Wang Tsui-Chin, Lin Jung-Chung, Chang Jen-Chang, Hiaso Ya-Wen, Wang Ching-Hsun, Chiu Sheng-Kung, Fung Chang-Phone, Chang Feng-Yee, Siu L Kristopher
National Institute of Infectious Disease and Vaccinology, National Health Research Institute, Zhunan, Miaoli, Taiwan.
Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Gut Pathog. 2021 Jun 22;13(1):40. doi: 10.1186/s13099-021-00439-z.
Two different types of hypervirulent K. pneumoniae (HvKp), the MLST-11 and serotype K1/K2 strains, have been frequently described in recent studies. Although these two types of strains were described to be HvKp, their virulence was not compared. In this study, in vitro and in vivo approaches were used to assess differences in virulence.
A total of twenty-nine isolates, including 6 strains of each of serotype K1 and K2 isolates and 17 strains of ST11 isolates, were selected for this study. Phenotypic tests of virulence were performed by the string test and analysis of the virulent associated genes was detected by PCR. In vitro models of serum resistance and phagocytosis were used as the parameters to assess the virulence. In-frame deletion of virulence-associated genes was performed to study their contributions to virulence. The median lethal dose, i.e., the LD, in mice was determined following IP injection.
Although serotype K1 and K2 strains and ST11 isolates had similar virulence gene profiles, the ST11 isolates showed less serum and phagocytic resistance than the serotype K1/K2 isolates. The mouse lethality test revealed that all ST11 isolates were unable to cause lethality, even at > 10 CFU, while serotypes K1 and K2 showed an LD at ≤ 10 CFU. Aerobactin or capsule knockout mutants exhibited a lower LD than the parental strain, while capsule mutants showed a more significant decrease in LD.
Since there was a significant difference in virulence levels between the two types of HvKp when assessed in in vitro and in vivo models, it may be better to use the designation "HvKp" for some strains based on animal studies to avoid confusion. Virulence and non-virulence could be analysed in a relative manner, especially in comparison studies.
最近的研究中经常描述两种不同类型的高毒力肺炎克雷伯菌（HvKp），即多位点序列分型11型（MLST-11）和血清型K1/K2菌株。尽管这两种类型的菌株被描述为HvKp，但未对它们的毒力进行比较。在本研究中，采用体外和体内方法评估毒力差异。
本研究共选择了29株分离株，包括6株血清型K1分离株、6株血清型K2分离株和17株ST11分离株。通过拉丝试验进行毒力表型测试，并通过PCR检测毒力相关基因。使用血清抗性和吞噬作用的体外模型作为评估毒力的参数。对毒力相关基因进行框内缺失以研究它们对毒力的贡献。经腹腔注射后测定小鼠的半数致死剂量，即LD。
尽管血清型K1和K2菌株与ST11分离株具有相似的毒力基因谱，但ST11分离株的血清抗性和吞噬抗性低于血清型K1/K2分离株。小鼠致死性试验显示，所有ST11分离株即使在>10 CFU时也无法导致死亡，而血清型K1和K2在≤10 CFU时显示出LD。气杆菌素或荚膜敲除突变体的LD低于亲本菌株，而荚膜突变体的LD下降更为显著。
由于在体外和体内模型中评估时，两种类型的HvKp之间的毒力水平存在显著差异，基于动物研究，可能最好对某些菌株使用“HvKp”这一名称以避免混淆。毒力和无毒力可以相对地进行分析，尤其是在比较研究中。
