Systematic identification of molecular mediators of interspecies sensing in a community of two frequently coinfecting bacterial pathogens.
Systematic identification of molecular mediators of interspecies sensing in a community of two frequently coinfecting bacterial pathogens.
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DOI：
10.1371/journal.pbio.3001679
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发表时间：
2022-06
期刊：
影响因子：
9.8
通讯作者：
中科院分区：
文献类型：
--
作者：
细菌通常存在于动态的多物种群落中，其中多微生物相互作用影响适合度。阐明这些相互作用的分子机制对于理解和调节自然环境中的细菌行为至关重要。虽然细菌对外来物种的反应经常在分子和表型水平上表征，但引起这些反应的外源分子研究不足。在这里，我们概述了一个系统的策略，转录组学的基础上结合基因和生化筛选的启动子报告，以确定从一个物种的分子，被另一个。我们利用这种方法来研究病原体铜绿假单胞菌和金黄色葡萄球菌之间的相互作用，经常发现在合并感染。我们发现，铜绿假单胞菌感觉到不同的葡萄球菌外产物，包括金属载体葡萄球菌（StP），中间代谢产物柠檬酸盐和乙偶姻，以及调节其铁饥饿反应的多种分子。我们观察到StP抑制生物膜形成，并且铜绿假单胞菌可以利用柠檬酸盐和乙偶姻进行生长，揭示了这些相互作用具有拮抗作用和有益作用。由于我们方法的无偏性，我们还在基因组规模上鉴定了S.金黄色葡萄球菌，影响生产的每一个感测外产物，提供可能的目标，以修改多物种群落动态。此外，这些鉴定的S.金黄色葡萄球菌产物概括了铜绿假单胞菌对S.金黄色葡萄球菌上清液，验证我们的筛选策略。囊性纤维化（CF）的临床分离的两个S。金黄色葡萄球菌和铜绿假单胞菌也分别显示不同程度的诱导或应答，这表明这些相互作用在致病菌株中广泛存在。因此，我们的筛选方法鉴定了多个S。金黄色葡萄球菌分泌的分子被铜绿假单胞菌感知并影响其生理学，证明了这种方法的有效性，并对这两个物种之间相互作用的分子基础产生了新的见解。细菌通常存在于动态的多物种群落中，其中多微生物相互作用影响适合度。本研究使用无偏的基因组规模的方法来揭示多种金黄色葡萄球菌分泌的因子，被铜绿假单胞菌感知，具有竞争性和有利的后果。
Bacteria typically exist in dynamic, multispecies communities where polymicrobial interactions influence fitness. Elucidating the molecular mechanisms underlying these interactions is critical for understanding and modulating bacterial behavior in natural environments. While bacterial responses to foreign species are frequently characterized at the molecular and phenotypic level, the exogenous molecules that elicit these responses are understudied. Here, we outline a systematic strategy based on transcriptomics combined with genetic and biochemical screens of promoter-reporters to identify the molecules from one species that are sensed by another. We utilized this method to study interactions between the pathogens Pseudomonas aeruginosa and Staphylococcus aureus that are frequently found in coinfections. We discovered that P. aeruginosa senses diverse staphylococcal exoproducts including the metallophore staphylopine (StP), intermediate metabolites citrate and acetoin, and multiple molecules that modulate its iron starvation response. We observed that StP inhibits biofilm formation and that P. aeruginosa can utilize citrate and acetoin for growth, revealing that these interactions have both antagonistic and beneficial effects. Due to the unbiased nature of our approach, we also identified on a genome scale the genes in S. aureus that affect production of each sensed exoproduct, providing possible targets to modify multispecies community dynamics. Further, a combination of these identified S. aureus products recapitulated a majority of the transcriptional response of P. aeruginosa to S. aureus supernatant, validating our screening strategy. Cystic fibrosis (CF) clinical isolates of both S. aureus and P. aeruginosa also showed varying degrees of induction or responses, respectively, which suggests that these interactions are widespread among pathogenic strains. Our screening approach thus identified multiple S. aureus secreted molecules that are sensed by P. aeruginosa and affect its physiology, demonstrating the efficacy of this approach, and yielding new insight into the molecular basis of interactions between these two species. Bacteria typically exist in dynamic, multispecies communities where polymicrobial interactions influence fitness. This study uses an unbiased genome-scale approach to reveal multiple Staphylococcus aureus secreted factors that are sensed by Pseudomonas aeruginosa, with both competitive and favorable consequences.
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影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
影响因子：
6.4
作者：
Dunphy LJ;Grimes KL;Wase N;Kolling GL;Papin JA
通讯作者：
Papin JA
影响因子：
5.2
作者：
Carvalho SM;de Jong A;Kloosterman TG;Kuipers OP;Saraiva LM
通讯作者：
Saraiva LM
DOI：
10.1128/aem.6.4.241-246.1958
发表时间：
1958-01-01
期刊：
APPLIED MICROBIOLOGY
影响因子：
--
作者：
ELLIOTT, RP
通讯作者：
ELLIOTT, RP
影响因子：
6.4
作者：
Fey PD;Endres JL;Yajjala VK;Widhelm TJ;Boissy RJ;Bose JL;Bayles KW
通讯作者：
Bayles KW