Molecular Microbial Pathogenesis Unit, Department of Cell Biology and Infection, Institut Pasteur, Paris, France.
INSERM U1202, Paris, France.
PLoS Negl Trop Dis. 2018 Jan 30;12(1):e0006201. doi: 10.1371/journal.pntd.0006201. eCollection 2018 Jan.
Rhinoscleroma is a human specific chronic granulomatous infection of the nose and upper airways caused by the Gram-negative bacterium Klebsiella pneumoniae subsp. rhinoscleromatis. Although considered a rare disease, it is endemic in low-income countries where hygienic conditions are poor. A hallmark of this pathology is the appearance of atypical foamy monocytes called Mikulicz cells. However, the pathogenesis of rhinoscleroma remains poorly investigated. Capsule polysaccharide (CPS) is a prominent virulence factor in bacteria. All K. rhinoscleromatis strains are of K3 serotype, suggesting that CPS can be an important driver of rhinoscleroma disease. In this study, we describe the creation of the first mutant of K. rhinoscleromatis, inactivated in its capsule export machinery. Using a murine model recapitulating the formation of Mikulicz cells in lungs, we observed that a K. rhinoscleromatis CPS mutant (KR cps-) is strongly attenuated and that mice infected with a high dose of KR cps- are still able to induce Mikulicz cells formation, unlike a K. pneumoniae capsule mutant, and to partially recapitulate the characteristic strong production of IL-10. Altogether, the results of this study show that CPS is a virulence factor of K. rhinoscleromatis not involved in the specific appearance of Mikulicz cells.
类鼻疽是一种由革兰氏阴性细菌鼻疽假单胞菌亚种引起的人类特有的慢性肉芽肿性鼻和上呼吸道感染。尽管被认为是一种罕见疾病,但在卫生条件较差的低收入国家,它是地方性的。这种病理学的一个标志是出现称为米库利茨细胞的非典型泡沫单核细胞。然而,类鼻疽的发病机制仍未得到充分研究。荚膜多糖 (CPS) 是细菌的一个重要毒力因子。所有鼻疽假单胞菌菌株均为 K3 血清型,表明 CPS 可能是类鼻疽疾病的重要驱动因素。在这项研究中,我们描述了创建第一个鼻疽假单胞菌突变体的过程,该突变体失活了其荚膜外排机制。使用一种模拟肺部米库利茨细胞形成的小鼠模型,我们观察到鼻疽假单胞菌 CPS 突变体 (KR cps-) 具有强烈的减毒作用,并且感染高剂量 KR cps-的小鼠仍能够诱导米库利茨细胞形成,这与肺炎克雷伯菌荚膜突变体不同,并且能够部分重现特征性的强烈 IL-10 产生。总之,这项研究的结果表明,CPS 是鼻疽假单胞菌的一种毒力因子,不参与米库利茨细胞的特异性出现。