2006 Fiscal Year Final Research Report Summary
Immunological and molecular-biological studies on pathogenesis and treatments of intractable obits media
| Project/Area Number |
17591797
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
YAMANAKA Noboru Wakayama Medical University, Otolaryngology, Professor, 医学部, 教授 (10136963)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIHARA Keiji Wakayama Medical University, Otolaryngology, Associate Professor, 医学部, 助教授 (80326371)
TAMURA Shinji Wakayama Medical University, Otolaryngology, Assistant Professor, 医学部, 講師 (10244724)
HOTOMI Muneki Wakayama Medical University, Otolaryngology, Assistant Professor, 医学部, 講師 (90336892)
YAMAUCHI Kazuma Wakayama Medical University, Otolaryngology, Instructor, 医学部, 助手 (80336891)
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| Project Period (FY) |
2005 – 2006
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| Keywords | otitis media / anti-microbial resistance / Streptococcus pneumoniae / Haemophilus influenzae / penicillin binding protein / genotype analysis / vaccine / maternal intranasal immunization |
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| Research Abstract |
S.pneumoniae and H.influenzae have been major pathogens in acute otitis media of children. Almost 75.8% strains had mutation in their penicillin binding protein la, 2b and 2x (PBP) and they were classified into seven genotypic classes after PCR identification of abnormal pbp1a, pbp2x, and pbp2b genes: (i) penicillin-susceptible S. pneumoniae (PSSP) isolates with no abnormal pbp genes (24.2%), (ii) genotypic penicillin-intermediate S. pneumoniae (gPISP) isolates with only an abnormal pbp2x gene [gPISP (2x)] (26%), (iii) with only an abnormal pbp1a gene [gPISP (/a)](0.1%) (iv) with only an abnormal pbp2b gene [gPISP (2b)](2.2%) (V) gPISP isolates with abnormal pbp1a and pbp2x genes (2.8%), (vi) gPISP isolates with abnormal pbp2x and pbp2b genes (2.2%), and (vii) genotypic penicillin-resistant S. pneumoniae (gPRSP) isolates with three abnormal pbp genes (38.5%). H. influenzae isolates were divided into 61.0% susceptible strains (MIC less than or equal 1 pg/ml), 37 (14.0%) intermediately r
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esistant strains (MIC =2 μg/ml) and 66 (25.0%) resistant strains (MIC greater than or equal 4 pg/ml). Five strains produced TEM type β-lactamase. They were divided into 3 (1.2%) strains with mutations in fts1 gene (gBLPACR: genetically β-lactamase producing amoxicillin-clavulanate resistant) and 2 (0.8%) strains without mutations infts1 gene gBLPAR (genetically β-lactamase producing ampicillin resistant). According to PCR-based genotyping, 172 (65.1%) isolates had mutations in fts1 gene without producing β-lactamase (gBLNAR: genetically β-lactamase nonproducing ampicillin resistant). They were 98 (37.1%) strains with group I/II mutations in variable mutated region (Group 1/II gBLNAR) and 74 (28.0%) strains with group III mutations in highly mutated region (Group III gBLNAR). The rest of 87 (33.0%) isolate were gBLNAS (genetically β-lactamase non-producing ampicillin susceptible) strains with neither mutations in fts1 gene nor bla gene. The Group III gBLNAR strains showed resistance to both penicillin and cephalosporin. PBP gene mutated H. influenzae not only resistance to ampicillin but also had reduce susceptibility to cephalosporin. The high prevalence of gBLNAR strains of H. influenzae should be taken into account when treating the upper respiratory tract infectious diseases.
It is very important to induce effective protective immunity among children younger than 2 years of age. In this study, we evaluated the maternal immunization of P6 of H.influenzae to evoke specific antibody to P6 and to transfer it to offspring. We intranasally immunized mother mice with P6 and investigated the induction of specific antibody in sera and breast milk. The specific antibody among offspring delivered from immunized mother was also investigated according to the nursing status to evaluate the importance of breast feedings by immunized mothers. Our findings strongly suggest that maternal intranasal immunization with P6 would be an attractive strategy against NTHi infections during early childhood. It can supply protective antibodies via transplacental during pregnancy and via breast milk after birth. Less
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