Interference with Pseudomonas aeruginosa Quorum Sensing and Virulence by the Mycobacterial Pseudomonas Quinolone Signal Dioxygenase AqdC in Combination with the N-Acylhomoserine Lactone Lactonase QsdA
Interference with Pseudomonas aeruginosa Quorum Sensing and Virulence by the Mycobacterial Pseudomonas Quinolone Signal Dioxygenase AqdC in Combination with the N-Acylhomoserine Lactone Lactonase QsdA
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DOI：
10.1128/iai.00278-19
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发表时间：
2019-10-01
影响因子：
3.1
通讯作者：
Fetzner, Susanne
中科院分区：
文献类型：
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作者：
Birmes, Franziska S.;Saering, Ruth;Fetzner, Susanne
医院病原体铜绿假单胞菌通过复杂的群体感应网络调节其毒力，除了N-酰基高丝氨酸内酯外，还包括烷基喹诺酮信号分子2-庚基-3-羟基-4（1H）-喹诺酮（假单胞菌喹诺酮信号[PQS]）和2-庚基-4（1H）-喹诺酮（HHQ）。类分枝杆菌一种新出现的病原体，能够降解PQS和HHQ。在这里，我们表明，虽然M。红腹叶蝉亚种尽管PQS在与铜绿假单胞菌PAO 1共培养中降低，但这不足以淬灭毒力因子绿脓菌素、绿脓菌荧光素和鼠李糖脂的产生。然而，这些毒力因子的水平在铜绿假单胞菌PAO 1与重组M.红腹叶蝉亚种过量表达M.红腹叶蝉亚种这证实了AqdC作为群体淬灭酶的潜力。当细胞外加入铜绿假单胞菌培养物中时，AqdC淬灭烷基喹诺酮和绿脓菌素的产生，但诱导弹性蛋白酶水平的增加。当用QsdA（一种来自红串红球菌的使N-酰基高丝氨酸内酯信号失活的酶）补充铜绿假单胞菌培养物时，鼠李糖脂和弹性蛋白酶水平被淬灭，但HHQ和绿脓菌素合成被促进。因此，单一的群体淬灭酶，针对一个复杂的群体感应网络中的个别电路，也可能引起不希望的监管效果。在AqdC、QsdA或两种酶存在下生长的铜绿假单胞菌培养物的上清液对人上皮肺细胞的细胞毒性低于未处理培养物的上清液。此外，铜绿假单胞菌中aqdC和qsdA的组合导致铜绿假单胞菌暴露下秀丽隐杆线虫死亡率的下降。
The nosocomial pathogen Pseudomonas aeruginosa regulates its virulence via a complex quorum sensing network, which, besides N-acylhomoserine lactones, includes the alkylquinolone signal molecules 2-heptyl-3-hydroxy-4(1H)-quinolone (Pseudomonas quinolone signal [PQS]) and 2-heptyl-4(1H)-quinolone (HHQ). Mycobacteroides abscessus subsp. abscessus, an emerging pathogen, is capable of degrading the PQS and also HHQ. Here, we show that although M. abscessus subsp. abscessus reduced PQS levels in coculture with P. aeruginosa PAO1, this did not suffice for quenching the production of the virulence factors pyocyanin, pyoverdine, and rhamnolipids. However, the levels of these virulence factors were reduced in co-cultures of P. aeruginosa PAO1 with recombinant M. abscessus subsp. massiliense overexpressing the PQS dioxygenase gene aqdC of M. abscessus subsp. abscessus, corroborating the potential of AqdC as a quorum quenching enzyme. When added extracellularly to P. aeruginosa cultures, AqdC quenched alkylquinolone and pyocyanin production but induced an increase in elastase levels. When supplementing P. aeruginosa cultures with QsdA, an enzyme from Rhodococcus erythropolis which inactivates N-acylhomoserine lactone signals, rhamnolipid and elastase levels were quenched, but HHQ and pyocyanin synthesis was promoted. Thus, single quorum quenching enzymes, targeting individual circuits within a complex quorum sensing network, may also elicit undesirable regulatory effects. Supernatants of P. aeruginosa cultures grown in the presence of AqdC, QsdA, or both enzymes were less cytotoxic to human epithelial lung cells than supernatants of untreated cultures. Furthermore, the combination of both aqdC and qsdA in P. aeruginosa resulted in a decline of Caenorhabditis elegans mortality under P. aeruginosa exposure.