Identification of a capsular variant and characterization of capsular acetylation in Klebsiella pneumoniae PLA-associated type K57.
Identification of a capsular variant and characterization of capsular acetylation in Klebsiella pneumoniae PLA-associated type K57.
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DOI：
10.1038/srep31946
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发表时间：
2016-08-23
影响因子：
4.6
通讯作者：
Wang JT
中科院分区：
文献类型：
--
作者：
Hsu CR;Liao CH;Lin TL;Yang HR;Yang FL;Hsieh PF;Wu SH;Wang JT
肺炎克雷伯菌可引起社区获得性化脓性肝脓肿。荚膜多糖（CPS）具有重要的毒力。在迄今发现的79种荚膜(K)类型中，K57常与PLA相关。在这里，我们报告了K57变体的识别。Cps基因座测序显示K57参考菌株4425/51 （Ref-K57）与PLA变体A1142之间存在差异。虽然Ref-K57 cps含有orf13编码一个假定的乙酰转移酶，但在A1142中检测到在该位置插入一个假定的转座酶编码基因。在其他K57临床菌株中也发现了这种变异。生化分析表明A1142缺乏CPS乙酰化。遗传替换和互补证实orf13是CPS乙酰化的主要原因。乙酰化增加了CPS对抗血清的免疫反应性，并通过JNK和MAPK信号传导增强了肺炎克雷伯菌对促炎细胞因子的诱导。虽然乙酰化降低了细菌的血清抗性，但它促进了肠上皮细胞的粘附，可能是通过增加I型菌毛的产生。总之，观察到乙酰化介导的K57荚膜变异。荚膜乙酰化有助于CPS的多样性和抗原多样性，影响其生物活性，并参与肺炎克雷伯菌与宿主的相互作用。这些发现对肺炎克雷伯菌的疫苗设计和致病性具有指导意义。
Klebsiella pneumoniae can cause community-acquired pyogenic liver abscess (PLA). Capsular polysaccharide (CPS) is important for its virulence. Among 79 capsular (K) types discovered thus far, K57 is often associated with PLA. Here, we report the identification of a K57 variant. Cps gene locus sequencing revealed differences between the K57 reference strain 4425/51 (Ref-K57) and a variant, the PLA isolate A1142. While Ref-K57 cps contained orf13 encoding a putative acetyltransferase, the insertion of a putative transposase-encoding gene at this position was detected in A1142. This variation was detected in other K57 clinical strains. Biochemical analyses indicated that A1142 was deficient in CPS acetylation. Genetic replacement and complementation verified that orf13 was responsible for CPS acetylation. Acetylation increased CPS immunoreactivity to antiserum and enhanced K. pneumoniae induction of pro-inflammatory cytokines through JNK and MAPK signaling. While acetylation diminished the serum resistance of bacteria, it promoted adhesion to intestinal epithelial cells possibly via increasing production of type I fimbriae. In conclusion, acetylation-mediated capsular variation in K57 was observed. Capsular acetylation contributed to the variety and antigenic diversity of CPS, influenced its biological activities, and was involved in K. pneumoniae-host interactions. These findings have implications for vaccine design and pathogenicity of K. pneumoniae.