title: Mucoid morphotype variation of Burkholderia multivorans during chronic cystic fibrosis lung infection is correlated with changes in metabolism, motility, biofilm formation and virulence.
abstract: Burkholderia cepacia complex (Bcc) bacteria are opportunistic pathogens infecting hosts such as cystic fibrosis (CF) patients. Long-term Bcc infection of CF patients' airways has been associated with emergence of phenotypic variation. Here we studied two Burkholderia multivorans clonal isolates displaying different morphotypes from a chronically infected CF patient to evaluate trait development during lung infection. Expression profiling of mucoid D2095 and non-mucoid D2214 isolates revealed decreased expression of genes encoding products related to virulence-associated traits and metabolism in D2214. Furthermore, D2214 showed no exopolysaccharide production, lower motility and chemotaxis, and more biofilm formation, particularly under microaerophilic conditions, than the clonal mucoid isolate D2095. When Galleria mellonella was used as acute infection model, D2214 at a cell number of approximately 7 × 10⁶ c.f.u. caused a higher survival rate than D2095, although 6 days post-infection most of the larvae were dead. Infection with the same number of cells by mucoid D2095 caused larval death by day 4. The decreased expression of genes involved in carbon and nitrogen metabolism may reflect lower metabolic needs of D2214 caused by lack of exopolysaccharide, but also by the attenuation of pathways not required for survival. As a result, D2214 showed higher survival than D2095 in minimal medium for 28 days under aerobic conditions. Overall, adaptation during Bcc chronic lung infections gave rise to genotypic and phenotypic variation among isolates, contributing to their fitness while maintaining their capacity for survival in this opportunistic human niche.
authors.affiliation: IBB - Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, IST, Lisbon, Portugal.
authors.forename: Inês N
authors.initials: IN
authors.lastname: Silva
authors.affiliation: IBB - Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, IST, Lisbon, Portugal.
authors.forename: Ana S
authors.initials: AS
authors.lastname: Ferreira
authors.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, 2780-156 Oeiras, Portugal.
authors.forename: Jörg D
authors.initials: JD
authors.lastname: Becker
authors.affiliation: Division of Infectious and Immunological Diseases, Department of Paediatrics and Centre for Understanding and Preventing Infection in Children, Faculty of Medicine, University of British Columbia, 950 W 28th Ave, Vancouver, BC V5Z 4H4, Canada.
authors.forename: James E A
authors.initials: JEA
authors.lastname: Zlosnik
authors.affiliation: Division of Infectious and Immunological Diseases, Department of Paediatrics and Centre for Understanding and Preventing Infection in Children, Faculty of Medicine, University of British Columbia, 950 W 28th Ave, Vancouver, BC V5Z 4H4, Canada.
authors.forename: David P
authors.initials: DP
authors.lastname: Speert
authors.affiliation: Plant Biology Division, Samuel Roberts Noble Foundation, 2510 Sam Noble Parkway, Ardmore, OK 73401, USA.
authors.forename: Ji
authors.initials: J
authors.lastname: He
authors.affiliation: IBB - Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, IST, Lisbon, Portugal.
authors.forename: Dalila
authors.initials: D
authors.lastname: Mil-Homens
authors.affiliation: Department of Bioengineering, Instituto Superior Técnico (IST), Av. Rovisco Pais, 1049-001 Lisbon, Portugal.|IBB - Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, IST, Lisbon, Portugal.
authors.forename: Leonilde M
authors.initials: LM
authors.lastname: Moreira
mesh_terms: D000222:Adaptation, Physiological; D018441:Biofilms; D019121:Burkholderia Infections / Q000382:microbiology*; D042602:Burkholderia cepacia complex / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000472:pathogenicity*; D003550:Cystic Fibrosis / Q000150:complications*; D004269:DNA, Bacterial / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D005838:Genotype; D006801:Humans; D008168:Lung / Q000382:microbiology; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D009894:Opportunistic Infections / Q000382:microbiology; D010641:Phenotype; D012329:RNA, Bacterial / Q000235:genetics; D012141:Respiratory Tract Infections / Q000382:microbiology*; D059467:Transcriptome; D014774:Virulence
chemical_list: D004269:DNA, Bacterial; D012329:RNA, Bacterial