Acquired Resistance to Innate Immune Clearance Promotes ST258 Pulmonary Infection

Overview

Journal JCI Insight

Specialties Biomedical Engineering
General Medicine

Date 2016 Oct 26

PMID 27777978

Citations 42

Authors

Danielle Ahn

Hernan Penaloza

Zheng Wang

Matthew Wickersham

Dane Parker

Purvi Patel

Antonius Koller

Emily I Chen

Susan M Bueno

Anne-Catrin Uhlemann

Alice Prince

Affiliations

Soon will be listed here.

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.

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