Within-host microevolution of Pseudomonas aeruginosa in Italian cystic fibrosis patients.
BACKGROUND
Chronic infection with Pseudomonas aeruginosa is a major cause of morbidity and mortality in cystic fibrosis (CF) patients, and a more complete understanding of P. aeruginosa within-host genomic evolution, transmission, and population genomics may provide a basis for improving intervention strategies. Here, we report the first genomic analysis of P. aeruginosa isolates sampled from Italian CF patients.


RESULTS
By genome sequencing of 26 isolates sampled over 19 years from four patients, we elucidated the within-host evolution of clonal lineages in each individual patient. Many of the identified mutations were located in pathoadaptive genes previously associated with host adaptation, and we correlated mutations with changes in CF-relevant phenotypes such as antibiotic resistance. In addition, the genomic analysis revealed that three patients shared the same clone. Furthermore, we compared the genomes of the Italian CF isolates to a panel of genome sequenced strains of P. aeruginosa from other countries. Isolates from two of the Italian lineages belonged to clonal complexes of P. aeruginosa that have previously been identified in Danish CF patients, and our genomic comparison showed that clonal isolates from the same country may be more distantly related than clonal isolates from different countries.


CONCLUSIONS
This is the first whole-genome analysis of P. aeruginosa isolated from Italian CF patients, and together with both phenotypic and clinical information this dataset facilitates a more detailed understanding of P. aeruginosa within-host genomic evolution, transmission, and population genomics. We conclude that the evolution of the Italian lineages resembles what has been found in other countries.
Department of Immunology and Microbiology, Costerton Biofilm Center, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. rmarvig@gmail.com.|Center for Genomic Medicine, Rigshospitalet, Copenhagen, Denmark. rmarvig@gmail.com.
Rasmus Lykke
RL
Marvig
Department of Paediatric Medicine, Cystic Fibrosis Centre, Anna Meyer Children's University Hospital, Florence, Italy. daniela.dolce@meyer.it.
Daniela
D
Dolce
Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark. lemad@bio.dtu.dk.|The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark. lemad@bio.dtu.dk.
Lea M
LM
Sommer
Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark. bent@cbs.dtu.dk.
Bent
B
Petersen
Department of Immunology and Microbiology, Costerton Biofilm Center, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. ociofu@sund.ku.dk.
Oana
O
Ciofu
Department of Paediatric Medicine, Cystic Fibrosis Centre, Anna Meyer Children's University Hospital, Florence, Italy. silvia.campana@meyer.it.
Silvia
S
Campana
Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark. sm@bio.dtu.dk.|The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark. sm@bio.dtu.dk.
Søren
S
Molin
Department of Paediatric Medicine, Cystic Fibrosis Centre, Anna Meyer Children's University Hospital, Florence, Italy. giovanni.taccetti@meyer.it.
Giovanni
G
Taccetti
Department of Immunology and Microbiology, Costerton Biofilm Center, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. hkj@biosustain.dtu.dk.|The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark. hkj@biosustain.dtu.dk.
Helle Krogh
HK
Johansen
D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications*; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D016680:Genome, Bacterial; D006801:Humans; D007223:Infant; D007558:Italy; D008297:Male; D008969:Molecular Sequence Data; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D012137:Respiratory System / Q000382:microbiology*; D017422:Sequence Analysis, DNA; D055815:Young Adult
D004269:DNA, Bacterial