Mechanism of respiratory infection due to H.influenae and protection gainst this infection

流感嗜血杆菌呼吸道感染的机制及预防措施

• 批准号: 08670321
• 负责人: MIYAZAKI Shuichi
• 金额: $ 1.34万
• 依托单位: Toho University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670321/
• 关键词: H.influenzae; CBO; murine model; virulence factors; evaluation of drugs; 莢膜b型; fimbriae; 評価; 気管支肺炎モデル

Haemophilus influenzae can cause a variety of both respiratory and systemic infections depending on the bacterial phenotype (encapsulated or unencapsulated). There is a possibility that oropharyngeal epithelial cells carrying cell-bound H.influenzae may exfoliate and enter the trachea, and produce infection in thelower respiratory tract. Accordingly, we have developed murine bronchopneumonia model with nontypable H.influenzae and sepsis/meningitis model with encapsulated (mainly type b) H.influenzae, using cell-bound organisms.In murine bronchopneumonia with -lactamase nonproducing and producing nontypable H.influenzae the efficacy of amoxicillin was obtained in the former model and that was not obtained in the latter model. This result indicates that we may be able to evaluate the in vivo activity of a drug in a new developed model.Furthermore, we studied the role of fimbriae on the pathogenesis of type bH.influenzae, using murine sepsis/meningitis. The mortality rate in fimbriated H.influenzae was higher than that in nonfimbriated H.influenzae. To the phagocytosis-killing activity of human sera, fimbriated H.influenzae organisms were more susceptible than nonfimbriated H.influenzae organisms. Moreover, the content of C3 bound to fimbriated organisms was more than to nonfimbriated organisms.

流感嗜血杆菌可引起多种呼吸道和全身感染，这取决于细菌表型（包囊或未包囊）。携带细胞结合流感嗜血杆菌的口咽上皮细胞可能脱落并进入气管，并在下呼吸道产生感染。因此，我们用细胞结合的微生物建立了不定型流感嗜血杆菌感染的小鼠支气管肺炎模型和包囊化（主要是B型）流感嗜血杆菌感染的脓毒症/脑膜炎模型，在不产生β-内酰胺酶和产生不定型流感嗜血杆菌感染的小鼠支气管肺炎模型中，阿莫西林的疗效在前一模型中得到，而在后一模型中没有得到。这一结果表明，我们可能能够在一个新开发的model. Further，我们研究了菌毛的作用对型bH.流感的发病机制，使用小鼠败血症/脑膜炎的体内活性的药物。菌毛型流感嗜血杆菌的死亡率高于非菌毛型流感嗜血杆菌。对人血清的吞噬杀伤活性，有菌毛的流感嗜血杆菌比无菌毛的流感嗜血杆菌更敏感。此外，与有菌毛生物结合的C3含量高于无菌毛生物。

项目成果

Miyazaki, S., Domon, H., Tateda, K., Ohono, A., Ishii, Y., Matsumoto, T., Furuya, N., Yamaguchi, K: "In vitroand in vivo antibacterial activities of CS-940, a new fluoroquinolone, against isolates from patients with respiratory infections." Antimicrob.Age

Miyazaki, S.、Domon, H.、Tateda, K.、Ohono, A.、Ishii, Y.、Matsumoto, T.、Furuya, N.、Yamaguchi, K：“CS-940 的体外和体内抗菌活性

Miyazaki S: "In vitio and in vivo autibacterial activity of CS-904 a new fluoro-auin lones against iselates frompatients with respiratory infections" Autimicrob Agents Chemolter. 41. 2582-2585 (1997)

Miyazaki S：“CS-904 的体外和体内自细菌活性，一种新型氟-auin 孤菌，可对抗呼吸道感染患者的孤立菌”Autimicrob Agents Chemolter。

Miyazaki, S., et al: "New murine model of bronchopneumouiae due to cell-bound Haemophilus influenzae" J.Infet.Dis. 175. 205-209 (1997)

Miyazaki, S. 等人：“由细胞结合的流感嗜血杆菌引起的支气管肺炎的新小鼠模型”J.Infet.Dis。

Miyazaki, S., et al.: "In vitro and in vivo autibacterial activity of CS-904,a new fluoroquinolones against isolates from patients with respiratary in fections" Autimicrob.Agents Chemother. 41. 2582-2583 (1997)

Miyazaki, S. 等人：“CS-904 的体外和体内自细菌活性，CS-904 是一种针对呼吸道感染患者分离株的新型氟喹诺酮类药物”Autimicrob.Agents Chemother。

Matsumoto, T., Tateda, K., Miyazaki, S., Furuya, N., Ohono, A., Ishii, Y., Hirakata, Y., Yamaguchi, K: "Immunonodulating effect of fosfomycin on gut-derived sepsis and Pseudomonas aeruginosa in mice." Antimicrob. Agents Chemother.41-2. 308-313 (1997)

Matsumoto, T.、Tateda, K.、Miyazaki, S.、Furuya, N.、Ohono, A.、Ishii, Y.、Hirakata, Y.、Yamaguchi, K.：“磷霉素对肠源性脓毒症的免疫调节作用