Transcriptional attenuation controls macrolide inducible efflux and resistance in Streptococcus pneumoniae and in other Gram-positive bacteria containing mef/mel(msr(D)) elements.
Transcriptional attenuation controls macrolide inducible efflux and resistance in Streptococcus pneumoniae and in other Gram-positive bacteria containing mef/mel(msr(D)) elements.
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DOI：
10.1371/journal.pone.0116254
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Stephens DS
中科院分区：
文献类型：
--
作者：
Chancey ST;Bai X;Kumar N;Drabek EF;Daugherty SC;Colon T;Ott S;Sengamalay N;Sadzewicz L;Tallon LJ;Fraser CM;Tettelin H;Stephens DS
肺炎链球菌和其他革兰氏阳性菌中出现的大环内酯类耐药性越来越多地是由于在离散的移动的遗传元件上发现的mef/mel（msr）操纵子编码的外排泵所致。mef/mel（msr）在这些元素中的调节还不清楚。我们鉴定了mef（E）/mel转录起始点，定位了mef（E）/mel启动子，并证明转录减弱是S.肺炎。mef（E）/mel转录起始位点是mef（E）上游327 bp的鸟嘌呤。在起始位点上游7 bp处鉴定了肺炎球菌共有启动子-10（5′-TATACT-3′）和-35（5′-TTGAAC-3′）盒，它们相隔17 bp。对327 5'区的预测二级结构的分析鉴定了预测折叠成茎环的四对反向重复序列R1-R8、大环内酯诱导所需的小前导肽[MTASMRLR，（Mef（E）L）]和Rho非依赖性转录终止子。RNA-seq分析提供了转录衰减的确认。此外，mef（E）L的表达也受到mef（E）L依赖性mRNA稳定性的影响。mef（E）的调控区5'在其他含mef/mel（msr）的元件中高度保守，包括肺炎球菌中的Tn1207.1和5612 IQ复合物以及A组链球菌中的Tn1207.3，表明多种含mef/mel（msr）元件的革兰氏阳性菌共有的调控机制。
Macrolide resistance, emerging in Streptococcus pneumoniae and other Gram-positive bacteria, is increasingly due to efflux pumps encoded by mef/mel(msr) operons found on discrete mobile genetic elements. The regulation of mef/mel(msr) in these elements is not well understood. We identified the mef(E)/mel transcriptional start, localized the mef(E)/mel promoter, and demonstrated attenuation of transcription as a mechanism of regulation of macrolide-inducible mef-mediated macrolide resistance in S. pneumoniae. The mef(E)/mel transcriptional start site was a guanine 327 bp upstream of mef(E). Consensus pneumococcal promoter -10 (5′-TATACT-3′) and -35 (5′-TTGAAC-3′) boxes separated by 17 bp were identified 7 bp upstream of the start site. Analysis of the predicted secondary structure of the 327 5’ region identified four pairs of inverted repeats R1-R8 predicted to fold into stem-loops, a small leader peptide [MTASMRLR, (Mef(E)L)] required for macrolide induction and a Rho-independent transcription terminator. RNA-seq analyses provided confirmation of transcriptional attenuation. In addition, expression of mef(E)L was also influenced by mef(E)L-dependent mRNA stability. The regulatory region 5’ of mef(E) was highly conserved in other mef/mel(msr)-containing elements including Tn1207.1 and the 5612IQ complex in pneumococci and Tn1207.3 in Group A streptococci, indicating a regulatory mechanism common to a wide variety of Gram-positive bacteria containing mef/mel(msr) elements.
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DOI：
10.1093/bioinformatics/btp250
发表时间：
2009-08-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Darty K;Denise A;Ponty Y
通讯作者：
Ponty Y
影响因子：
6.7
作者：
Kwon, Ae-Ran;Min, Yu-Hong;Choi, Eung-Chil
通讯作者：
Choi, Eung-Chil
影响因子：
4.4
作者：
DUNNY, GM;LEE, LN;LEBLANC, DJ
通讯作者：
LEBLANC, DJ
DOI：
10.1073/pnas.84.2.498
发表时间：
1987-01-01
影响因子：
11.1
作者：
BECHHOFER, DH;DUBNAU, D
通讯作者：
DUBNAU, D
影响因子：
2.9
作者：
MCCASKILL, JS
通讯作者：
MCCASKILL, JS