Optimised chronic infection models demonstrate that siderophore 'cheating' in Pseudomonas aeruginosa is context specific.
Optimised chronic infection models demonstrate that siderophore 'cheating' in Pseudomonas aeruginosa is context specific.
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DOI：
10.1038/ismej.2017.103
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Diggle SP
中科院分区：
文献类型：
--
作者：
Harrison F;McNally A;da Silva AC;Heeb S;Diggle SP
铜绿假单胞菌铁载体突变体在感染过程中减弱毒力的潜力，以及利用这一点用于临床目的的可能性，吸引了许多讨论。这在很大程度上是基于在铁限制生长培养基中进行的体外实验的结果，其中铁载体突变体充当社会'骗子'：以野生型为代价增加频率，导致突变体占主导地位的低生产力，低毒性群体。我们表明，从体外实验的见解不一定转移到感染的情况下。首先，大多数已发表的实验使用未定义的铁载体突变体。该菌株的全基因组测序揭示了一系列影响铁载体生产以外的表型的突变。其次，铁限制培养基提供了与慢性感染中遇到的环境非常不同的环境。我们使用定义的铁载体缺失突变体，在设计用于模拟囊性纤维化肺部感染和不愈合伤口中感染的液体和组织的条件下进行了欺骗测定。根据不同的环境，铁载体的损失导致作弊，简单的健身缺陷，或根本没有健身效果。我们的研究结果表明，这是至关重要的，以预测铁载体是否是社会的，欺骗性的，并适合在特定的感染情况下的临床开发，开发定义的体外模型。
The potential for siderophore mutants of Pseudomonas aeruginosa to attenuate virulence during infection, and the possibility of exploiting this for clinical ends, have attracted much discussion. This has largely been based on the results of in vitro experiments conducted in iron-limited growth medium, in which siderophore mutants act as social ‘cheats:’ increasing in frequency at the expense of the wild type to result in low-productivity, low-virulence populations dominated by mutants. We show that insights from in vitro experiments cannot necessarily be transferred to infection contexts. First, most published experiments use an undefined siderophore mutant. Whole-genome sequencing of this strain revealed a range of mutations affecting phenotypes other than siderophore production. Second, iron-limited medium provides a very different environment from that encountered in chronic infections. We conducted cheating assays using defined siderophore deletion mutants, in conditions designed to model infected fluids and tissue in cystic fibrosis lung infection and non-healing wounds. Depending on the environment, siderophore loss led to cheating, simple fitness defects, or no fitness effect at all. Our results show that it is crucial to develop defined in vitro models in order to predict whether siderophores are social, cheatable and suitable for clinical exploitation in specific infection contexts.
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影响因子：
5.4
作者：
Brockhurst MA;Buckling A;Racey D;Gardner A
通讯作者：
Gardner A
影响因子：
5.2
作者：
Arai H
通讯作者：
Arai H
影响因子：
6.7
作者：
Flynn, Jeffrey M.;Niccum, David;Hunter, Ryan C.
通讯作者：
Hunter, Ryan C.
影响因子：
6.4
作者：
Cowley ES;Kopf SH;LaRiviere A;Ziebis W;Newman DK
通讯作者：
Newman DK
DOI：
10.1073/pnas.1508324112
发表时间：
2015-08-25
影响因子：
11.1
作者：
Andersen, Sandra Breum;Marvig, Rasmus Lykke;Griffin, Ashleigh S.
通讯作者：
Griffin, Ashleigh S.