Department of Life Sciences, National Chung-Hsing University, Taichung, Taiwan.
BMC Microbiol. 2011 Mar 8;11:50. doi: 10.1186/1471-2180-11-50.
Klebsiella pneumoniae displaying the hypermucoviscosity (HV) phenotype are considered more virulent than HV-negative strains. Nevertheless, the emergence of tissue-abscesses-associated HV-negative isolates motivated us to re-evaluate the role of HV-phenotype.
Instead of genetically manipulating the HV-phenotype of K. pneumoniae, we selected two clinically isolated K1 strains, 1112 (HV-positive) and 1084 (HV-negative), to avoid possible interference from defects in the capsule. These well-encapsulated strains with similar genetic backgrounds were used for comparative analysis of bacterial virulence in a pneumoniae or a liver abscess model generated in either naïve or diabetic mice. In the pneumonia model, the HV-positive strain 1112 proliferated to higher loads in the lungs and blood of naïve mice, but was less prone to disseminate into the blood of diabetic mice compared to the HV-negative strain 1084. In the liver abscess model, 1084 was as potent as 1112 in inducing liver abscesses in both the naïve and diabetic mice. The 1084-infected diabetic mice were more inclined to develop bacteremia and had a higher mortality rate than those infected by 1112. A mini-Tn5 mutant of 1112, isolated due to its loss of HV-phenotype, was avirulent to mice.
These results indicate that the HV-phenotype is required for the virulence of the clinically isolated HV-positive strain 1112. The superior ability of the HV-negative stain 1084 over 1112 to cause bacteremia in diabetic mice suggests that factors other than the HV phenotype were required for the systemic dissemination of K. pneumoniae in an immunocompromised setting.
与高黏液表型(HV)的肺炎克雷伯菌相比,HV 阴性菌株被认为具有更高的毒力。然而,组织脓肿相关的 HV 阴性分离株的出现促使我们重新评估 HV 表型的作用。
我们没有通过遗传手段操纵 HV 表型,而是选择了两种临床分离的 K1 株,1112(HV 阳性)和 1084(HV 阴性),以避免荚膜缺陷可能带来的干扰。这两种具有相似遗传背景的荚膜良好的菌株被用于在无菌或糖尿病小鼠中建立的肺炎或肝脓肿模型中比较细菌毒力。在肺炎模型中,HV 阳性株 1112 在无菌小鼠的肺部和血液中增殖到更高的负荷,但与 HV 阴性株 1084 相比,它不太容易扩散到糖尿病小鼠的血液中。在肝脓肿模型中,1084 在无菌和糖尿病小鼠中诱导肝脓肿的能力与 1112 相当。与感染 1112 的糖尿病小鼠相比,感染 1084 的糖尿病小鼠更倾向于发生菌血症,死亡率更高。由于失去 HV 表型而分离的 1112 的 mini-Tn5 突变体对小鼠没有毒力。
这些结果表明,HV 表型是临床分离的 HV 阳性株 1112 毒力所必需的。与 HV 阴性菌株 1084 相比,HV 阴性菌株 1084 更易在糖尿病小鼠中引起菌血症,这表明在免疫功能低下的情况下,HV 表型以外的因素可能是导致肺炎克雷伯菌全身传播的原因。