Acquired resistance to innate immune clearance promotes <i>Klebsiella pneumoniae</i> ST258 pulmonary infection.

Abstract

Adaptive changes in the genome of a locally predominant clinical isolate of the multidrug-resistant <i>Klebsiella pneumoniae</i> ST258 (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 Ly6C^hi monocytic myeloid-derived suppressor cells that lacked phagocytic capabilities, expressed IL-10, arginase, and antiinflammatory surface markers. In comparison with other <i>K</i>. <i>pneumoniae</i> strains, 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 ST258 <i>K</i>. <i>pneumoniae</i> isolate 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.