Chiang Tsung-Ta, Yang Ya-Sung, Yeh Kuo-Ming, Chiu Sun-Kang, Wang Ning-Chi, Lin Te-Yu, Huang Li-Yueh, Chang Feng-Yee, Siu L K, Lin Jung-Chung, Chen Jiun-Han
Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Division of Clinical Research, National Health Research Institutes, Taipei, Taiwan.
J Microbiol Immunol Infect. 2016 Feb;49(1):83-90. doi: 10.1016/j.jmii.2015.08.011. Epub 2015 Sep 9.
BACKGROUND/PURPOSE: The emergence of Klebsiella pneumoniae carbapenemase (KPC)-producing strains is a challenge for clinicians. The characteristics and virulence of variants of KPC-producing K. pneumoniae isolates were evaluated.
Five clinical isolates-three KPC subtypes from Taiwan (KPC2-TW, KPC3-TW, and KPC17-TW) and two clinical strains from the United States (US; KPC2-US, KPC3-US)-were included. Virulent traits and capsular serotypes were analyzed by Polymerase Chain Reaction (PCR). Serum killing, neutrophil phagocytosis, and mice lethargy studies were performed to evaluate virulence.
Multilocus sequence typing (MLST) demonstrated that KPC2-TW and KPC17-TW belonged to sequence type (ST)11, and KPC2-US, KPC3-US, and KPC3-TW to ST258. KPC3-TW expressed capsular serotype K1, whereas the others were non-K1/K2/K5 isolates. MLST analysis indicated that ST11 strains were serum resistant, whereas ST258 isolates were serum sensitive. ST11 isolates exhibited significantly higher 15-minute phagocytic rates than ST258 isolates (70.28 ± 16.68% vs. 34.88 ± 10.52%, p < 0.001). The capsular serotype K1 strain was more resistant to neutrophil phagocytosis than non-K1/K2/K5 isolates (27.1 ± 10.23% vs. 54.46 ± 20.94%, p = 0.050). All KPC-producing strain variants from Taiwan and the US demonstrated less virulence in a mouse lethality study, where the LD50 ranged from approximately 10(6) colony-forming units (CFU) to >10(7) CFU. Immunological responses were not significantly correlated with KPC subtype; however, responses were associated with MLST and capsular serotype.
Production of KPC itself was not associated with increased virulence despite different variants of KPC. The ST11 KPC-producing strain was resistant to serum killing, whereas capsular ss K1 was associated with resistance to neutrophil phagocytosis.
背景/目的：产肺炎克雷伯菌碳青霉烯酶（KPC）菌株的出现给临床医生带来了挑战。本研究评估了产KPC的肺炎克雷伯菌分离株变体的特征和毒力。
纳入了5株临床分离株，其中3株来自台湾的KPC亚型（KPC2-TW、KPC3-TW和KPC17-TW）以及2株来自美国的临床菌株（KPC2-US、KPC3-US）。通过聚合酶链反应（PCR）分析毒力特征和荚膜血清型。进行血清杀菌、中性粒细胞吞噬和小鼠嗜睡研究以评估毒力。
多位点序列分型（MLST）表明，KPC2-TW和KPC17-TW属于序列型（ST）11，而KPC2-US、KPC3-US和KPC3-TW属于ST258。KPC3-TW表达荚膜血清型K1，而其他菌株为非K1/K2/K5分离株。MLST分析表明，ST11菌株对血清具有抗性，而ST258分离株对血清敏感。ST11分离株的15分钟吞噬率显著高于ST258分离株（70.28±16.68%对34.88±10.52%，p<0.001）。荚膜血清型K1菌株比非K1/K2/K5分离株对中性粒细胞吞噬更具抗性（27.1±10.23%对54.46±20.94%，p=0.050）。在小鼠致死性研究中，来自台湾和美国的所有产KPC菌株变体的毒力均较低，其中半数致死量（LD50）范围约为10⁶菌落形成单位（CFU）至>10⁷CFU。免疫反应与KPC亚型无显著相关性；然而，反应与MLST和荚膜血清型相关。
尽管KPC存在不同变体，但KPC本身的产生与毒力增加无关。产ST11 KPC的菌株对血清杀菌具有抗性，而荚膜血清型K1与对中性粒细胞吞噬的抗性相关。
