Relaxed specificity of BcpB transporters mediates interactions between Burkholderia cepacia complex contact-dependent growth inhibition systems.
Relaxed specificity of BcpB transporters mediates interactions between Burkholderia cepacia complex contact-dependent growth inhibition systems.
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DOI：
10.1128/msphere.00303-23
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发表时间：
2023-08-24
期刊：
影响因子：
4.8
通讯作者：
Garcia, Erin C.
中科院分区：
文献类型：
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作者：
Elery, Zaria K.;Myers-Morales, Tanya;Phillips, Erica D.;Garcia, Erin C.
关键词：
接触依赖性生长抑制（CDI）系统属于双体分泌蛋白家族，介导密切相关的革兰氏阴性菌之间的细菌间拮抗作用。一种大的表面蛋白BcpA/CdiA的毒性部分被递送到邻近细胞的细胞质中，在那里它抑制生长。将抗菌多肽转运出生产细胞需要相关的外膜转运蛋白BcpB/CdiB。一些细菌，包括许多伯克霍尔德菌属物种，编码多个不同的CDI系统，但这些系统之间是否存在相互作用在很大程度上是未知的。使用洋葱伯克霍尔德菌复合物种作为模型，我们发现相关的BcpB转运蛋白表现出相当大的分泌灵活性，并且可以分泌同源和非同源BcpA底物。我们还确定了一个额外的独特的Burkholderia dolosa CDI系统能够介导细菌间的竞争，并证明其BcpB转运蛋白具有类似的宽松的底物特异性。我们的结果表明，两个Bcp B转运蛋白（Bcp B-2和Bcp B-3）能够分泌所有四个B。dolosa BcpA毒素，而一种转运蛋白（BcpB-1）在测试条件下似乎甚至不能分泌其同源BcpA底物。这种灵活性提供了竞争优势，因为缺乏BcpB蛋白完整库的菌株具有降低的CDI活性。在多噬伯克霍尔德氏菌中获得了类似的结果，表明分泌灵活性可能是伯克霍尔德氏菌CDI系统的保守特征。总之，这些发现表明不同CDI系统之间的相互作用增强了细菌拮抗作用的效率。洋葱伯克霍尔德氏菌复合体（Bcc）是一组相关的机会性细菌病原体，占据了各种生态位，并加剧了基础疾病患者的疾病。革兰氏阴性菌产生的接触依赖性生长抑制（CDI）系统蛋白含有拮抗特性，可通过分泌蛋白BcpA使密切相关的邻近细菌中毒。多个独特的CDI系统可以在相同的细菌菌株中找到，在这里，我们表明，这些不同的系统在几个BCC物种相互作用。我们的研究结果表明，CDI系统蛋白之间的相互作用是重要的细菌间毒性。了解CDI系统之间的相互作用机制提供了进一步了解细菌拮抗作用的复杂性。此外，由于许多细菌物种被预测编码多个CDI系统，这项研究表明，这些不同的系统之间的相互作用可能有助于这些物种的整体竞争适应性。
Belonging to the two-partner secretion family of proteins, contact-dependent growth inhibition (CDI) systems mediate interbacterial antagonism among closely related Gram-negative bacteria. The toxic portion of a large surface protein, BcpA/CdiA, is delivered to the cytoplasm of neighboring cells where it inhibits growth. Translocation of the antibacterial polypeptide out of the producing cell requires an associated outer membrane transporter, BcpB/CdiB. Some bacteria, including many Burkholderia species, encode multiple distinct CDI systems, but whether there is interaction between these systems is largely unknown. Using Burkholderia cepacia complex species as a model, here we show that related BcpB transporters exhibit considerable secretion flexibility and can secrete both cognate and non-cognate BcpA substrates. We also identified an additional unique Burkholderia dolosa CDI system capable of mediating interbacterial competition and demonstrated that its BcpB transporter has similar relaxed substrate specificity. Our results showed that two BcpB transporters (BcpB-2 and BcpB-3) were able to secrete all four of the B. dolosa BcpA toxins, while one transporter (BcpB-1) appeared unable to secrete even its cognate BcpA substrate under the tested conditions. This flexibility provided a competitive advantage, as strains lacking the full repertoire of BcpB proteins had decreased CDI activity. Similar results were obtained in Burkholderia multivorans, suggesting that secretion flexibility may be a conserved feature of Burkholderia CDI systems. Together these findings suggest that the interaction between distinct CDI systems enhances the efficiency of bacterial antagonism. The Burkholderia cepacia complex (Bcc) is a group of related opportunistic bacterial pathogens that occupy a diverse range of ecological niches and exacerbate disease in patients with underlying conditions. Contact-dependent growth inhibition (CDI) system proteins, produced by Gram-negative bacteria, contain antagonistic properties that allow for intoxication of closely related neighboring bacteria via a secreted protein, BcpA. Multiple unique CDI systems can be found in the same bacterial strain, and here we show that these distinct systems interact in several Bcc species. Our findings suggest that the interaction between CDI system proteins is important for interbacterial toxicity. Understanding the mechanism of interplay between CDI systems provides further insight into the complexity of bacterial antagonism. Moreover, since many bacterial species are predicted to encode multiple CDI systems, this study suggests that interactions between these distinct systems likely contribute to the overall competitive fitness of these species.
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影响因子：
4.5
作者：
Anderson MS;Garcia EC;Cotter PA
通讯作者：
Cotter PA
影响因子：
7.7
作者：
Guerin J;Botos I;Zhang Z;Lundquist K;Gumbart JC;Buchanan SK
通讯作者：
Buchanan SK
影响因子：
3.7
作者：
Mercy C;Ize B;Salcedo SP;de Bentzmann S;Bigot S
通讯作者：
Bigot S
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
64.8
作者：
通讯作者：
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