Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA.
Pellissippi State Community College, Natural and Behavioral Sciences Department, Knoxville, Tennessee, USA.
Appl Environ Microbiol. 2020 Oct 1;86(20). doi: 10.1128/AEM.01178-20.
is a Gram-positive bacterium that normally exists as an intestinal commensal in humans but is also a leading cause of nosocomial infections. Previous work noted that growth supplementation with serum induced tolerance to membrane-damaging agents, including the antibiotic daptomycin. Specific fatty acids found within serum could independently provide tolerance to daptomycin (protective fatty acids), yet some fatty acids found in serum did not and had negative effects on enterococcal physiology (nonprotective fatty acids). Here, we measured a wide array of physiological responses after supplementation with combinations of protective and nonprotective fatty acids to better understand how serum induces daptomycin tolerance. When cells were supplemented with either nonprotective fatty acid, palmitic acid, or stearic acid, there were marked defects in growth and morphology, but these defects were rescued upon supplementation with either protective fatty acid, oleic acid, or linoleic acid. Membrane fluidity decreased with growth in either palmitic or stearic acid alone but returned to basal levels when a protective fatty acid was supplied. Daptomycin tolerance could be induced if a protective fatty acid was provided with a nonprotective fatty acid, and some specific combinations protected as well as serum supplementation. While cell envelope charge has been associated with tolerance to daptomycin in other Gram-positive bacteria, we concluded that it does not correlate with the fatty acid-induced protection we observed. Based on these observations, we conclude that daptomycin tolerance by serum is driven by specific, protective fatty acids found within the fluid. With an increasing prevalence of antibiotic resistance in the clinic, we strive to understand more about microbial defensive mechanisms. A nongenetic tolerance to the antibiotic daptomycin was discovered in that results in the increased survival of bacterial populations after treatment with the drug. This tolerance mechanism likely synergizes with antibiotic resistance in the clinic. Given that this tolerance phenotype is induced by incorporation of fatty acids present in the host, it can be assumed that infections by this organism require a higher dose of antibiotic for successful eradication. The mixture of fatty acids in human fluids is quite diverse, with little understanding between the interplay of fatty acid combinations and the tolerance phenotype we observe. It is crucial to understand the effects of fatty acid combinations on physiology if we are to suppress the tolerance physiology in the clinic.
是一种革兰氏阳性菌，通常作为人类肠道共生菌存在，但也是医院获得性感染的主要原因。以前的工作表明，血清生长补充剂诱导了对膜损伤剂的耐受性，包括抗生素达托霉素。血清中发现的特定脂肪酸可以独立提供对达托霉素的耐受性（保护性脂肪酸），但血清中发现的一些脂肪酸没有，并且对肠球菌生理学有负面影响（非保护性脂肪酸）。在这里，我们测量了广泛的生理反应，这些反应是在补充保护性和非保护性脂肪酸组合后产生的，以更好地了解血清如何诱导达托霉素耐受性。当细胞用非保护性脂肪酸、棕榈酸或硬脂酸补充时，生长和形态会出现明显缺陷，但当用保护性脂肪酸、油酸或亚油酸补充时，这些缺陷会得到挽救。单独生长在棕榈酸或硬脂酸中会降低膜流动性，但当供应保护性脂肪酸时，膜流动性会恢复到基础水平。如果提供保护性脂肪酸，就可以诱导达托霉素耐受性，并且一些特定的组合与血清补充一样具有保护作用。虽然细胞膜电荷与其他革兰氏阳性菌对达托霉素的耐受性有关，但我们得出的结论是，它与我们观察到的脂肪酸诱导保护无关。基于这些观察结果，我们得出结论，血清中的达托霉素耐受性是由在液体中发现的特定保护性脂肪酸驱动的。随着临床抗生素耐药性的日益流行，我们努力更多地了解微生物防御机制。在 中发现了一种非遗传的抗生素达托霉素耐受性，导致在药物治疗后细菌种群的存活率增加。这种耐受机制可能与临床中的抗生素耐药性协同作用。鉴于这种耐受表型是通过整合宿主中存在的脂肪酸诱导的，可以假设该生物体的感染需要更高剂量的抗生素才能成功根除。人体液体中的脂肪酸混合物非常多样化，对于脂肪酸组合和我们观察到的耐受表型之间的相互作用知之甚少。如果我们要在临床上抑制耐受生理学，了解脂肪酸组合对 生理学的影响至关重要。
