The blp bacteriocins of Streptococcus pneumoniae mediate intraspecies competition both in vitro and in vivo
The blp bacteriocins of Streptococcus pneumoniae mediate intraspecies competition both in vitro and in vivo
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DOI：
10.1128/iai.01775-05
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发表时间：
2007-01-01
影响因子：
3.1
通讯作者：
Weiser, Jeffrey N.
中科院分区：
文献类型：
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作者：
Dawid, Suzanne;Roche, Aoife M.;Weiser, Jeffrey N.
结合七价肺炎球菌疫苗的引入已导致非疫苗肺炎链球菌血清型取代疫苗血清型。这一观察表明，在鼻咽定植期间，肺炎球菌之间发生了种内竞争，允许一种或一组菌株凌驾于其他菌株之上。我们研究了编码细菌素和同源免疫肽的BLP基因座对种内竞争的贡献。我们在体外测序了一株能够抑制4型菌株TIGR4生长的6A型菌株的BLP基因座的相关区域。通过缺失分析，我们证实了抑制活性受反应调节因子BlpR的功能调节，并且需要两个可能的细菌素基因blpM和blpN。对TIGR4、BlpM和-N氨基酸序列的比较表明，只有5个氨基酸差异足以靶向该异源菌株。对一些临床分离株的分析表明，BlpMN细菌素分为两个家族。在临床相关的19A型背景中产生的blpMN操纵子中的一个突变体缺乏细菌素活性和免疫力。在小鼠鼻咽共定植期间，该菌株不能与其亲本菌株和4型分离物竞争，这表明该基因座在体内具有功能，并证实了其促进种内竞争的作用。
The introduction of the conjugate seven-vallent pneumococcal vaccine has led to the replacement of vaccine serotypes with nonvaccine serotypes of Streptococcus pneumoniae. This observation implies that intraspecies competition between pneumococci occurs during nasopharyngeall colonization, allowing one strain or set of strains to predominate over others. We investigated the contribution of the blp locus, encoding putative bacteriocins and cognate immunity peptides, to intraspecies competition. We sequenced the relevant regions of the blp locus of a type 6A strain able to inhibit the growth of the type 4 strain, TIGR4, in vitro. Using deletional analysis, we confirmed that inhibitory activity is regulated by the function of the response regulator, BlpR, and requires the two putative bacteriocin genes blpM and blpN. Comparison of the TIGR4 BlpM and -N amino acid sequences demonstrated that only five amino acid differences were sufficient to target the heterologous strain. Analysis of a number of clinical isolates suggested that the BlpMN bacteriocins divide into two families. A mutant in the blpMN operon created in the clinically relevant type 19A background was deficient in both bacteriocin activity and immunity. This strain was unable to compete with both its parent strain and a serotype 4 isolate during cocolonization in the mouse nasopharynx, suggesting that the locus is functional in vivo and confirming its role in promoting intraspecies competition.