Faculty Collaboration Database

Identification of Virulence Factors Involved in a Murine Model of Severe Achromobacter xylosoxidans Infection. Infect Immun 2023 Jul 18;91(7):e0003723

Date

05/31/2023

Pubmed ID

37255468

Pubmed Central ID

PMC10353400

DOI

10.1128/iai.00037-23

Scopus ID

2-s2.0-85165519693 (requires institutional sign-in at Scopus site)   3 Citations

Abstract

Achromobacter xylosoxidans (Ax) is an opportunistic pathogen and causative agent of numerous infections particularly in immunocompromised individuals with increasing prevalence in cystic fibrosis (CF). To date, investigations have focused on the clinical epidemiology and genomic comparisons of Ax isolates, yet little is known about disease pathology or the role that specific virulence factors play in tissue invasion or damage. Here, we model an acute Ax lung infection in immunocompetent C57BL/6 mice and immunocompromised CF mice, revealing a link between in vitro cytotoxicity and disease in an intact host. Mice were intratracheally challenged with sublethal doses of a cytotoxic (GN050) or invasive (GN008) strain of Ax. Bacterial burden, immune cell populations, and inflammatory markers in bronchoalveolar lavage fluid and lung homogenates were measured at different time points to assess disease severity. CF mice had a similar but delayed immune response toward both Ax strains compared to C57BL/6J mice. GN050 caused more severe disease and higher mortality which correlated with greater bacterial burden and increased proinflammatory responses in both mouse models. In agreement with the cytotoxicity of GN050 toward macrophages in vitro, mice challenged with GN050 had fewer macrophages. Mutants with transposon insertions in predicted virulence factors of GN050 showed that disease severity depended on the type III secretion system, Vi capsule, antisigma-E factor, and partially on the ArtA adhesin. The development of an acute infection model provides an essential tool to better understand the infectivity of diverse Ax isolates and enable improved identification of virulence factors important to bacterial persistence and disease.

Author List

Wills BM, Garai P, Riegert MO, Sanchez FT, Pickrum AM, Frank DW, Brockman KL

Author

Kenneth Brockman PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin

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

Achromobacter denitrificans
Animals
Cystic Fibrosis
Disease Models, Animal
Gram-Negative Bacterial Infections
Mice
Mice, Inbred C57BL
Virulence Factors