Escherichia coli BarA-UvrY regulates the pks island and kills Staphylococci via the genotoxin colibactin during interspecies competition.
Escherichia coli BarA-UvrY regulates the pks island and kills Staphylococci via the genotoxin colibactin during interspecies competition.
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DOI：
10.1371/journal.ppat.1010766
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发表时间：
2022-09
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
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伤口感染本质上通常是多种微生物、生物膜相关，因此对抗生素治疗具有耐受性，并且与愈合延迟相关。大肠杆菌和金黄色葡萄球菌是伤口感染中最常见的培养病原体。然而，人们对伤口感染期间大肠杆菌和金黄色葡萄球菌多种微生物相互作用的频率或后果知之甚少。在这里，我们展示了大肠杆菌通过基因毒素大肠杆菌素在体外和小鼠切除伤口模型中杀死葡萄球菌，包括金黄色葡萄球菌。大肠杆菌素生物合成由 pks 基因座编码，我们在近 30% 的人类大肠杆菌伤口感染分离株中发现了该基因座。虽然尚不清楚大肠杆菌素如何从大肠杆菌中释放或如何渗透靶细胞，但我们发现大肠杆菌素中间体 N-肉豆蔻酰-D-Asn (NMDA) 会破坏金黄色葡萄球菌膜。我们还表明，BarA-UvrY 二组分系统 (TCS) 可以感知大肠杆菌和金黄色葡萄球菌混合物种相互作用期间产生的环境，从而导致 pks 岛基因上调。此外，我们还发现 BarA-UvrY 通过碳储存全局调节 (Csr) 系统来控制 pks 表达。总之，我们的数据证明了大肠杆菌素在种间竞争中的作用，并表明它在种间竞争过程中受到 BarA-UvrY TCS 的调节。伤口感染本质上通常是多种微生物感染，并且与疾病预后不良有关。大肠杆菌和金黄色葡萄球菌是伤口感染培养最多的五种病原体之一。然而，人们对伤口感染期间大肠杆菌和金黄色葡萄球菌之间的多种微生物相互作用知之甚少。在这项研究中，我们表明大肠杆菌通过基因毒素大肠杆菌素在体外和小鼠切除伤口模型中杀死金黄色葡萄球菌。我们还表明，BarA-UvrY 二组分系统 (TCS) 在这种混合物种相互作用过程中调节 pks 岛，通过碳储存全局调节 (Csr) 系统控制大肠杆菌素的产生。总之，我们的数据证明了大肠杆菌素在种间竞争中的作用，并表明它在种间竞争过程中受到 BarA-UvrY TCS 的调节。
Wound infections are often polymicrobial in nature, biofilm associated and therefore tolerant to antibiotic therapy, and associated with delayed healing. Escherichia coli and Staphylococcus aureus are among the most frequently cultured pathogens from wound infections. However, little is known about the frequency or consequence of E. coli and S. aureus polymicrobial interactions during wound infections. Here we show that E. coli kills Staphylococci, including S. aureus, both in vitro and in a mouse excisional wound model via the genotoxin, colibactin. Colibactin biosynthesis is encoded by the pks locus, which we identified in nearly 30% of human E. coli wound infection isolates. While it is not clear how colibactin is released from E. coli or how it penetrates target cells, we found that the colibactin intermediate N-myristoyl-D-Asn (NMDA) disrupts the S. aureus membrane. We also show that the BarA-UvrY two component system (TCS) senses the environment created during E. coli and S. aureus mixed species interaction, leading to upregulation of pks island genes. Further, we show that BarA-UvrY acts via the carbon storage global regulatory (Csr) system to control pks expression. Together, our data demonstrate the role of colibactin in interspecies competition and show that it is regulated by BarA-UvrY TCS during interspecies competition. Wound infections are often polymicrobial in nature and are associated with poor disease prognoses. Escherichia coli and Staphylococcus aureus are among the top five most cultured pathogens from wound infections. However, little is known about the polymicrobial interactions between E. coli and S. aureus during wound infections. In this study, we show that E. coli kills S. aureus both in vitro and in a mouse excisional wound model via the genotoxin, colibactin. We also show that the BarA-UvrY two component system (TCS) regulates the pks island during this mixed species interaction, acting through the carbon storage global regulatory (Csr) system to control colibactin production. Together, our data demonstrate the role of colibactin in interspecies competition and show that it is regulated by BarA-UvrY TCS during interspecies competition.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
6.7
作者：
Friedman DB;Stauff DL;Pishchany G;Whitwell CW;Torres VJ;Skaar EP
通讯作者：
Skaar EP
影响因子：
3.2
作者：
Folsom, James Patrick;Parker, Albert E.;Carlson, Ross P.
通讯作者：
Carlson, Ross P.
影响因子：
3.2
作者：
Bian, Xiaoying;Fu, Jun;Mueller, Rolf
通讯作者：
Mueller, Rolf
影响因子：
11.5
作者：
Bonnet, Mathilde;Buc, Emmanuel;Darfeuille-Michaud, Arlette
通讯作者：
Darfeuille-Michaud, Arlette