Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, United States.
Emory Vaccine Center, Atlanta, GA, United States.
Front Cell Infect Microbiol. 2021 Nov 4;11:778331. doi: 10.3389/fcimb.2021.778331. eCollection 2021.
is a multidrug-resistant, Gram-negative nosocomial pathogen that exhibits phenotypic heterogeneity resulting in virulent opaque (VIR-O) and avirulent translucent (AV-T) colony variants. Each variant has a distinct gene expression profile resulting in multiple phenotypic differences. Cells interconvert between the VIR-O and AV-T variants at high frequency under laboratory conditions, suggesting that the genetic mechanism underlying the phenotypic switch could be manipulated to attenuate virulence. Therefore, our group has focused on identifying and characterizing genes that regulate this switch, which led to the investigation of (), a highly conserved gene predicted to encode a LysR-type transcriptional regulator. ABUW_1132 was shown to be a global regulator as the expression of 74 genes was altered ≥ 2-fold in an deletion mutant. The deletion also resulted in a 16-fold decrease in VIR-O to AV-T switching, loss of 3-OH-C-HSL secretion, and reduced surface-associated motility. Further, the deletion of in the AV-T background caused elevated capsule production, which increased colony opacity and altered the typical avirulent phenotype of translucent cells. These findings distinguish as a global regulatory gene and advance our understanding of 's opacity-virulence switch.
是一种多重耐药的革兰氏阴性医院病原体，表现出表型异质性，导致毒力 opaque（VIR-O）和无毒 translucent（AV-T）菌落变体。每种变体都有独特的基因表达谱，导致多种表型差异。在实验室条件下，VIR-O 和 AV-T 变体之间以高频率相互转换，表明表型转换背后的遗传机制可以被操纵以减弱毒力。因此，我们的小组专注于鉴定和表征调节这种转换的基因，这导致了对（）的研究，这是一个高度保守的基因，预测编码 LysR 型转录调节剂。ABUW_1132 被证明是一个全局调节剂，因为在一个 缺失突变体中，有 74 个基因的表达改变了≥2 倍。该缺失还导致 VIR-O 到 AV-T 转换减少了 16 倍，3-OH-C-HSL 分泌减少，表面相关运动减少。此外，在 AV-T 背景下缺失 导致荚膜产量增加，这增加了菌落不透明度，并改变了透明细胞的典型无毒表型。这些发现将 区分作为一个全局调节基因，并推进了我们对 的不透明度-毒力转换的理解。
