Fluoxetine and thioridazine inhibit efflux and attenuate crystalline biofilm formation by Proteus mirabilis.
Fluoxetine and thioridazine inhibit efflux and attenuate crystalline biofilm formation by Proteus mirabilis.
复制标题
氟西汀和硫利达嗪抑制奇异变形杆菌的外流并减弱结晶生物膜的形成。
DOI：
10.1038/s41598-017-12445-w
复制
发表时间：
2017-09-22
影响因子：
4.6
通讯作者：
Jones BV
中科院分区：
文献类型：
--
作者：
Nzakizwanayo J;Scavone P;Jamshidi S;Hawthorne JA;Pelling H;Dedi C;Salvage JP;Hind CK;Guppy FM;Barnes LM;Patel BA;Rahman KM;Sutton MJ;Jones BV
奇异变形杆菌在留置导尿管上形成大量结晶生物膜，阻塞尿液流动并导致严重的临床并发症。Bcr/CflA外排系统先前已被确定对奇异变形杆菌结晶生物膜的形成很重要，这凸显了外排泵抑制剂（EPIs）控制导尿管堵塞的潜力。在此，我们评估了已用于人类医学的药物（氟西汀和硫利达嗪）作为奇异变形杆菌中外排泵抑制剂以及控制结晶生物膜形成的潜力。氟西汀和硫利达嗪均抑制奇异变形杆菌的外排，并且分子模拟预测这两种药物都与生物膜相关的Bcr/CflA外排系统强烈相互作用。还发现这两种外排泵抑制剂都能显著降低奇异变形杆菌在导尿管上形成结晶生物膜的速率，并增加导尿管堵塞所需的时间。这两种外排泵抑制剂也显著降低了奇异变形杆菌的游动和群集运动能力。还探讨了这些药物对其他尿路病原体（大肠杆菌、铜绿假单胞菌）在导尿管上形成生物膜的影响，结果表明硫利达嗪也能抑制这些菌种的生物膜形成。因此，重新利用具有外排泵抑制活性的现有药物可能是控制导尿管堵塞或其他医疗器械上生物膜形成的一种有前景的方法。
Proteus mirabilis forms extensive crystalline biofilms on indwelling urethral catheters that block urine flow and lead to serious clinical complications. The Bcr/CflA efflux system has previously been identified as important for development of P. mirabilis crystalline biofilms, highlighting the potential for efflux pump inhibitors (EPIs) to control catheter blockage. Here we evaluate the potential for drugs already used in human medicine (fluoxetine and thioridazine) to act as EPIs in P. mirabilis, and control crystalline biofilm formation. Both fluoxetine and thioridazine inhibited efflux in P. mirabilis, and molecular modelling predicted both drugs interact strongly with the biofilm-associated Bcr/CflA efflux system. Both EPIs were also found to significantly reduce the rate of P. mirabilis crystalline biofilm formation on catheters, and increase the time taken for catheters to block. Swimming and swarming motilies in P. mirabilis were also significantly reduced by both EPIs. The impact of these drugs on catheter biofilm formation by other uropathogens (Escherichia coli, Pseudomonas aeruginosa) was also explored, and thioridazine was shown to also inhibit biofilm formation in these species. Therefore, repurposing of existing drugs with EPI activity could be a promising approach to control catheter blockage, or biofilm formation on other medical devices.
登录
查看更多内容
影响因子：
3.4
作者：
De Soyza, Anthony;Hall, Amanda J.;Mahenthiralingam, Eshwar;Drevinek, Pavel;Kaca, Wieslaw;Drulis-Kawa, Zuzanna;Stoitsova, Stoyanka R.;Toth, Veronika;Coenye, Tom;Zlosnik, James E. A.;Burns, Jane L.;Sa-Correia, Isabel;De Vos, Daniel;Pirnay, Jean-Paul;Kidd, Timothy J.;Reid, David;Manos, Jim;Klockgether, Jens;Wiehlmann, Lutz;Tuemmler, Burkhard;McClean, Siobhan;Winstanley, Craig
通讯作者：
Winstanley, Craig
影响因子：
5.6
作者：
JONES, G;WILLETT, P;GLEN, RC
通讯作者：
GLEN, RC
影响因子：
4.9
作者：
Kaatz, GW;Moudgal, VV;Kristiansen, JE
通讯作者：
Kristiansen, JE
影响因子：
6.6
作者：
COX, AJ;HUKINS, DWL
通讯作者：
HUKINS, DWL
影响因子：
3.1
作者：
JONES, BD;MOBLEY, HLT
通讯作者：
MOBLEY, HLT