He Jianxin, Baldini Regina L, Déziel Eric, Saucier Maude, Zhang Qunhao, Liberati Nicole T, Lee Daniel, Urbach Jonathan, Goodman Howard M, Rahme Laurence G
Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114, USA.
Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2530-5. doi: 10.1073/pnas.0304622101.
The ubiquitous bacterium Pseudomonas aeruginosa is the quintessential opportunistic pathogen. Certain isolates infect a broad range of host organisms, from plants to humans. The pathogenic promiscuity of particular variants may reflect an increased virulence gene repertoire beyond the core P. aeruginosa genome. We have identified and characterized two P. aeruginosa pathogenicity islands (PAPI-1 and PAPI-2) in the genome of PA14, a highly virulent clinical isolate. The 108-kb PAPI-1 and 11-kb PAPI-2, which are absent from the less virulent reference strain PAO1, exhibit highly modular structures, revealing their complex derivations from a wide array of bacterial species and mobile elements. Most of the genes within these islands that are homologous to known genes occur in other human and plant bacterial pathogens. For example, PAPI-1 carries a complete gene cluster predicted to encode a type IV group B pilus, a well known adhesin absent from strain PAO1. However, >80% of the PAPI-1 DNA sequence is unique, and 75 of its 115 predicted ORF products are unrelated to any known proteins or functional domains. Significantly, many PAPI-1 ORFs also occur in several P. aeruginosa cystic fibrosis isolates. Twenty-three PAPI ORFs were mutated, and 19 were found to be necessary for full plant or animal virulence, with 11 required for both. The large set of "extra" virulence functions encoded by both PAPIs may contribute to the increased promiscuity of highly virulent P. aeruginosa strains, by directing additional pathogenic functions.
无处不在的铜绿假单胞菌是典型的机会致病菌。某些菌株能感染从植物到人类等广泛的宿主生物。特定变体的致病多样性可能反映出其毒力基因库超出了铜绿假单胞菌核心基因组。我们在高毒力临床分离株PA14的基因组中鉴定并表征了两个铜绿假单胞菌致病岛(PAPI-1和PAPI-2)。108kb的PAPI-1和11kb的PAPI-2在低毒力参考菌株PAO1中不存在,它们呈现出高度模块化的结构,揭示了它们从多种细菌物种和移动元件复杂衍生而来。这些岛内与已知基因同源的大多数基因存在于其他人类和植物细菌病原体中。例如,PAPI-1携带一个完整的基因簇,预计编码IV型B群菌毛,这是PAO1菌株中不存在的一种知名黏附素。然而,PAPI-1超过80%的DNA序列是独特的,其115个预测的ORF产物中有75个与任何已知蛋白质或功能域无关。值得注意的是,许多PAPI-1的ORF也存在于几种铜绿假单胞菌囊性纤维化分离株中。23个PAPI的ORF被突变,其中19个被发现对植物或动物的完全毒力是必需的,11个对两者都是必需的。两个致病岛编码的大量“额外”毒力功能可能通过指导额外的致病功能,导致高毒力铜绿假单胞菌菌株的致病多样性增加。