LPS remodeling is an evolved survival strategy for bacteria
LPS remodeling is an evolved survival strategy for bacteria
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LPS重塑是细菌进化的生存策略
DOI：
10.1073/pnas.1202908109
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发表时间：
2012-05-29
影响因子：
11.1
通讯作者：
Ernst, Robert K.
中科院分区：
文献类型：
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作者：
Li, Yanyan;Powell, Daniel A.;Ernst, Robert K.
膜功能的维持是必要的，并在基因组，转录和翻译水平上进行调节。细菌病原体具有多种机制来适应其膜以响应环境、媒介和人类宿主之间的传播。使用一个很好的特点模型的脂质A多样化（弗朗西斯），我们证明了温度调节膜重塑的脂质A修饰N-酰基转移酶，LpxD的多个等位基因。在环境和宿主温度下对脂质A的结构分析显示，LpxD 1酶在37 °C（宿主）下添加3-OH C18酰基，而LpxD 2酶在18 °C（环境）下添加3-OH C16酰基。任何一个单独的弗朗西斯lpxD基因的突变分析改变外膜（OM）的通透性，抗菌肽，抗生素的敏感性，而只有lpxD 1无效突变体在小鼠中被削弱，随后表现出对致命的野生型挑战的保护。此外，生长温度分析显示lpxD基因的转录控制和LpxD 1和LpxD 2酶活性的翻译后控制。这些结果表明，LPS/脂质A-水平的修改导致膜流动性的改变，以及完整性的直接机制，并可能代表细菌膜适应和耐受状态适应的一般范例。
Maintenance of membrane function is essential and regulated at the genomic, transcriptional, and translational levels. Bacterial pathogens have a variety of mechanisms to adapt their membrane in response to transmission between environment, vector, and human host. Using a well-characterized model of lipid A diversification (Francisella), we demonstrate temperature-regulated membrane remodeling directed by multiple alleles of the lipid A-modifying N-acyltransferase enzyme, LpxD. Structural analysis of the lipid A at environmental and host temperatures revealed that the LpxD1 enzyme added a 3-OH C18 acyl group at 37 °C (host), whereas the LpxD2 enzyme added a 3-OH C16 acyl group at 18 °C (environment). Mutational analysis of either of the individual Francisella lpxD genes altered outer membrane (OM) permeability, antimicrobial peptide, and antibiotic susceptibility, whereas only the lpxD1-null mutant was attenuated in mice and subsequently exhibited protection against a lethal WT challenge. Additionally, growth-temperature analysis revealed transcriptional control of the lpxD genes and posttranslational control of the LpxD1 and LpxD2 enzymatic activities. These results suggest a direct mechanism for LPS/lipid A-level modifications resulting in alterations of membrane fluidity, as well as integrity and may represent a general paradigm for bacterial membrane adaptation and virulence-state adaptation.