Effect of Adaptive Changes of Lysophosphatidylethanolamine Content on Ampicillin Resistance of Yersinia Pseudotuberculosis

L. Davydova, N. Sanina, S. Bakholdina, A. Stenkova, A. Zabolotnaya
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Abstract

Most antibiotics are targeted at intracellular processes. Therefore, their effects are determined by an ability to penetrate bacterial membranes. Mechanism of reducing permeability of porin channels in Gram-negative bacteria is the least known one among the possible reasons of antibiotic resistance. The adaptive accumulation of lysophosphatidylethanolamine (LPE), which is observed under conditions typical for the parasitic phase (in particular, the availability of glucose) of Gram-negative bacteria Yersinia pseudotuberculsis is accompanied by rearrangements in conformation of outer membrane protein OmpF that may impede the porin channel permeability for ß-lactam antibiotics. In present study, we report that adaptive accumulation of LPE in membranes of Y. pseudotuberculosis grown in the presence of glucose reduces antibacterial effect of ampicillin. In turn, polyphenol extract from buckwheat husks (PEBH) induces both the decrease in the level of LPE and resistance of bacteria to ampicillin. Therefore, PEBH acts synergistically with ampicillin in vivo by lowering its MICs and therefore can be used as antibiotic adjuvant to improve an antibiotic's ability to cross the outer membrane. These results showed that strategies for regulation of adaptive changes in lipid matrix of bacterial membranes is a new potentially effective way to increase the sensitivity of pathogens to known antibiotics.
溶血磷脂酰乙醇胺含量的适应性变化对假结核耶尔森菌氨苄西林耐药性的影响
大多数抗生素是针对细胞内过程的。因此,它们的作用是由穿透细菌膜的能力决定的。革兰氏阴性菌的孔蛋白通道通透性降低的机制是目前尚不清楚的抗生素耐药原因之一。在典型的革兰氏阴性菌假结核耶尔森菌寄生期条件下(特别是葡萄糖的可用性)观察到溶血磷脂酰乙醇胺(LPE)的适应性积累伴随着外膜蛋白OmpF构象的重排,这可能阻碍ß-内酰胺类抗生素的孔蛋白通道渗透性。在目前的研究中,我们报道了在葡萄糖存在下生长的假结核杆菌膜中LPE的适应性积累降低了氨苄西林的抗菌作用。反过来,荞麦壳多酚提取物(PEBH)诱导LPE水平的降低和细菌对氨苄西林的耐药性。因此,PEBH在体内通过降低其mic与氨苄西林协同作用,因此可以用作抗生素佐剂,以提高抗生素穿过外膜的能力。这些结果表明,调控细菌膜脂质基质适应性变化的策略可能是提高病原体对已知抗生素敏感性的一种新的有效途径。
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