Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore.
Singapore Centre for Environmental Life Sciences Engineering, Interdisciplinary Graduate Programme, Nanyang Technological University, Singapore, Singapore.
PLoS Pathog. 2022 Sep 6;18(9):e1010766. doi: 10.1371/journal.ppat.1010766. eCollection 2022 Sep.
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.
伤口感染通常具有多种微生物的特性，与生物膜相关，因此对抗生素治疗具有耐受性，并与愈合延迟有关。大肠杆菌和金黄色葡萄球菌是从伤口感染中最常培养的病原体。然而，对于大肠杆菌和金黄色葡萄球菌在伤口感染过程中多微生物相互作用的频率或后果知之甚少。在这里，我们通过肠毒素 colibactin 表明，大肠杆菌在体外和在小鼠切除性伤口模型中杀死包括金黄色葡萄球菌在内的葡萄球菌。colibactin 的生物合成由 pks 基因座编码，我们在近 30%的人类大肠杆菌伤口感染分离物中鉴定出了该基因座。虽然不清楚 colibactin 是如何从大肠杆菌中释放出来的，也不清楚它是如何穿透靶细胞的，但我们发现 colibactin 中间体 N-豆蔻酰-D-天冬氨酸（NMDA）破坏了金黄色葡萄球菌的膜。我们还表明，BarA-UvrY 双组分系统（TCS）感知大肠杆菌和金黄色葡萄球菌混合物种相互作用过程中产生的环境，导致 pks 岛基因的上调。此外，我们表明 BarA-UvrY 通过碳储存全局调节（Csr）系统发挥作用来控制 pks 的表达。总之，我们的数据表明了 colibactin 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 的调控。
