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Achromobacter xylosoxidans Cellular Pathology Is Correlated with Activation of a Type III Secretion System. Infect Immun 2020 06 22;88(7)

Date

05/06/2020

Pubmed ID

32366575

Pubmed Central ID

PMC7309624

DOI

10.1128/IAI.00136-20

Scopus ID

2-s2.0-85088536617

Abstract

Achromobacter xylosoxidans is increasingly recognized as a colonizer of cystic fibrosis (CF) patients, but the role that A. xylosoxidans plays in pathology remains unknown. This knowledge gap is largely due to the lack of model systems available to study the toxic potential of this bacterium. Recently, a phospholipase A2 (PLA2) encoded by a majority of A. xylosoxidans genomes, termed AxoU, was identified. Here, we show that AxoU is a type III secretion system (T3SS) substrate that induces cytotoxicity to mammalian cells. A tissue culture model was developed showing that a subset of A. xylosoxidans isolates from CF patients induce cytotoxicity in macrophages, suggestive of a pathogenic or inflammatory role in the CF lung. In a toxic strain, cytotoxicity is correlated with transcriptional activation of axoU and T3SS genes, demonstrating that this model can be used as a tool to identify and track expression of virulence determinants produced by this poorly understood bacterium.

Author List

Pickrum AM, DeLeon O, Dirck A, Tessmer MH, Riegert MO, Biller JA, Ledeboer NA, Kirby JR, Frank DW

Authors

John Kirby PhD Chair, Center Associate Director, Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Nathan A. Ledeboer PhD Vice Chair, Professor in the Pathology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Achromobacter denitrificans
Animals
Bacterial Proteins
Biomarkers
Cell Line, Tumor
Cystic Fibrosis
Cytokines
Cytotoxicity, Immunologic
Gram-Negative Bacterial Infections
Host-Pathogen Interactions
Humans
Inflammation Mediators
Mice
Phagocytosis
Type III Secretion Systems
Virulence Factors