Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY, USA.
PLoS One. 2012;7(9):e45778. doi: 10.1371/journal.pone.0045778. Epub 2012 Sep 20.
Bacteria are well known to form dormant persister cells that are tolerant to most antibiotics. Such intrinsic tolerance also facilitates the development of multidrug resistance through acquired mechanisms. Thus persister cells are a promising target for developing more effective methods to control chronic infections and help prevent the development of multidrug-resistant bacteria. However, control of persister cells is still an unmet challenge.
METHODOLOGY/PRINCIPAL FINDINGS: We show in this report that (Z)-4-bromo-5-(bromomethylene)-3-methylfuran-2(5H)-one (BF8) can restore the antibiotic susceptibility of Pseudomonas aeruginosa PAO1 persister cells at growth non-inhibitory concentrations. Persister control by BF8 was found to be effective against both planktonic and biofilm cells of P. aeruginosa PAO1. Interestingly, although BF8 is an inhibitor of quorum sensing (QS) in Gram-negative bacteria, the data in this study suggest that the activities of BF8 to revert antibiotic tolerance of P. aeruginosa PAO1 persister cells is not through QS inhibition and may involve other targets.
BF8 can sensitize P. aeruginosa persister cells to antibiotics.
众所周知，细菌会形成休眠的持久生存细胞，对大多数抗生素具有耐受性。这种内在的耐受性也通过获得性机制促进了多药耐药性的发展。因此，持久生存细胞是开发更有效方法来控制慢性感染并帮助预防多药耐药细菌发展的有前途的目标。然而，控制持久生存细胞仍然是一个未满足的挑战。
方法/主要发现：我们在本报告中表明，（Z）-4-溴-5-（溴亚甲基）-3-甲基-2（5H）-呋喃酮（BF8）可以在非抑制生长浓度下恢复铜绿假单胞菌 PAO1 持久生存细胞对抗生素的敏感性。发现 BF8 对铜绿假单胞菌 PAO1 的浮游和生物膜细胞都具有持久生存控制作用。有趣的是，尽管 BF8 是革兰氏阴性菌群体感应（QS）的抑制剂，但本研究中的数据表明，BF8 使铜绿假单胞菌 PAO1 持久生存细胞对抗生素的耐受性逆转的活性不是通过 QS 抑制，可能涉及其他靶点。
BF8 可以使铜绿假单胞菌持久生存细胞对抗生素敏感。
