Klebsiella pneumoniae 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, rmpA, encodes a transcriptional regulator required for maximal capsule (cps) 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 cps regulator, RmpC, and ΔrmpC mutants have reduced cps 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 K. pneumoniae strains. Expression of rmpD in trans complements both ΔrmpD and ΔrmpA mutants for HMV, suggesting that RmpD is the key driver of this phenotype. The rmpD gene is located between rmpA and rmpC, 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 rmpD to produce HMV and rmpC to stimulate cps expression.

中文翻译：

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小蛋白RmpD驱动肺炎克雷伯菌中的黏液黏度增高。

肺炎克雷伯氏菌具有引起多种人类疾病的显着能力。它分为两大类：传统菌株，由于多药耐药性，在卫生保健机构中是一个显着的问题；和高毒力（hv）菌株，其历史上对药物敏感，但能够在有免疫能力的宿主中引起疾病​​。令人震惊的是，同时具有耐药性和与hv相关的基因的临床分离株的频率增加。一种这样的基因rmpA编码最大胶囊（cps）基因表达所需的转录调节子，并赋予黏膜黏膜黏度（HMV）。这种联系导致人们认为HMV是由胶囊产量增加引起的。然而，我们最近报道了新的CPS调节剂，RmpC和ΔrmpC突变体降低了cps表达，但保留了HMV，这表明胶囊生产和HMV可能是可分离的性状。在这里，我们报告鉴定出一种小蛋白RmpD，这对于HMV是必不可少的，但不会影响胶囊。RmpD是58个残基，带有一个假定的N端跨膜结构域和高度带正电的C端一半，在其他hv肺炎克雷伯菌菌株中均保守。表达RMPD在跨两个Δ互补RMPD和Δ RMPA突变体HMV，表明RMPD是这种表型的主要驱动力。该RMPD基因位于之间RMPA和rmpC，位于RmpA调控的操纵子中。这些数据与我们以前的工作相结合，提供一个模型，其中RMPA相关的表型，主要是由于RMPA激活的表达RMPD产生HMV和RMPC刺激厘泊的表达。