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Comparative genomics and biological characterization of sequential Pseudomonas aeruginosa isolates from persistent airways infection.

Bianconi I, Jeukens J, Freschi L, Alcalá-Franco B, Facchini M, Boyle B, Molinaro A, Kukavica-Ibrulj I, Tümmler B, Levesque RC, Bragonzi A - BMC Genomics (2015)

Bottom Line: Pathological analysis of murine lungs confirmed advanced chronic pulmonary disease, inflammation and mucus secretory cells hyperplasia.Further, comparative genomic analyses with sequential RP isolates showed signatures of pathoadaptive mutations in virulence factors potentially linked to the development of chronic infections in CF.The genome plasticity of P. aeruginosa particularly in the RP73 strain strongly indicated that these alterations may form the genetic basis defining host-bacteria interactions leading to a persistent lifestyle in human lungs.

View Article: PubMed Central - PubMed

Affiliation: Infections and Cystic Fibrosis Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy. bianconi.irene@hsr.it.

ABSTRACT

Background: Pseudomonas aeruginosa establishes life-long chronic airway infections in cystic fibrosis (CF) patients. As the disease progresses, P. aeruginosa pathoadaptive variants are distinguished from the initially acquired strain. However, the genetic basis and the biology of host-bacteria interactions leading to a persistent lifestyle of P. aeruginosa are not understood. As a model system to study long term and persistent CF infections, the P. aeruginosa RP73, isolated 16.9 years after the onset of airways colonization from a CF patient, was investigated. Comparisons with strains RP1, isolated at the onset of the colonization, and clonal RP45, isolated 7 years before RP73 were carried out to better characterize genomic evolution of P. aeruginosa in the context of CF pathogenicity.

Results: Virulence assessments in disease animal model, genome sequencing and comparative genomics analysis were performed for clinical RP73, RP45, RP1 and prototype strains. In murine model, RP73 showed lower lethality and a remarkable capability of long-term persistence in chronic airways infection when compared to other strains. Pathological analysis of murine lungs confirmed advanced chronic pulmonary disease, inflammation and mucus secretory cells hyperplasia. Genomic analysis predicted twelve genomic islands in the RP73 genome, some of which distinguished RP73 from other prototype strains and corresponded to regions of genome plasticity. Further, comparative genomic analyses with sequential RP isolates showed signatures of pathoadaptive mutations in virulence factors potentially linked to the development of chronic infections in CF.

Conclusions: The genome plasticity of P. aeruginosa particularly in the RP73 strain strongly indicated that these alterations may form the genetic basis defining host-bacteria interactions leading to a persistent lifestyle in human lungs.

No MeSH data available.


Related in: MedlinePlus

Core genome phylogeny for RP isolates and strains representative of P. aeruginosa diversity. The figure represents a partial view of the tree to show the relationships between RP1, RP45 and RP73. The position of RP1 is indicated in blue, while the position of RP45 and RP73 is indicated in red. PA14 is distantly related to all these strains
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Fig5: Core genome phylogeny for RP isolates and strains representative of P. aeruginosa diversity. The figure represents a partial view of the tree to show the relationships between RP1, RP45 and RP73. The position of RP1 is indicated in blue, while the position of RP45 and RP73 is indicated in red. PA14 is distantly related to all these strains

Mentions: In order to study the evolution of chronic infection and determine which genetic determinants are involved in this process, further comparisons were made among RP isolates. First, analyses were carried out to study the relationship between these three strains. A core genome phylogeny was performed using 53 sequences from a previous study [24] representing an extensive sampling of P. aeruginosa’s diversity. In the resulting tree (Fig. 5), RP73 and RP45 cluster together while RP1 is found in a different and independent branch. A multi-locus sequence typing (MLST) analysis was also performed. RP73 and RP45 shared the same MLST profile while RP1 showed a different one (Additional file 4). All these analyses suggest that RP73 and RP45 are close to each other from a genetic point of view, while RP1 is more distantly related.Fig. 5


Comparative genomics and biological characterization of sequential Pseudomonas aeruginosa isolates from persistent airways infection.

Bianconi I, Jeukens J, Freschi L, Alcalá-Franco B, Facchini M, Boyle B, Molinaro A, Kukavica-Ibrulj I, Tümmler B, Levesque RC, Bragonzi A - BMC Genomics (2015)

Core genome phylogeny for RP isolates and strains representative of P. aeruginosa diversity. The figure represents a partial view of the tree to show the relationships between RP1, RP45 and RP73. The position of RP1 is indicated in blue, while the position of RP45 and RP73 is indicated in red. PA14 is distantly related to all these strains
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4696338&req=5

Fig5: Core genome phylogeny for RP isolates and strains representative of P. aeruginosa diversity. The figure represents a partial view of the tree to show the relationships between RP1, RP45 and RP73. The position of RP1 is indicated in blue, while the position of RP45 and RP73 is indicated in red. PA14 is distantly related to all these strains
Mentions: In order to study the evolution of chronic infection and determine which genetic determinants are involved in this process, further comparisons were made among RP isolates. First, analyses were carried out to study the relationship between these three strains. A core genome phylogeny was performed using 53 sequences from a previous study [24] representing an extensive sampling of P. aeruginosa’s diversity. In the resulting tree (Fig. 5), RP73 and RP45 cluster together while RP1 is found in a different and independent branch. A multi-locus sequence typing (MLST) analysis was also performed. RP73 and RP45 shared the same MLST profile while RP1 showed a different one (Additional file 4). All these analyses suggest that RP73 and RP45 are close to each other from a genetic point of view, while RP1 is more distantly related.Fig. 5

Bottom Line: Pathological analysis of murine lungs confirmed advanced chronic pulmonary disease, inflammation and mucus secretory cells hyperplasia.Further, comparative genomic analyses with sequential RP isolates showed signatures of pathoadaptive mutations in virulence factors potentially linked to the development of chronic infections in CF.The genome plasticity of P. aeruginosa particularly in the RP73 strain strongly indicated that these alterations may form the genetic basis defining host-bacteria interactions leading to a persistent lifestyle in human lungs.

View Article: PubMed Central - PubMed

Affiliation: Infections and Cystic Fibrosis Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy. bianconi.irene@hsr.it.

ABSTRACT

Background: Pseudomonas aeruginosa establishes life-long chronic airway infections in cystic fibrosis (CF) patients. As the disease progresses, P. aeruginosa pathoadaptive variants are distinguished from the initially acquired strain. However, the genetic basis and the biology of host-bacteria interactions leading to a persistent lifestyle of P. aeruginosa are not understood. As a model system to study long term and persistent CF infections, the P. aeruginosa RP73, isolated 16.9 years after the onset of airways colonization from a CF patient, was investigated. Comparisons with strains RP1, isolated at the onset of the colonization, and clonal RP45, isolated 7 years before RP73 were carried out to better characterize genomic evolution of P. aeruginosa in the context of CF pathogenicity.

Results: Virulence assessments in disease animal model, genome sequencing and comparative genomics analysis were performed for clinical RP73, RP45, RP1 and prototype strains. In murine model, RP73 showed lower lethality and a remarkable capability of long-term persistence in chronic airways infection when compared to other strains. Pathological analysis of murine lungs confirmed advanced chronic pulmonary disease, inflammation and mucus secretory cells hyperplasia. Genomic analysis predicted twelve genomic islands in the RP73 genome, some of which distinguished RP73 from other prototype strains and corresponded to regions of genome plasticity. Further, comparative genomic analyses with sequential RP isolates showed signatures of pathoadaptive mutations in virulence factors potentially linked to the development of chronic infections in CF.

Conclusions: The genome plasticity of P. aeruginosa particularly in the RP73 strain strongly indicated that these alterations may form the genetic basis defining host-bacteria interactions leading to a persistent lifestyle in human lungs.

No MeSH data available.


Related in: MedlinePlus