Hypermucoviscosity Regulator RmpD Interacts with Wzc and Controls Capsular Polysaccharide Chain Length.
Hypermucoviscosity Regulator RmpD Interacts with Wzc and Controls Capsular Polysaccharide Chain Length.
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肺炎克雷伯菌是医院感染的主要原因，包括肺炎、菌血症和尿路感染。治疗选择越来越受到包括碳青霉烯类在内的一线抗生素耐药性的高流行率以及最近发现的质粒赋予的粘菌素耐药性的限制。经典致病型(CKP)是全球观察到的大多数医院感染的原因，这些分离株往往是多重耐药的。超强毒力致病型(HvKp)是一种能够在免疫活性宿主中引起社区获得性感染的主要病原体。高粘液黏度(HMV)表型与hvKp分离株毒力增强密切相关。最近的研究表明，HMV需要胶囊(CPS)的合成和小蛋白RmpD的合成，但不依赖于与hvKp相关的胶囊数量的增加。在此，我们鉴定了含和不含RmpD的hvKp株KPPR1S(K2血清型)的囊外和胞外多糖的结构。我们发现，两个菌株的聚合物重复单元结构相同，并且与K2胶囊相同。然而，表达rmpD的菌株产生的CPS的链长更均匀。这一特性是从具有与肺炎克雷伯菌相同的CPS生物合成途径但天然缺乏rmpD的大肠杆菌分离株的CPS中重组的。此外，我们还证明了RmpD与Wzc结合，Wzc是CPS聚合和出口所需的一种保守的胶囊生物合成蛋白。基于这些观察，我们提出了一个RmpD与WZC相互作用如何影响CPS链长和HMV的模型。
Klebsiella pneumoniae is a leading cause of nosocomial infections, including pneumonia, bacteremia, and urinary tract infections. Treatment options are increasingly restricted by the high prevalence of resistance to frontline antibiotics, including carbapenems, and the recently identified plasmid-conferred colistin resistance. The classical pathotype (cKp) is responsible for most of the nosocomial infections observed globally, and these isolates are often multidrug resistant. The hypervirulent pathotype (hvKp) is a primary pathogen capable of causing community-acquired infections in immunocompetent hosts. The hypermucoviscosity (HMV) phenotype is strongly associated with the increased virulence of hvKp isolates. Recent studies demonstrated that HMV requires capsule (CPS) synthesis and the small protein RmpD but is not dependent on the increased amount of capsule associated with hvKp. Here, we identified the structure of the capsular and extracellular polysaccharide isolated from hvKp strain KPPR1S (serotype K2) with and without RmpD. We found that the polymer repeat unit structure is the same in both strains and that it is identical to the K2 capsule. However, the chain length of CPS produced by strains expressing rmpD demonstrates more uniform length. This property was reconstituted in CPS from Escherichia coli isolates that possess the same CPS biosynthesis pathway as K. pneumoniae but naturally lack rmpD. Furthermore, we demonstrate that RmpD binds Wzc, a conserved capsule biosynthesis protein required for CPS polymerization and export. Based on these observations, we present a model for how the interaction of RmpD with Wzc could impact CPS chain length and HMV.
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影响因子：
3.9
作者：
Follador R;Heinz E;Wyres KL;Ellington MJ;Kowarik M;Holt KE;Thomson NR
通讯作者：
Thomson NR
影响因子：
3.2
作者：
Ascari, Alice;Tran, Elizabeth Ngoc Hoa;Morona, Renato
通讯作者：
Morona, Renato
影响因子：
16.6
作者：
通讯作者：
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DOI：
10.1073/pnas.120163297
发表时间：
2000-06-06
影响因子：
11.1
作者：
Datsenko, KA;Wanner, BL
通讯作者：
Wanner, BL
影响因子：
5.7
作者：
Collins, Richard F.;Kargas, Vasileios;Ford, Robert C.
通讯作者：
Ford, Robert C.