Manco Sonia, Hernon Fidelma, Yesilkaya Hasan, Paton James C, Andrew Peter W, Kadioglu Aras
Department of Infection, Immunity and Inflammation, University of Leicester, P.O. Box 138, University Rd., Leicester LE1 9HN, United Kingdom.
Infect Immun. 2006 Jul;74(7):4014-20. doi: 10.1128/IAI.01237-05.
We examined the role of the neuraminidases NanA and NanB in colonization and infection in the upper and lower respiratory tract by Streptococcus pneumoniae, as well as the role of these neuraminidases in the onset and development of septicemia following both intranasal and intravenous infection. We demonstrated for the first time using outbred MF1 mouse models of infection that both NanA and NanB were essential for the successful colonization and infection of the upper and lower respiratory tract, respectively, as well as pneumococcal survival in nonmucosal sites, such as the blood. Our studies have shown that in vivo a neuraminidase A mutant is cleared from the nasopharynx, trachea, and lungs within 12 h postinfection, while a neuraminidase B mutant persists but does not increase in either the nasopharynx, trachea, or lungs. We also demonstrated both neuraminidase mutants were unable to cause sepsis following intranasal infections. When administered intravenously, however, both mutants survived initially but were unable to persist in the blood beyond 48 h postinfection and were progressively cleared. The work presented here demonstrates the importance of pneumococcal neuraminidase A and for the first time neuraminidase B in the development of upper and lower respiratory tract infection and sepsis.
我们研究了肺炎链球菌的神经氨酸酶NanA和NanB在上、下呼吸道定植和感染中的作用,以及这些神经氨酸酶在鼻内和静脉感染后败血症的发生和发展中的作用。我们首次使用远交系MF1小鼠感染模型证明,NanA和NanB分别对上、下呼吸道的成功定植和感染以及肺炎链球菌在非粘膜部位(如血液)的存活至关重要。我们的研究表明,在体内,神经氨酸酶A突变体在感染后12小时内从鼻咽、气管和肺部清除,而神经氨酸酶B突变体持续存在,但在鼻咽、气管或肺部均未增加。我们还证明,两种神经氨酸酶突变体在鼻内感染后均无法引起败血症。然而,静脉注射时,两种突变体最初都能存活,但在感染后48小时内无法在血液中持续存在,并逐渐被清除。本文介绍的工作证明了肺炎链球菌神经氨酸酶A以及首次证明的神经氨酸酶B在上、下呼吸道感染和败血症发展中的重要性。