The loss of the pyoverdine secondary receptor in Pseudomonas aeruginosa results in a fitter strain suitable for population invasion
The loss of the pyoverdine secondary receptor in Pseudomonas aeruginosa results in a fitter strain suitable for population invasion
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铜绿假单胞菌中pyoverdine二级受体的丧失导致了适合种群入侵的更适合的菌株
DOI：
10.1101/2020.05.08.085159
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
González J
中科院分区：
文献类型：
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作者：
González J
抗生素耐药细菌病原体的迅速出现构成了医疗保健中的一个关键问题，需要开发新的治疗方法。潜在的策略包括利用基于公共产品的微生物社会互动，这些公共产品是由合作微生物以适合度成本生产的，但可能被不生产这些产品的骗子利用。骗子入侵被认为是一种“特洛伊木马”方法，利用具有固有弱点（例如，对抗生素的敏感性）的菌株渗透病原体种群。然而，以前的尝试往往是不成功的，因为各种机制阻止了骗子的人口入侵，包括空间结构的存在（例如，生物膜的生长），这限制了公共产品的扩散和利用。在这里，我们采用了另一种方法，并研究了操纵公共产品的吸收而不是其生产是否会导致适合人口入侵的潜在“特洛伊木马”。我们重点研究了由人类病原体铜绿假单胞菌ampao1产生的铁载体pyoverdine，并通过删除和/或过表达pyoverdine初级（FpvA）和次级（FpvB）受体来控制其摄取。我们发现，受体的合成反馈到pyoverdine的生产和吸收速率，这导致菌株与pyoverdine相关的成本和收益发生变化。此外，我们发现受体FpvB在铁限制条件下是有利的，但在抗生素应激源（庆大霉素）存在时显示出隐藏的成本。结果，FpvB突变体在庆大霉素暴露下成为最适合的菌株，在液体培养物、生物膜和蜡蛾幼虫（蜡蛾幼虫）感染期间取代了野生型，这两者都代表了结构化环境。我们的研究结果表明，与多用途pyoverdine摄取策略的成本和收益相关的进化权衡可以用于设计医疗干预的特洛伊木马候选人。
The rapid emergence of antibiotic resistant bacterial pathogens constitutes a critical problem in healthcare and requires the development of novel treatments. Potential strategies include the exploitation of microbial social interactions based on public goods, which are produced at a fitness cost by cooperative microorganisms, but can be exploited by cheaters that do not produce these goods. Cheater invasion has been proposed as a ‘Trojan horse’ approach to infiltrate pathogen populations with strains deploying built-in weaknesses (e.g., sensitiveness to antibiotics). However, previous attempts have been often unsuccessful because population invasion by cheaters was prevented by various mechanisms including the presence of spatial structure (e.g., growth in biofilms), which limits the diffusion and exploitation of public goods. Here we followed an alternative approach and examined whether the manipulation of public good uptake and not its production could result in potential ‘Trojan horses’ suitable for population invasion. We focused on the siderophore pyoverdine produced by the human pathogenPseudomonas aeruginosaMPAO1 and manipulated its uptake by deleting and/or overexpressing the pyoverdine primary (FpvA) and secondary (FpvB) receptors. We found that receptor synthesis feeds back on pyoverdine production and uptake rates, which led to strains with altered pyoverdine-associated costs and benefits. Moreover, we found that the receptor FpvB was advantageous under iron-limited conditions but revealed hidden costs in the presence of an antibiotic stressor (gentamicin). As a consequence, FpvB mutants became the fittest strain under gentamicin exposure, displacing the wildtype in liquid cultures, and in biofilms and during infections of the wax moth larvaeGalleria mellonella, which both represent structured environments. Our findings reveal that an evolutionary trade-off associated with the costs and benefits of a versatile pyoverdine uptake strategy can be harnessed for devising a Trojan-horse candidate for medical interventions.