Mifepristone Increases Life Span in Female Drosophila Without Detectable Antibacterial Activity.
Mifepristone Increases Life Span in Female Drosophila Without Detectable Antibacterial Activity.
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DOI：
10.3389/fragi.2022.924957
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发表时间：
2022
影响因子：
--
通讯作者：
Tower, John
中科院分区：
文献类型：
--
作者：
Landis, Gary N.;Riggan, Luke;Bell, Hans S.;Vu, William;Wang, Tianyi;Wang, Ina;Tejawinata, Felicia I.;Ko, Sebastian;Tower, John
米非司酮可显着延长交配雌性果蝇的寿命，同时减少先天免疫反应基因的表达。先前的结果表明，米非司酮还减少了交配雌性体内耐氧细菌的负荷。进行实验是为了进一步研究细菌在米非司酮寿命影响中的可能作用。在两个独立的测定中，对高压灭菌培养基上的灭菌卵生长的果蝇和正常培养的对照果蝇的寿命进行了测定。绝育延长了交配雌性的寿命（分别+8.3%和+57%），米非司酮的效果是相加的（分别+53%和+93%）。 16S 序列的高通量测序表明，灭菌降低了多种物种以及拟杆菌、杆菌、放线菌和噬细胞菌的丰度。相比之下，米非司酮并没有导致三种物种的丰度减少，反而增加了。从交配雌性果蝇的提取物中培养出五种耐氧细菌，包括革兰氏阳性菌和革兰氏阴性菌（醋杆菌、粪肠球菌、植物乳杆菌、红沙雷氏菌和解葡糖类芽孢杆菌）。在体外没有检测到米非司酮对这些细菌生长的影响，表明米非司酮不具有直接的抗生素作用。为了测试抗生素是否可以在体内模拟米非司酮的作用，在重复实验中，在整个成年寿命中用高浓度的单独抗生素强力霉素、氨苄青霉素、卡那霉素和链霉素治疗交配的雌性果蝇。氨苄西林、卡那霉素或链霉素对寿命没有显着影响，而强力霉素的益处却不一致。最后，在存在或不存在米非司酮的情况下，补充粪肠球菌培养基不会改变成年女性的寿命。总而言之，结果表明米非司酮的寿命延长并不是由于抗生素的作用。
Mifepristone dramatically increases the life span of mated female Drosophila while reducing the expression of innate immune response genes. Previous results indicated that mifepristone also reduced the load of aero-tolerant bacteria in mated females. Experiments were conducted to further investigate the possible role of bacteria in mifepristone life span effects. Life span was assayed in flies grown from sterilized eggs on autoclaved media and in normally cultured controls in two independent assays. Sterilization increased mated female life span (+8.3% and +57%, respectively), and the effect of mifepristone was additive (+53% and +93%, respectively). High-throughput sequencing of 16S sequences revealed that sterilization reduced the abundance of multiple species and the classes Bacteroidia, Bacilli, Actinobacteria, and Cytophagia. By contrast, mifepristone caused no decreases and instead increased the abundance of three species. Five aero-tolerant bacterial species were cultured from extracts of mated female flies, including both Gram-positive and Gram-negative species (Acetobacter sicerae, Enterococcus faecalis, Lactobacillus plantarum, Serratia rubidea, and Paenibacillus glucanolyticus). There was no detectable effect of mifepristone on the growth of these bacteria in vitro, indicating that mifepristone does not have a direct antibiotic effect. To test if antibiotics could mimic the effects of mifepristone in vivo, mated female flies were treated throughout adult life span with high concentrations of the individual antibiotics doxycycline, ampicillin, kanamycin, and streptomycin, in replicate experiments. No significant effect on life span was observed for ampicillin, kanamycin, or streptomycin, and an inconsistent benefit was observed for doxycycline. Finally, supplementation of media with Enterococcus faecalis did not alter adult female life span in the presence or absence of mifepristone. Taken together, the results indicate the life span benefits of mifepristone are not due to an antibiotic effect.
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影响因子：
8.8
作者：
Clark RI;Salazar A;Yamada R;Fitz-Gibbon S;Morselli M;Alcaraz J;Rana A;Rera M;Pellegrini M;Ja WW;Walker DW
通讯作者：
Walker DW
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
影响因子：
12.3
作者：
Curtis C;Landis GN;Folk D;Wehr NB;Hoe N;Waskar M;Abdueva D;Skvortsov D;Ford D;Luu A;Badrinath A;Levine RL;Bradley TJ;Tavaré S;Tower J
通讯作者：
Tower J
影响因子：
4.5
作者：
Chen SJ;Shu HY;Lin GH
通讯作者：
Lin GH
影响因子：
6.4
作者：
Broderick NA;Buchon N;Lemaitre B
通讯作者：
Lemaitre B