Genomic analysis reveals that Pseudomonas aeruginosa virulence is combinatorial

被引:429
作者
Lee, Daniel G.
Urbach, Jonathan M.
Wu, Gang
Liberati, Nicole T.
Feinbaum, Rhonda L.
Miyata, Sachiko
Diggins, Lenard T.
He, Jianxin
Saucier, Maude
Deziel, Eric
Friedman, Lisa
Li, Li
Grills, George
Montgomery, Kate
Kucherlapati, Raju
Rahme, Laurence G.
Ausubel, Frederick M.
机构
[1] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA
[2] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA
[3] Envivo Pharmaceut Inc, Watertown, MA 02472 USA
[4] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA
[5] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA
[6] Harvard Univ, Sch Med, Partners Healthcare Ctr Genet & Genom, Cambridge, MA 02139 USA
关键词
D O I
10.1186/gb-2006-7-10-r90
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background: Pseudomonas aeruginosa is a ubiquitous environmental bacterium and an important opportunistic human pathogen. Generally, the acquisition of genes in the form of pathogenicity islands distinguishes pathogenic isolates from nonpathogens. We therefore sequenced a highly virulent strain of P. aeruginosa, PA14, and compared it with a previously sequenced (and less pathogenic) strain, PAO1, to identify novel virulence genes. Results: The PA14 and PAO1 genomes are remarkably similar, although PA14 has a slightly larger genome (6.5 megabses [Mb]) than does PAO1 (6.3 Mb). We identified 58 PA14 gene clusters that are absent in PAO1 to determine which of these genes, if any, contribute to its enhanced virulence in a Caenorhabditis elegans pathogenicity model. First, we tested 18 additional diverse strains in the C. elegans model and observed a wide range of pathogenic potential; however, genotyping these strains using a custom microarray showed that the presence of PA14 genes that are absent in PAO1 did not correlate with the virulence of these strains. Second, we utilized a full-genome nonredundant mutant library of PA14 to identify five genes (absent in PAO1) required for C. elegans killing. Surprisingly, although these five genes are present in many other P. aeruginosa strains, they do not correlate with virulence in C. elegans. Conclusion: Genes required for pathogenicity in one strain of P. aeruginosa are neither required for nor predictive of virulence in other strains. We therefore propose that virulence in this organism is both multifactorial and combinatorial, the result of a pool of pathogenicity-related genes that interact in various combinations in different genetic backgrounds.
引用
收藏
页数:14
相关论文
共 40 条
[1]   Comparative genomic structure of prokaryotes [J].
Bentley, SD ;
Parkhill, J .
ANNUAL REVIEW OF GENETICS, 2004, 38 :771-792
[2]   'Ready made' virulence and 'dual use' virulence factors in pathogenic environmental fungi -: the Cryptococcus neoformans paradigm [J].
Casadevall, A ;
Steenbergen, JN ;
Nosanchuk, JD .
CURRENT OPINION IN MICROBIOLOGY, 2003, 6 (04) :332-337
[3]   Identification of virulence genes in a pathogenic strain of Pseudomonas aeruginosa by representational difference analysis [J].
Choi, JY ;
Sifri, CD ;
Goumnerov, BC ;
Rahme, LG ;
Ausubel, FM ;
Calderwood, SB .
JOURNAL OF BACTERIOLOGY, 2002, 184 (04) :952-961
[4]   Improved microbial gene identification with GLIMMER [J].
Delcher, AL ;
Harmon, D ;
Kasif, S ;
White, O ;
Salzberg, SL .
NUCLEIC ACIDS RESEARCH, 1999, 27 (23) :4636-4641
[5]  
DORING D, 1993, PSEUDOMONAS AERUGINO, P245
[6]   Genome mosaicism is conserved but not unique in Pseudomonas aeruginosa isolates from the airways of young children with cystic fibrosis [J].
Ernst, RK ;
D'Argenio, DA ;
Ichikawa, JK ;
Bangera, MG ;
Selgrade, S ;
Burns, JL ;
Hiatt, P ;
McCoy, K ;
Brittnacher, M ;
Kas, A ;
Spencer, DH ;
Olson, MV ;
Ramsey, BW ;
Lory, S ;
Miller, SI .
ENVIRONMENTAL MICROBIOLOGY, 2003, 5 (12) :1341-1349
[7]   Consed: A graphical tool for sequence finishing [J].
Gordon, D ;
Abajian, C ;
Green, P .
GENOME RESEARCH, 1998, 8 (03) :195-202
[8]   Automated finishing with Autofinish [J].
Gordon, D ;
Desmarais, C ;
Green, P .
GENOME RESEARCH, 2001, 11 (04) :614-625
[9]   Pathogenicity islands of virulent bacteria: Structure, function and impact on microbial evolution [J].
Hacker, J ;
BlumOehler, G ;
Muhldorfer, I ;
Tschape, H .
MOLECULAR MICROBIOLOGY, 1997, 23 (06) :1089-1097
[10]   The broad host range pathogen Pseudomonas aeruginosa strain PA14 carries two pathogenicity islands harboring plant and animal virulence genes [J].
He, JX ;
Baldini, RL ;
Déziel, E ;
Saucier, M ;
Zhang, QH ;
Liberati, NT ;
Lee, D ;
Urbach, J ;
Goodman, HM ;
Rahme, LG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (08) :2530-2535