近日,，國(guó)際著名雜志《細(xì)菌學(xué)雜志》Journal of Bacteriology上刊登了倫敦皇后瑪麗大學(xué)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，研究者揭示了綠膿桿菌的兩個(gè)I型信號(hào)肽酶LepB和PA1303，而且進(jìn)一步研究發(fā)現(xiàn),，這兩個(gè)肽酶在細(xì)菌的生理學(xué)和毒力上扮演著不同的角色。
I型信號(hào)肽酶(Type I signal peptidases,，SPases)是細(xì)菌細(xì)胞質(zhì)的膜結(jié)合酶,，可以清除分泌過(guò)程中異位蛋白質(zhì)的N端信號(hào)肽，SPases也是特殊的絲氨酸蛋白酶類,，可以催化絲氨酸-賴氨酸二聯(lián)體合成,。
在革蘭氏陰性菌中,，SPases介導(dǎo)的信號(hào)肽清除可以釋放蛋白質(zhì)進(jìn)入細(xì)胞周質(zhì)空間。在綠膿桿菌中,，其毒力因子包含了許多I型信號(hào)肽酶,，包括彈性蛋白酶LasA和LasB，外毒素A和β-內(nèi)酰胺酶AmpC等,，而且I型信號(hào)肽酶在綠膿桿菌的毒力發(fā)揮上扮演著重要角色,。
在文章中，研究者通過(guò)在綠膿桿菌基因組進(jìn)行Spase類似物比對(duì),，發(fā)現(xiàn)了基因lepB和PA1303具有信號(hào)肽酶的功能,，進(jìn)一步研究發(fā)現(xiàn)，LepB擁有了革蘭氏陰性菌所有的SPase,，而基因PA1303和細(xì)菌的毒力有密切關(guān)系,。最后作者表示，這兩個(gè)基因具有分子信號(hào)肽酶的功能,，而且對(duì)于綠膿桿菌的生理功能和毒力發(fā)揮必不可少,，而且未來(lái)這兩個(gè)基因有可能是新藥的研發(fā)靶點(diǎn)。（生物谷Bioon.com）
doi:10.1128/JB.06678-11
PMC:
PMID:
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.
