Is Quorum Sensing Interference a Viable Alternative to Treat Pseudomonas aeruginosa Infections?

Is Quorum Sensing Interference a Viable Alternative to Treat Pseudomonas aeruginosa Infections?
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DOI:
10.3389/fmicb.2016.01454
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发表时间:
2016
影响因子:
5.2
通讯作者:
García-Contreras R
García-Contreras R
中科院分区:
生物学2区
文献类型:
--
作者:
García-Contreras R

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群体感应(QS)协调铜绿假单胞菌中多种毒力因子的表达,因此其抑制已被假定为治疗其感染的新选择。特别是,QS干扰方法声称它们减弱细菌毒力而不直接减少细菌生长,并表明在体内免疫系统将控制感染。此外,由于在丰富培养基中进行的体外实验表明,干扰QS可降低毒力因子的产生,而不影响细菌生长,因此假设体内治疗将最大限度地减少耐药菌株的选择。因此,有效实施用于治疗铜绿假单胞菌感染的成功群体感应干扰(QSI)疗法的基本假设是:(i)QS仅在毒力基因的调节中发挥重要作用,但其不影响与生长相关的代谢过程,(ii)毒力因子的表达仅受QS正调节,(iii)体内毒力因子的抑制不影响细菌生长,(iv)受感染患者的免疫系统将能够摆脱感染,和(v)该治疗对活跃产生感染的菌株有效。然而,对于铜绿假单胞菌中的QSI,在过去几年中积累了大量的实验证据来反对大多数这些假设的有效性,这表明需要更好地了解其毒力及其在感染过程中的行为,以便设计真正可靠的QSI治疗替代方案来对抗这种显着的病原体。
Quorum sensing (QS) coordinates the expression of multiple virulence factors in Pseudomonas aeruginosa; hence its inhibition has been postulated as a new alternative to treat its infections. In particular, QS interference approaches claim that they attenuate bacterial virulence without directly decreasing bacterial growth and suggest that in vivo the immune system would control the infections. Moreover, since in vitro experiments performed in rich medium demonstrate that interfering with QS decreases the production of virulence factors without affecting bacterial growth it was assumed than in vivo therapies will minimize the selection of resistant strains. Therefore, the underlying assumptions toward an effective implementation of a successful Quorum sensing interference (QSI) therapy for treating P. aeruginosa infections are that (i) QS only exerts important effects in the regulation of virulence genes but it does not affect metabolic processes linked to growth, (ii) the expression of virulence factors is only positively regulated by QS, (iii) inhibition of virulence factors in vivo do not affect bacterial growth, (iv) the immune system of the infected patients will be able to get rid of the infections, and (v) the therapy will be effective in the strains that are actively producing the infections. Nevertheless, for QSI in P. aeruginosa, substantial experimental evidence against the validity of most of these assumptions has accumulated during the past years, suggesting that a far better understanding of its virulence and its behavior during infections is needed in order to design truly solid QSI therapeutic alternatives to combat this remarkable pathogen.
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