Cross-Talk between Staphylococcus aureus and Other Staphylococcal Species via the agr Quorum Sensing System.
Cross-Talk between Staphylococcus aureus and Other Staphylococcal Species via the agr Quorum Sensing System.
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DOI：
10.3389/fmicb.2016.01733
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发表时间：
2016
影响因子：
5.2
通讯作者：
Ingmer H
中科院分区：
文献类型：
--
作者：
Canovas J;Baldry M;Bojer MS;Andersen PS;Grzeskowiak PK;Stegger M;Damborg P;Olsen CA;Ingmer H
葡萄球菌与人类和动物都有关。虽然大多数是非致病性的殖民者，但金黄色葡萄球菌是一种能够引起严重感染的机会性病原体。金黄色葡萄球菌的毒力是由agr群体感应系统控制的，该系统响应由AgrC（一种双组份组氨酸激酶）感知的分泌的自动诱导肽（AIPs）。在其他葡萄球菌物种中也发现了agr位点，对于表皮葡萄球菌，编码的AIP抑制金黄色葡萄球菌中agr调控的毒力基因的表达。在这项研究中，我们旨在更好地了解葡萄球菌和金黄色葡萄球菌之间的相互作用，并表明这种相互作用可能最终导致鉴定出新的针对金黄色葡萄球菌感染的抗毒候选物。在这里，我们展示了代表17种不同种类的52株葡萄球菌分离株中的37株的培养上清液抑制金黄色葡萄球菌agr。狗病原体施莱氏葡萄球菌表现出最有效的抑制活性，对金黄色葡萄球菌中发现的所有四种agr类都有活性。通过使用金黄色葡萄球菌菌株编码组成活性AIP受体，我们表明活性是通过agr介导的。随后对S. schleiferi AIP在金黄色葡萄球菌中的克隆和异种表达表明，该分子可能是抑制活性的原因，并且当纯合成S. schleiferi AIP能够完全消除金黄色葡萄球菌报告菌株的agr诱导时，进一步证明了这一点。为了评估对金黄色葡萄球菌毒力的影响，我们在体内将金黄色葡萄球菌和施莱氏葡萄球菌共同接种于mellongalleria wax moth幼虫，发现金黄色葡萄球菌关键毒力因子的表达被取消。我们的数据表明，金黄色葡萄球菌agr位点对其他葡萄球菌物种高度敏感，这表明agr是一种种间通信系统。基于这些结果，我们推测金黄色葡萄球菌与其他定殖葡萄球菌之间的相互作用将显著影响金黄色葡萄球菌引起感染的能力，并且我们提出其他葡萄球菌是可用于抗金黄色葡萄球菌感染的抗毒治疗的化合物的潜在来源。
Staphylococci are associated with both humans and animals. While most are non-pathogenic colonizers, Staphylococcus aureus is an opportunistic pathogen capable of causing severe infections. S. aureus virulence is controlled by the agr quorum sensing system responding to secreted auto-inducing peptides (AIPs) sensed by AgrC, a two component histidine kinase. agr loci are found also in other staphylococcal species and for Staphylococcus epidermidis, the encoded AIP represses expression of agr regulated virulence genes in S. aureus. In this study we aimed to better understand the interaction between staphylococci and S. aureus, and show that this interaction may eventually lead to the identification of new anti-virulence candidates to target S. aureus infections. Here we show that culture supernatants of 37 out of 52 staphylococcal isolates representing 17 different species inhibit S. aureus agr. The dog pathogen, Staphylococcus schleiferi, expressed the most potent inhibitory activity and was active against all four agr classes found in S. aureus. By employing a S. aureus strain encoding a constitutively active AIP receptor we show that the activity is mediated via agr. Subsequent cloning and heterologous expression of the S. schleiferi AIP in S. aureus demonstrated that this molecule was likely responsible for the inhibitory activity, and further proof was provided when pure synthetic S. schleiferi AIP was able to completely abolish agr induction of an S. aureus reporter strain. To assess impact on S. aureus virulence, we co-inoculated S. aureus and S. schleiferi in vivo in the Galleria mellonella wax moth larva, and found that expression of key S. aureus virulence factors was abrogated. Our data show that the S. aureus agr locus is highly responsive to other staphylococcal species suggesting that agr is an inter-species communication system. Based on these results we speculate that interactions between S. aureus and other colonizing staphylococci will significantly influence the ability of S. aureus to cause infection, and we propose that other staphylococci are potential sources of compounds that can be applied as anti-virulence therapy for combating S. aureus infections.