FFC#18/2019

Investigating Achromobacter xylosoxidans pathogenicity and clinical role in CF lung infection

FFC#18/2019

Investigating Achromobacter xylosoxidans pathogenicity and clinical role in CF lung infection

PRINCIPAL INVESTIGATOR

Maria M. Lleò (Dip. Diagnostica e Sanità Pubblica, Università di Verona)

RESEARCHERS

10

CATEGORY

AREA 3 Bronchopulmonary infection

DURATION

2 years

GOAL

€ 80.000 €

RESULTS

Achromobacter xylosoxidans is an emergent pathogens in Cystic Fibrosis isolated frequently from the sputum of CF patients. Similarly to the other Gram-negative bacteria, Achromobacter xylosoxidans posses some known virulence factors, such as lipopolisaccaride, but other specific charatteristics of  its pathogenicity are still under study. This bacterial species seems to be able to cause chronic lung infection but is clinical role is not completely clear yet. In this research project we have  evaluated some possible mechanisms of virulence in a large series of clinical CF strains by analyzing their capability of inducing mortality in Galleria mellonella larvae and the ability of syntetizing biofilm and cause citotoxicity in CF bronquial cell cultures. Strains causing occasional infections induced higher mortality percentage in larvae with respect to strains causing lung chronic colonization while these last strains showed higher level of citotoxicity. There were not significant differences as regards the biofilm production. The analyzed strains have been subsequently classified in three groups on the basis of their proved level of virulence and isolates from each group were inoculated endotraqueally in transgenic CF mice. The most virulence strains induced a strong infection and high level of lung inflammation that caused death of all the animals while strains with low level of virulence, in that did not produce biofilm, citotoxicity or larvae mortality, were rapidly eliminated from the mice immunological response without inducing neither inflammation nor dead. The results obtained would contribute to define the clinical role of Achromobacter xylosoxidans in CF  and to provide a series of characteristics that will allow to evaluate the virulence level of the different clinical strains.

Pubblications

  • Lleò Maria del Mar et al, Genomic characterization of Achromobacter species isolates from chronic and occasional lung infection in cystic fibrosis patients, Microbial genomics vol. 7,7 (2021): 000606
  • Lleò Maria del Mar et al, Mobilome Analysis of Achromobacter spp. Isolates from Chronic and Occasional Lung Infection in Cystic Fibrosis Patients, Microorganisms vol. 9,1 130. 8 Jan. 2021

Abstract 

  • Lleò Maria del Mar, Virulence and antibiotic resistance of Achromobacter spp. isolates from chronic and occasional lung infection in cystic fibrosis patients, North American Cystic Fibrosis Conference, November 2 – 5, 2021, Fully Virtual 2021
  • Veschetti L, Hypermutation as an evolutionary mechanism for Achromobacter spp. in cystic fibrosis lung infection, 43rd European Cystic Fibrosis Conference – 2020 (ECFC), virtual conference 2020

OTHER RESULTS

FFC#1/2023

Tezacaftor, one of the components of Kaftrio, induces an accumulation of dihydroceramides both in vitro and in vivo in animal models

FFC#4/2023

Pseudopaline–aztreonam conjugates exhibited enhanced antimicrobial activity against Pseudomonas aeruginosa compared to aztreonam alone

FFC#10/2023

Several drugs already approved for human use inhibit the growth of P. aeruginosa, its virulence, or its ability to form biofilms in vitro