The role of Klebsiella pneumoniae rmpA in capsular polysaccharide synthesis and virulence revisited

The role of Klebsiella pneumoniae rmpA in capsular polysaccharide synthesis and virulence revisited
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DOI:
10.1099/mic.0.050336-0
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发表时间:
2011-12-01
期刊:
影响因子:
2.8
通讯作者:
Wang, Jin-Town
Wang, Jin-Town
中科院分区:
生物学4区
文献类型:
--
作者:
Hsu, Chun-Ru;Lin, Tzu-Lung;Wang, Jin-Town

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肺炎克雷伯菌社区获得性化脓性肝脓肿是一种新发传染病。据报道,rmpA基因(粘液表型A的调节因子)与流行研究中的PLA相关。NTUH-K2044是一个K1 PLA分离物,携带三个rmpA/A2基因:两个大质粒携带基因(p-rmpA和p-rmpA 2)和一个染色体基因(c-rmpA)。在这项研究中,我们重新研究了rmpA/A2在PLA发病机制中的作用,以阐明rmpA/A2和荚膜血清型与毒力的关系。使用NTUH-K2044的同基因缺失菌株和互补菌株,我们证明了只有p-rmpA增强荚膜多糖合成(cps)基因的表达和荚膜产量。然而,致死剂量和体内竞争指数表明,p-rmpA不会促进小鼠的毒力。研究了206株菌株中这三种rmpA/A2和荚膜类型的患病率。这揭示了rmpA/A2与六种PLA相关的荚膜类型(K1、K2、K5、K54、K57和KN 1)的相关性。而rmpA/A2与西方K1株的相关性(17/22)低于亚洲K1株(39/39)(P=0.0019)。在3种rmpA/A2基因中,p-rmpA基因最为常见。由于与PLA相关的荚膜类型的强相关性,p-rmpA可以作为PLA的替代标记物。我们发现p-rmpA与一个大质粒中的三个间隔较宽的基因座相关(30/32)。因此,rmpA可能与该质粒携带的毒力基因共同遗传。
Klebsiella pneumoniae community-acquired pyogenic liver abscess (PLA) is an emerging infectious disease. The rmpA gene (for regulator of mucoid phenotype A) has been reported to be associated with PLA in prevalence studies. NTUH-K2044, a K1 PLA isolate, carries three rmpA/A2 genes: two large-plasmid-carried genes (p-rmpA and p-rmpA2) and one chromosomal gene (c-rmpA). In this study, we re-examined the role of rmpA/A2 in PLA pathogenesis to clarify the relationship of rmpA/A2 and capsular serotype to virulence. Using isogenic gene deletion strains and complemented strains of NTUH-K2044, we demonstrated that only p-rmpA enhanced expression of capsular polysaccharide synthesis (cps) genes and capsule production. Nevertheless, the lethal dose and in vivo competitive index indicated that p-rmpA does not promote virulence in mice. The prevalence of these three rmpA/A2 and capsular types in 206 strains was investigated. This revealed a correlation of rmpA/A2 with six PLA-related capsular types (K1, K2, K5, K54, K57 and KN1). However, the correlation of rmpA/A2 with K1 strains from the West was less obvious than with the strains from Asia (17/22 vs 39/39, P=0.0019). Among the three rmpA/A2 genes, p-rmpA was the most prevalent. Due to the strong correlation with PLA-related capsular types, p-rmpA could serve as a surrogate marker for PLA. We found an association of p-rmpA with three widely spaced loci in a large plasmid (30/32). Therefore, rmpA could be co-inherited together with virulence genes carried by this plasmid.