Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
mBio. 2020 Sep 22;11(5):e01750-20. doi: 10.1128/mBio.01750-20.
has a remarkable ability to cause a wide range of human diseases. It is divided into two broad classes: classical strains that are a notable problem in health care settings due to multidrug resistance, and hypervirulent (hv) strains that are historically drug sensitive but able to establish disease in immunocompetent hosts. Alarmingly, there has been an increased frequency of clinical isolates that have both drug resistance and hv-associated genes. One such gene, , encodes a transcriptional regulator required for maximal capsule () gene expression and confers hypermucoviscosity (HMV). This link has resulted in the assumption that HMV is caused by elevated capsule production. However, we recently reported a new regulator, RmpC, and Δ mutants have reduced expression but retain HMV, suggesting that capsule production and HMV may be separable traits. Here, we report the identification of a small protein, RmpD, that is essential for HMV but does not impact capsule. RmpD is 58 residues with a putative N-terminal transmembrane domain and highly positively charged C-terminal half, and it is conserved among other hv strains. Expression of in complements both Δ and Δ mutants for HMV, suggesting that RmpD is the key driver of this phenotype. The gene is located between and , within an operon regulated by RmpA. These data, combined with our previous work, suggest a model in which the RmpA-associated phenotypes are largely due to RmpA activating the expression of to produce HMV and to stimulate expression. Capsule is a critical virulence factor in , in both antibiotic-resistant classical strains and hypervirulent strains. Hypervirulent strains usually have a hypermucoviscosity (HMV) phenotype that contributes to their heightened virulence capacity, but the production of HMV is not understood. The transcriptional regulator RmpA is required for HMV and also activates capsule gene expression, leading to the assumption that HMV is caused by hyperproduction of capsule. We have identified a new gene () required for HMV but not for capsule production. This distinction between HMV and capsule production will promote a better understanding of the mechanisms of hypervirulence, which is in great need given the alarming increase in clinical isolates with both drug resistance and hypervirulence traits.
它具有引起广泛人类疾病的显著能力。它分为两类：经典菌株，由于多药耐药性，在医疗保健环境中是一个显著的问题；而高毒力（hv）菌株在历史上对药物敏感，但能够在免疫功能正常的宿主中引起疾病。令人震惊的是，临床分离株的药物耐药性和 hv 相关基因的频率都有所增加。其中一个基因 ，编码一个转录调节因子，该因子对于最大胶囊（ ）基因表达是必需的，并赋予超粘（HMV）。这一联系导致人们假设 HMV 是由胶囊产量增加引起的。然而，我们最近报道了一个新的 调节剂，RmpC，Δ 突变体的 表达减少，但保留 HMV，表明胶囊产生和 HMV 可能是可分离的特征。在这里，我们报告了一种小蛋白 RmpD 的鉴定，它对 HMV 是必需的，但不影响胶囊。RmpD 由 58 个残基组成，具有推定的 N 端跨膜结构域和高度正电荷的 C 端一半，并且在其他 hv 菌株中保守。在 中表达 可分别补充 Δ 和 Δ 突变体的 HMV，表明 RmpD 是该表型的关键驱动因素。 基因位于 和 之间，在由 RmpA 调节的操纵子中。这些数据，结合我们以前的工作，表明一个模型，即 RmpA 相关表型主要是由于 RmpA 激活 的表达产生 HMV 和 来刺激 的表达。在 中，无论是在具有抗生素耐药性的经典菌株还是高毒力菌株中，胶囊都是一种关键的毒力因子。高毒力菌株通常具有高粘滞性（HMV）表型，这有助于提高其毒力能力，但 HMV 的产生尚不清楚。转录调节因子 RmpA 是 HMV 所必需的，也激活了胶囊基因的表达，这导致了一个假设，即 HMV 是由胶囊的过度产生引起的。我们已经确定了一个新的基因（ ），它是 HMV 所必需的，但不是胶囊产生所必需的。这种 HMV 和胶囊产生之间的区别将促进对高毒力机制的更好理解，鉴于具有耐药性和高毒力特征的临床分离株的惊人增加，这是非常需要的。
