsiella pneumoniaeST258 (KP35) were identified and help to explain the selection of this strain as a successful pulmonary pathogen. The acquisition of 4 new ortholog groups, including an arginine transporter, enabled KP35 to outcompete related ST258 strains lacking these genes. KP35 infection elicited a monocytic response, dominated by Ly6Chimonocytic myeloid-derived suppressor cells that lacked phagocytic capabilities, expressed IL-10, arginase, and antiinflammatory surface markers. In comparison with otherK.pneumoniaestrains, KP35 induced global changes in the phagocytic response identified with proteomics, including evasion of Ca2+and calpain activation necessary for phagocytic killing, confirmed in functional studies with neutrophils. This comprehensive analysis of an ST258K.pneumoniaeisolate reveals ongoing genetic adaptation to host microenvironments and innate immune clearance mechanisms that complements its repertoire of antimicrobial resistance genes and facilitates persistence in the lung.
authors: Department of Pediatrics, Columbia University Medical Center, New York, New York, USA.
authors: Danielle
authors: D
authors: Ahn
authors: Millennium Institute on Immunology and Immunotherapy, Santiago, Chile.|Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Hernán
authors: H
authors: Peñaloza
authors: Department of Medicine, Columbia University Medical Center, New York, New York, USA.
authors: Zheng
authors: Z
authors: Wang
authors: Department of Pediatrics, Columbia University Medical Center, New York, New York, USA.
authors: Matthew
authors: M
authors: Wickersham
authors: Department of Pediatrics, Columbia University Medical Center, New York, New York, USA.
authors: Dane
authors: D
authors: Parker
authors: Proteomics Shared Resource at the Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York, USA.
authors: Purvi
authors: P
authors: Patel
authors: Proteomics Shared Resource at the Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York, USA.
authors: Antonius
authors: A
authors: Koller
authors: Proteomics Shared Resource at the Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York, USA.|Department of Pharmacology, Columbia University Medical Center, New York, New York, USA.
authors: Emily I
authors: EI
authors: Chen
authors: Millennium Institute on Immunology and Immunotherapy, Santiago, Chile.|Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Susan M
authors: SM
authors: Bueno
authors: Department of Medicine, Columbia University Medical Center, New York, New York, USA.
authors: Anne-Catrin
authors: AC
authors: Uhlemann
authors: Department of Pediatrics, Columbia University Medical Center, New York, New York, USA.|Department of Pharmacology, Columbia University Medical Center, New York, New York, USA.
authors: Alice
authors: A
authors: Prince
mesh_terms: D026905:Amino Acid Transport Systems / Q000235:genetics; D000818:Animals; D017920:Antiporters / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D016207:Cytokines / Q000276:immunology; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D007113:Immunity, Innate; D007710:Klebsiella Infections / Q000276:immunology*; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis; D018410:Pneumonia, Bacterial / Q000276:immunology*
chemical_list: D026905:Amino Acid Transport Systems; D017920:Antiporters; C063930:ArcD protein, Bacteria; D001426:Bacterial Proteins; D016207:Cytokines