Achromobacter xylosoxidans Cellular Pathology Is Correlated with Activation of a Type III Secretion System. Infect Immun 2020 Jun 22;88(7)
Date
05/06/2020Pubmed ID
32366575Pubmed Central ID
PMC7309624DOI
10.1128/IAI.00136-20Scopus ID
2-s2.0-85088536617 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
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 DWAuthors
John Kirby PhD Chair, Center Associate Director, Professor in the Microbiology and Immunology department at Medical College of WisconsinNathan 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 denitrificansAnimals
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
