title: Variation of Burkholderia cenocepacia virulence potential during cystic fibrosis chronic lung infection.
abstract: During long-term lung infection in cystic fibrosis (CF) patients, Burkholderia cenocepacia faces multiple selective pressures in this highly stressful and fluctuating environment. As a consequence, the initial infecting strain undergoes genetic changes that result in the diversification of genotypes and phenotypes. Whether this clonal expansion influences the pathogenic potential is unclear. The virulence potential of 39 sequential B. cenocepacia (recA lineage IIIA) isolates, corresponding to 3 different clones retrieved from 3 chronically infected CF patients was compared in this study using the non-mammalian infection hosts Galleria mellonella and Caenorhabditis elegans. The isolates used in this retrospective study were picked randomly from selective agar plates as part of a CF Center routine, from the onset of infection until patients' death after 3.5 and 7.5 y or the more recent isolation date after 12.5 y of chronic infection. The infection models proved useful to assess virulence potential diversification, but for some isolates the relative values diverged in C. elegans and G. mellonella. Results also reinforce the concept of the occurrence of clonal diversification and co-existence of multiple phenotypes within the CF lungs, also with respect to pathogenicity. No clear trend of decrease (or increase) of the virulence potential throughout long-term infection was found but there is an apparent tendency for a clone/patient-dependent decrease of virulence when the G. mellonella model was used. The sole avirulent variant in both infection hosts was found to lack the small third replicon previously associated to virulence. Although possible, the in vivo loss of this nonessential megaplasmid was found to be a rare event (1 among a total of 64 isolates examined).
authors.affiliation: a iBB-Institute for Bioengineering and Biosciences , Department of Bioengineering , Instituto Superior Técnico, Universidade de Lisboa , Lisbon , Portugal.
authors.forename: Ana S
authors.initials: AS
authors.lastname: Moreira
authors.affiliation: a iBB-Institute for Bioengineering and Biosciences , Department of Bioengineering , Instituto Superior Técnico, Universidade de Lisboa , Lisbon , Portugal.
authors.forename: Dalila
authors.identifier: 0000-0002-9727-3579
authors.initials: D
authors.lastname: Mil-Homens
authors.affiliation: a iBB-Institute for Bioengineering and Biosciences , Department of Bioengineering , Instituto Superior Técnico, Universidade de Lisboa , Lisbon , Portugal.
authors.forename: Sílvia A
authors.identifier: 0000-0001-9291-9169
authors.initials: SA
authors.lastname: Sousa
authors.affiliation: a iBB-Institute for Bioengineering and Biosciences , Department of Bioengineering , Instituto Superior Técnico, Universidade de Lisboa , Lisbon , Portugal.
authors.forename: Carla P
authors.initials: CP
authors.lastname: Coutinho
authors.affiliation: a iBB-Institute for Bioengineering and Biosciences , Department of Bioengineering , Instituto Superior Técnico, Universidade de Lisboa , Lisbon , Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Pinto-de-Oliveira
authors.affiliation: a iBB-Institute for Bioengineering and Biosciences , Department of Bioengineering , Instituto Superior Técnico, Universidade de Lisboa , Lisbon , Portugal.
authors.forename: Christian G
authors.initials: CG
authors.lastname: Ramos
authors.affiliation: a iBB-Institute for Bioengineering and Biosciences , Department of Bioengineering , Instituto Superior Técnico, Universidade de Lisboa , Lisbon , Portugal.
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Dos Santos
authors.affiliation: a iBB-Institute for Bioengineering and Biosciences , Department of Bioengineering , Instituto Superior Técnico, Universidade de Lisboa , Lisbon , Portugal.
authors.forename: Arsénio M
authors.identifier: 0000-0002-8066-5787
authors.initials: AM
authors.lastname: Fialho
authors.affiliation: a iBB-Institute for Bioengineering and Biosciences , Department of Bioengineering , Instituto Superior Técnico, Universidade de Lisboa , Lisbon , Portugal.
authors.forename: Jorge H
authors.identifier: 0000-0001-8850-274X
authors.initials: JH
authors.lastname: Leitão
authors.affiliation: a iBB-Institute for Bioengineering and Biosciences , Department of Bioengineering , Instituto Superior Técnico, Universidade de Lisboa , Lisbon , Portugal.
authors.forename: Isabel
authors.identifier: 0000-0003-2208-5183
authors.initials: I
authors.lastname: Sá-Correia
mesh_terms: D000818:Animals; D019121:Burkholderia Infections / Q000150:complications / Q000382:microbiology*; D057508:Burkholderia cenocepacia / Q000235:genetics / Q000472:pathogenicity*; D017173:Caenorhabditis elegans / Q000382:microbiology; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000150:complications / Q000382:microbiology*; D004195:Disease Models, Animal; D005838:Genotype; D006801:Humans; D008168:Lung / Q000382:microbiology*; D009036:Moths / Q000382:microbiology; D010641:Phenotype; D012141:Respiratory Tract Infections / Q000150:complications / Q000382:microbiology; D012189:Retrospective Studies; D014774:Virulence
keywords: Burkholderia cenocepacia; Caenorhabditis elegans; Galleria mellonella; cystic fibrosis chronic infection; phenotypic diversification; virulence potential