近日，国际著名杂志《细菌学杂志》Journal of Bacteriology上刊登了伦敦皇后玛丽大学的研究者的最新研究成果“Pseudomonas aeruginosa possesses two putative Type 1 signal peptidases ， LepB and PA1303，each with distinct roles in physiology and virulence”，文章中，研究者揭示了绿脓杆菌的两个I型信号肽酶LepB和PA1303，而且进一步研究发现，这两个肽酶在细菌的生理学和毒力上扮演着不同的角色。
I型信号肽酶(Type I signal peptidases，SPases)是细菌细胞质的膜结合酶，可以清除分泌过程中异位蛋白质的N端信号肽，SPases也是特殊的丝氨酸蛋白酶类，可以催化丝氨酸-赖氨酸二联体合成。
在革兰氏阴性菌中，SPases介导的信号肽清除可以释放蛋白质进入细胞周质空间。在绿脓杆菌中，其毒力因子包含了许多I型信号肽酶，包括弹性蛋白酶LasA和LasB，外毒素A和β-内酰胺酶AmpC等，而且I型信号肽酶在绿脓杆菌的毒力发挥上扮演着重要角色。
在文章中，研究者通过在绿脓杆菌基因组进行Spase类似物比对，发现了基因lepB和PA1303具有信号肽酶的功能，进一步研究发现，LepB拥有了革兰氏阴性菌所有的SPase，而基因PA1303和细菌的毒力有密切关系。最后作者表示，这两个基因具有分子信号肽酶的功能，而且对于绿脓杆菌的生理功能和毒力发挥必不可少，而且未来这两个基因有可能是新药的研发靶点。（生物谷Bioon.com）
doi:10.1128/JB.06678-11
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Pseudomonas aeruginosa possesses two putative Type 1 signal peptidases, LepB and PA1303, each with distinct roles in physiology and virulence
Richard D. Waite1,*, Ruth S. Rose2, Minnie Rangarajan1, Joseph Aduse-Opoku1, Ahmed Hashim1 and Michael A. Curtis1
Type I signal peptidases (SPases) cleave signal peptides from proteins during translocation across biological membranes and hence play a vital role in cellular physiology. SPase activity is also of fundamental importance to the pathogenesis of infection for many bacteria including Pseudomonas aeruginosa, which utilises a variety of secreted virulence factors including proteases and toxins. P. aeruginosa possesses two non-contiguous SPase homologues LepB (PA0768) and PA1303, which share 43% amino acid identity. RT-PCR showed that both proteases were expressed whilst a FRET-based assay using a peptide based on the signal sequence cleavage region of the secreted LasB elastase showed that recombinant LepB and PA1303 enzymes were both active. LepB is positioned within a genetic locus which resembles the locus containing the extensively characterized SPase of E. coli, and is of similar size and topology. It was also shown to be essential for viability and have high sequence identity with SPases from other pseudomonads (≥ 78%). In contrast PA1303, which is small for a Gram-negative SPase (20 kDa) was found to be dispensable. Mutation of PA1303 resulted in an altered protein secretion profile, increased N-butanoyl homoserine lactone production and influenced several quorum sensing controlled phenotypic traits, including swarming motility and the production of rhamnolipid and elastinolytic activity. These data indicate different cellular roles for these P. aeruginosa SPase paralogues; the role of PA1303 is integrated with the quorum sensing cascade and includes the suppression of virulence factor secretion and virulence associated phenotypes, whilst LepB is the primary SPase.
