|Chen, Jianshun -|
|Lory, Stephen -|
Submitted to: Journal of Bacteriology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 26, 2010
Publication Date: N/A
Interpretive Summary: The lungs of patients with cystic fibrosis (CF) can be chronically colonized by a number of bacteria. Pseudomonas aeruginosa, a common environmental bacterium, is the most prominent CF pathogen. Persistent colonization of P. aeruginosa results in progressive lung damage and is the leading cause of morbidity and mortality in CF patients. After the initial colonization, P. aeruginosa undergo changes in their genetic makeup, a process called genome evolution, which allow them to better survive in the CF lungs. One of the significant methods for genome evolution involves the uptake of large blocks of DNA from other bacteria and inserting them into their own genomes, which gives rise to genomic or pathogenicity islands. This process is called horizontal gene transfer (HGT). HGT can have a significant and immediate impact on the organism’s phenotype and virulence, and therefore, it plays a significant role in bacterial genome evolution and pathoadaptation. In our previous study, we demonstrated the transfer of a large pathogenicity island PAPI-1 in P. aeruginosa population (Qiu et al 2006, Proc Natl Acad Sci USA 103:19830-19835). PAPI-1 is a cluster of 115 genes and some have been shown to be responsible for virulence phenotypes in a number of infection models. In this study, we elucidated the mechanism of acquisition of the large pathogenicity island PAPI-1 in the P. aeruginosa population. We reported that PAPI-1 is transferred by a conjugation mechanism via a novel type IVb pilus encoded on the island. The PAPI-1 encoded pilus is closely related to the conjugative apparatus of plasmid R64. This study enhances our understanding of the means used by P. aeruginosa to become a successful pathogen and contributes to improved methods and strategies for therapeutic intervention in CF.
Technical Abstract: Pseudomonas aeruginosa is a major cause of nosocomial infections, particularly in immunocompromised patients or in individuals with cystic fibrosis. The notable ability of P. aeruginosa to inhabit a broad range of environments including humans is in part due to its large and diverse genomic repertoire. The genomes of most strains contain a significant number of large and small genomic islands, including those carrying virulence determinants (pathogenicity islands). The pathogenicity island PAPI-1 of strain PA14 is a cluster of 115 genes and some have been shown to be responsible for virulence phenotypes in a number of infection models. We have previously demonstrated that PAPI-1 can be transferred to other P. aeruginosa strains following excision from the chromosome of the donor. Here we show that PAPI-1 is transferred into recipient P. aeruginosa by a conjugative mechanism, via a type IV pilus, encoded in PAPI-1 by a 10-gene cluster, which is closely related to the genes in the enterobacterial plasmid R64. We also demonstrate that the precursor of the major pilus subunit, PilS2, is processed by the chromosomally-encoded prepillin peptidase PilD but not its paralogue FppA. Our results suggest that the pathogenicity island PAPI-1 may have evolved by acquisition of a conjugation system but because of its dependence on an essential chromosomal determinant, its transfer is restricted to P. aeruginosa or other species capable of providing a functional prepilin peptidase. .