Recipient Cell Factors Influence Interbacterial Competition Mediated by Two Distinct Burkholderia dolosa Contact-Dependent Growth Inhibition Systems.
Recipient Cell Factors Influence Interbacterial Competition Mediated by Two Distinct Burkholderia dolosa Contact-Dependent Growth Inhibition Systems.
复制标题
DOI：
10.1128/jb.00541-21
复制
发表时间：
2022-09-20
影响因子：
3.2
通讯作者：
中科院分区：
文献类型：
--
作者：
接触依赖性生长抑制（CDI）系统通过将一种大表面蛋白（在伯克霍尔德氏菌中称为BcpA）的有毒部分传递到邻近细菌的细胞质中，介导革兰氏阴性细菌之间的细菌间拮抗作用。抗菌多肽转运到受体细胞中需要特定的受体外膜和内膜蛋白，但这些因子在几种模式生物外的身份尚不清楚。为了鉴定与洋葱伯克氏菌复合体成员dolosa伯克氏菌CDI易感性相关的基因，采用转座子诱变选择方法富集对bpa -1或bpa -2耐药的突变体。随后的分析表明，候选调控基因对受体细胞对dolosa CDI的易感性有一定的影响。然而，大多数候选缺失突变体没有显示出与相应转座子突变体相同的表型。全基因组重测序显示，这些转座子突变体在三个基因位点（wabO、BDAG_01006和BDAG_01005）上也含有独特的突变，这些基因位点编码预测的脂多糖（LPS）生物合成酶。B. dolosa wabO、BDAG_01006和BDAG_01005突变体对CDI具有抗性，并产生具有改变的核心低聚糖和o抗原的LPS。尽管bpa -1和bpa -2是不同的，并且预期利用不同的外膜受体，但这两种蛋白的中毒同样受到LPS变化的影响。总之，这些发现表明，细胞调节的改变可能间接影响cdi介导的竞争效率，并证明LPS是两种不同的B. dolosa BcpA蛋白中毒所必需的。许多革兰氏阴性菌产生的接触依赖性生长抑制（CDI）系统蛋白是一种窄谱抗菌剂，可抑制密切相关的邻近细菌的生长。在这里，我们使用机会致病菌伯克氏菌来鉴定两种不同的CDI系统蛋白中毒所需的基因。我们的研究结果表明，CDI系统靶向的B. dolosa受体细胞只有在产生全长脂多糖时才会被陶醉。了解细菌间拮抗相互作用的机制可能有助于未来治疗的发展。
Contact-dependent growth inhibition (CDI) systems mediate interbacterial antagonism between Gram-negative bacteria by delivering the toxic portion of a large surface protein (termed BcpA in Burkholderia species) to the cytoplasm of neighboring bacteria. Translocation of the antibacterial polypeptide into recipient cells requires specific recipient outer and inner membrane proteins, but the identity of these factors outside several model organisms is unknown. To identify genes involved in CDI susceptibility in the Burkholderia cepacia complex member Burkholderia dolosa, a transposon mutagenesis selection approach was used to enrich for mutants resistant to BcpA-1 or BcpA-2. Subsequent analysis showed that candidate regulatory genes contributed modestly to recipient cell susceptibility to B. dolosa CDI. However, most candidate deletion mutants did not show the same phenotypes as the corresponding transposon mutants. Whole-genome resequencing revealed that these transposon mutants also contained unique mutations within a three gene locus (wabO, BDAG_01006, and BDAG_01005) encoding predicted lipopolysaccharide (LPS) biosynthesis enzymes. B. dolosa wabO, BDAG_01006, or BDAG_01005 mutants were resistant to CDI and produced LPS with altered core oligosaccharide and O-antigen. Although BcpA-1 and BcpA-2 are dissimilar and expected to utilize different outer membrane receptors, intoxication by both proteins was similarly impacted by LPS changes. Together, these findings suggest that alterations in cellular regulation may indirectly impact the efficiency of CDI-mediated competition and demonstrate that LPS is required for intoxication by two distinct B. dolosa BcpA proteins. IMPORTANCEContact-dependent growth inhibition (CDI) system proteins, produced by many Gram-negative bacteria, are narrow spectrum antimicrobials that inhibit the growth of closely related neighboring bacteria. Here, we use the opportunistic pathogen Burkholderia dolosa to identify genes required for intoxication by two distinct CDI system proteins. Our findings suggest that B. dolosa recipient cells targeted by CDI systems are only intoxicated if they produce full-length lipopolysaccharide. Understanding the mechanisms underlying antagonistic interbacterial interactions may contribute to future therapeutic development.
登录
查看更多内容
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
4.5
作者：
Anderson MS;Garcia EC;Cotter PA
通讯作者：
Cotter PA
影响因子：
3.7
作者：
Koskiniemi S;Garza-Sánchez F;Edman N;Chaudhuri S;Poole SJ;Manoil C;Hayes CS;Low DA
通讯作者：
Low DA
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
48
作者：
Choi, KH;Gaynor, JB;Schweizer, HP
通讯作者：
Schweizer, HP