Daptomycin resistance in enterococci is associated with distinct alterations of cell membrane phospholipid content.
Daptomycin resistance in enterococci is associated with distinct alterations of cell membrane phospholipid content.
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DOI：
10.1371/journal.pone.0043958
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Arias CA
中科院分区：
文献类型：
--
作者：
Mishra NN;Bayer AS;Tran TT;Shamoo Y;Mileykovskaya E;Dowhan W;Guan Z;Arias CA
脂肽抗生素达托霉素（DAP）与细菌细胞膜（CM）相互作用。治疗期间粪肠球菌临床菌株中DAP耐药性的发展与编码参与细胞包膜稳态和磷脂代谢的酶的基因突变相关。在这里，我们的特点是CM磷脂谱的变化与临床肠球菌菌株的DAP耐药性的发展。用敏感和耐药的两对大肠杆菌临床株对，粪肠球菌（S613 vs.R712）和E.在DAP治疗前后恢复的屎肠细胞（S447 vs. R446）中，我们比较了四种不同的CM谱：磷脂含量、脂肪酸组成、膜流动性和被DAP透化和/或去极化的能力。此外，我们还对E.通过透射电子显微镜观察了两株菌对的细胞表面电荷，并测定了两株菌对的相对表面电荷。E.粪肠球菌E.屎肠主要含有4种磷脂酰甘油（PG）、心磷脂（cardiolipin）、赖氨酰磷脂酰甘油（L-PG）和甘油磷酸二糖二酰甘油（GP-DGDAG）。此外，E. faecalis CMs（而不是E.粪菌）还含有：i）磷脂酸;和ii）两种其它未知种类的含氨基PL。在两种肠球菌中DAP耐药性的发展与CM流动性和PG含量的显著降低以及GP-DGDAG的伴随增加相关。菌株对在其含氨基PL的外部CM易位（翻转）方面没有差异。脂肪酸含量在E. faecalis菌株对，而不饱和脂肪酸的显着减少，观察到在DAP抗性E。屎肠菌分离株R446（vsS 447）。E.屎囊与细胞被膜和细胞壁增厚的明显结构改变，以及DAP的去水化和透化CM的能力降低有关。PL含量和脂肪酸组成的明显改变与肠球菌DAP耐药性的发展相关。
The lipopeptide antibiotic, daptomycin (DAP) interacts with the bacterial cell membrane (CM). Development of DAP resistance during therapy in a clinical strain of Enterococcus faecalis was associated with mutations in genes encoding enzymes involved in cell envelope homeostasis and phospholipid metabolism. Here we characterized changes in CM phospholipid profiles associated with development of DAP resistance in clinical enterococcal strains. Using two clinical strain-pairs of DAP-susceptible and DAP-resistant E. faecalis (S613 vs. R712) and E. faecium (S447 vs. R446) recovered before and after DAP therapy, we compared four distinct CM profiles: phospholipid content, fatty acid composition, membrane fluidity and capacity to be permeabilized and/or depolarized by DAP. Additionally, we characterized the cell envelope of the E. faecium strain-pair by transmission electron microscopy and determined the relative cell surface charge of both strain-pairs. Both E. faecalis and E. faecium mainly contained four major CM PLs: phosphatidylglycerol (PG), cardiolipin, lysyl-phosphatidylglycerol (L-PG) and glycerolphospho-diglycodiacylglycerol (GP-DGDAG). In addition, E. faecalis CMs (but not E. faecium) also contained: i) phosphatidic acid; and ii) two other unknown species of amino-containing PLs. Development of DAP resistance in both enterococcal species was associated with a significant decrease in CM fluidity and PG content, with a concomitant increase in GP-DGDAG. The strain-pairs did not differ in their outer CM translocation (flipping) of amino-containing PLs. Fatty acid content did not change in the E. faecalis strain-pair, whereas a significant decrease in unsaturated fatty acids was observed in the DAP-resistant E. faecium isolate R446 (vs S447). Resistance to DAP in E. faecium was associated with distinct structural alterations of the cell envelope and cell wall thickening, as well as a decreased ability of DAP to depolarize and permeabilize the CM. Distinct alterations in PL content and fatty acid composition are associated with development of enterococcal DAP resistance.
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影响因子：
4.9
作者：
Hachmann, Anna-Barbara;Sevim, Elif;Helmann, John D.
通讯作者：
Helmann, John D.
影响因子：
3.1
作者：
Bayer, AS;Prasad, R;Yeaman, MR
通讯作者：
Yeaman, MR
DOI：
10.1016/0005-2760(75)90009-0
发表时间：
1975-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FISCHER, W;LANDGRAF, HR
通讯作者：
LANDGRAF, HR
DOI：
10.1016/0005-2760(73)90174-4
发表时间：
1973-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FISCHER, W;LANDGRAF, HR;HERRMANN, J
通讯作者：
HERRMANN, J
DOI：
10.1016/0005-2760(73)90113-6
发表时间：
1973-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FISCHER, W;ISHIZUKA, I;HERRMANN, J
通讯作者：
HERRMANN, J