Title | Acquired resistance to innate immune clearance promotes ST258 pulmonary infection. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Ahn D, PeƱaloza H, Wang Z, Wickersham M, Parker D, Patel P, Koller A, Chen EI, Bueno SM, Uhlemann A-C, Prince A |
Journal | JCI Insight |
Volume | 1 |
Issue | 17 |
Pagination | e89704 |
Date Published | 2016 Oct 20 |
ISSN | 2379-3708 |
Keywords | Amino Acid Transport Systems, Animals, Antiporters, Bacterial Proteins, Cytokines, Drug Resistance, Multiple, Bacterial, Humans, Immunity, Innate, Klebsiella Infections, Klebsiella pneumoniae, Male, Mice, Mice, Inbred C57BL, Monocytes, Neutrophils, Phagocytosis, Pneumonia, Bacterial |
Abstract | Adaptive changes in the genome of a locally predominant clinical isolate of the multidrug-resistant 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 monocytic myeloid-derived suppressor cells that lacked phagocytic capabilities, expressed IL-10, arginase, and antiinflammatory surface markers. In comparison with other . strains, KP35 induced global changes in the phagocytic response identified with proteomics, including evasion of Ca and calpain activation necessary for phagocytic killing, confirmed in functional studies with neutrophils. This comprehensive analysis of an ST258 . 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. |
DOI | 10.1172/jci.insight.89704 |
Alternate Journal | JCI Insight |
PubMed ID | 27777978 |
PubMed Central ID | PMC5070956 |
Grant List | S10 RR027050 / RR / NCRR NIH HHS / United States R35 HL135800 / HL / NHLBI NIH HHS / United States R01 HL073989 / HL / NHLBI NIH HHS / United States R01 AI116939 / AI / NIAID NIH HHS / United States P30 CA013696 / CA / NCI NIH HHS / United States K12 HD047349 / HD / NICHD NIH HHS / United States |
Submitted by api_import on December 20, 2019 - 3:16pm