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1.
The multivalent pneumococcal conjugate vaccine is effective against both systemic disease and otitis media caused by serotypes contained in the vaccine. However, serotypes not covered by the present conjugate vaccine may still cause pneumococcal disease. To address these serotypes, and the remaining otitis media due to Streptococcus pneumoniae, efforts have been devoted to identifying protective protein antigens. Immunity to conserved surface proteins important for adhesion, nutrient acquisition, or other functions could result in a reduction of colonization and a lower disease potential. We have been searching for conserved surface-exposed proteins from S. pneumoniae that may be involved in pathogenesis to test as vaccine candidates. Here, an approximately 20-kDa protein that has significant homology to a nonheme iron-containing ferritin protein from Listeria innocua and other bactoferritins was identified as pneumococcal protective protein A (PppA). We expressed and purified recombinant PppA (rPppA) and evaluated its potential as a vaccine candidate. The antibodies elicited by purified rPppA were cross-reactive with PppA from multiple strains of S. pneumoniae and were directed against surface-exposed epitopes. Intranasal immunization of BALB/c mice with PppA protein and either a synthetic monophosphoryl lipid A analog, RC529AF, or a cholera toxin mutant, CT-E29H, used as an adjuvant reduced nasopharyngeal colonization in mice following intranasal challenge with a heterologous pneumococcal strain. PppA-specific systemic and local immunoglobulin G (IgG) and IgA antibody responses were induced. The antisera reacted with whole cells of a heterologous S. pneumoniae type 3 strain. These observations indicate that PppA may be a promising candidate for inclusion in a vaccine against pneumococcal otitis media.  相似文献   

2.
The multivalent pneumococcal conjugate vaccine is effective against both systemic disease and otitis media caused by serotypes contained in the vaccine. However, serotypes not covered by the current conjugate vaccine may still cause pneumococcal disease. To address these serotypes and the remaining otitis media due to Streptococcus pneumoniae, we have been evaluating antigenically conserved proteins from S. pneumoniae as vaccine candidates. A previous report identified a 20-kDa protein with putative human complement C3-proteolytic activity. By utilizing the publicly released pneumococcal genomic sequences, we found the gene encoding the 20-kDa protein to be part of a putative open reading frame of approximately 2,400 bp. We recombinantly expressed a 79-kDa fragment (rPhpA-79) that contains a repeated HxxHxH motif and evaluated it for vaccine potential. The antibodies elicited by the purified rPhpA-79 protein were cross-reactive to proteins from multiple strains of S. pneumoniae and were against surface-exposed epitopes. Immunization with rPhpA-79 protein adjuvanted with monophosphoryl lipid A (for subcutaneous immunization) or a mutant cholera toxin, CT-E29H (for intranasal immunization), protected CBA/N mice against death and bacteremia, as well as reduced nasopharyngeal colonization, following intranasal challenge with a heterologous pneumococcal strain. In contrast, immunization with the 20-kDa portion of the PhpA protein did not protect mice. These results suggest that rPhpA-79 is a potential candidate for use as a vaccine against pneumococcal systemic disease and otitis media.  相似文献   

3.
The rlrA pathogenicity islet in Streptococcus pneumoniae TIGR4 encodes three surface proteins, RrgA, RrgB, and RrgC, and three sortase enzymes. Using transmission electron microscopy, cell fractionation, cell wall sorting signal domain swapping, and Western blotting, we show that RrgA and RrgB are incorporated into a multisubunit pilus in S. pneumoniae.  相似文献   

4.
Gong Y  Xu W  Cui Y  Zhang X  Yao R  Li D  Wang H  He Y  Cao J  Yin Y 《Infection and immunity》2011,79(2):867-878
Zinc metalloprotease B (ZmpB) is present in all isolated pneumococcal strains and contributes to the pathogenesis of pneumococcal infection. In this study, recombinant ZmpB was cloned and expressed in Escherichia coli. The expression of ZmpB by different pneumococcal strains was detectable by Western blotting with antisera raised to recombinant ZmpB. Flow cytometry analysis demonstrated that anti-ZmpB polyclonal antibodies could bind to the cell surface of the pneumococcal strains analyzed. Both recombinant ZmpB protein and anti-ZmpB polyclonal antibodies significantly inhibited the adhesion of Streptococcus pneumoniae D39 to A549 cells. In mouse models, mucosal immunization with recombinant ZmpB could significantly reduce pneumococcal lung colonization caused by S. pneumoniae serotypes 19F and 14 and significantly increase mice survival times following invasive pneumococcal challenge with different pneumococcal strains, including serotypes 2, 3, 6B, and 14. Furthermore, intraperitoneal immunization with recombinant ZmpB in combination with the recombinant pneumolysin mutant (DeltaA146 Ply) and heat shock protein 40 (DnaJ) could enhance the protection against pneumococcal infection compared to protection provided by single-protein antigens. Passive immunization with hyperimmune antisera against these three antigens also demonstrated that the combination of three hyperimmune antisera could provide better protection than single antisera. Taken together, our results suggest that ZmpB is a good candidate pneumococcal vaccine antigen.  相似文献   

5.
Streptococcus pneumoniae is an important pathogen accounting for a large number of deaths worldwide. Due to drawbacks of the current polysaccharide-based vaccine, the most promising way to generate an improved vaccine may be to utilize protection-eliciting pneumococcal proteins. Pneumococcal surface adhesin A (PsaA) and pneumococcal surface protein A (PspA) are two vaccine candidates which have been evaluated against S. pneumoniae infection in animal models or human clinical trials with encouraging results. In this study, the efficacy of the fusion protein PsaA–PspA, which includes PsaA part and PspA part, in inducing immunoprotective effects against fatal pneumococcal challenge was evaluated in an animal model. PspA part of PsaA–PspA fusion protein contains both family1 N-terminal region and family 2 N-terminal clade-defining region of PspA. Immunization with the PsaA–PspA fusion protein induced high levels of antibodies against both PsaA and PspA, which could bind to intact S. pneumoniae strains bearing different PspAs. Ex vivo stimulation of splenocytes from mice immunized with PsaA–PspA induced IL-17A secretion. Mice immunized with PsaA–PspA showed reduced S. pneumoniae levels in the blood and lungs compared with the PBS group after intranasal infection. Finally, mice immunized with PsaA–PspA fusion proteins were protected against fatal challenge with pneumococcal strains expressing different PspAs regardless of the challenge route. These results support the PsaA–PspA fusion protein as a promising vaccine strategy, as demonstrated by its ability to enhance the immune response and stimulate production of high titer antibodies against S. pneumoniae strains bearing heterologous PspAs, as well as confer protection against fatal challenge with PspA family 1 and family 2 strains.  相似文献   

6.
目的 比较肺炎链球菌(Streptococcus pneumoniae)表面黏附素A(PsaA)和表面蛋白A(PspA)的免疫原性.方法 电泳分析Sp6B亚型菌株的两种外膜蛋白基因及所编码蛋白相对分子质量的可变性,采用Western blot方法比较两种重组外膜蛋白对5种亚型菌株相应蛋白抗血清的交叉反应,采用酶联免疫吸附法(ELISA)分析两种外膜蛋白的抗体类型和抗体水平以及抗血清对5种亚型菌株的亲和性,以小鼠保护实验比较两种蛋白对5种亚型菌株的交叉保护作用.结果 两种蛋白产生的抗体亚型水平相当;PspA蛋白与其他亚型蛋白的交叉反应广泛性不如PsaA蛋白,只限于同一支系的蛋白之间;PspA抗体与病原菌具有可接近性,并具备交叉免疫保护作用.可作为一种更有效的抗原成分.结论 PspA对同家族同支系菌株攻击具有交叉免疫保护作用,可作为一种更有效的抗原成分.  相似文献   

7.
One of the candidate proteins for a mucosal vaccine antigen against Streptococcus pneumoniae is PsaA (pneumococcal surface antigen A). Vaccines targeting mucosal immunity may raise concerns as to possible alterations in the normal microbiota, especially in the case of PsaA, which was shown to have homologs with elevated sequence identity in other viridans group streptococci. In this work, we demonstrate that intranasal immunization with a cholera toxin B subunit-PsaA fusion protein is able to protect mice against colonization with S. pneumoniae but does not significantly alter the natural oral or nasopharyngeal microbiota of mice.  相似文献   

8.
For most bacteria, adherence to human cells is achieved by bacterial lectins binding to mammalian surface glyconjugates. 6-Phosphogluconate dehydrogenase (6PGD) was identified by us as one of Streptococcus pneumoniae cell wall lectin proteins, which elicits an age-dependent immune response in humans. This study assesses the role of 6PGD in S. pneumoniae pathogenesis as an adhesin and its ability to elicit a protective immune response in mice. Recombinant 6PGD (r6PGD) was cloned from S. pneumoniae serotype 3 (strain WU2). r6PGD interference in adhesion of three genetically unrelated unencapsulated pneumococcal strains (3.8, 14.8 and R6) and two genetically unrelated encapsulated pneumococcal strains (WU2 and D39) to A549 type II lung carcinoma cell was tested. BALB/c mice were immunized with r6PGD and boosted after 3 weeks. Immunized mice were challenged intranasally with a lethal dose of S. pneumoniae. r6PGD inhibited 90% and 80% of pneumococcal adhesion to the A549 cells of three unencapsulated S. pneumoniae strains and two encapsulated S. pneumoniae strains, respectively, in a concentration-dependent manner (P < 0.05). Antibodies to r6PGD produced in mice significantly inhibited bacterial adhesion to A549 cell (P < 0.05). Immunization of mice with r6PGD protected 60% (P < 0.001) of mice for 5 days and 40% (P < 0.05) of the mice for 21 days following intranasal lethal challenge. We have identified 6PGD as a surface-located immunogenic lectin protein capable of acting as an adhesin. 6PGD importance to bacterial pathogenesis was demonstrated by the ability of r6PGD to elicit a protective immune response in mice.  相似文献   

9.
Antibodies to capsular polysaccharide (PS) are protective against systemic infection by Streptococcus pneumoniae, but the large number of pneumococcal serogroups and the age-related immunogenicity of pure PS limit the utility of PS-based vaccines. In contrast, cell wall-associated proteins from different capsular serotypes can be cross-reactive and immunogenic in all age groups. Therefore, we evaluated three pneumococcal proteins with respect to relative accessibility to antibody, in the context of intact pneumococci, and their ability to elicit protection against systemic infection by encapsulated S. pneumoniae. Sequences encoding pneumococcal surface adhesin A (PsaA), putative protease maturation protein A (PpmA), and the N-terminal region of pneumococcal surface protein A (PspA) from S. pneumoniae strain A66.1 were cloned and expressed in Escherichia coli. The presence of genes encoding PsaA, PpmA, and PspA in 11 clinical isolates was examined by PCR, and the expression of these proteins by each strain was examined by Western blotting with antisera raised to the respective recombinant proteins. We used flow cytometry to demonstrate that PspA was readily detectable on the surface of the pneumococcal strains analyzed, whereas PsaA and PpmA were not. Consistent with these observations, mice with passively or actively acquired antibodies to PspA or type 3 PS were equivalently protected from homologous systemic challenge with type 3 pneumococci, whereas mice with passively or actively acquired antibodies to PsaA or PpmA were not effectively protected. These experiments support the hypothesis that the extent of protection against systemic pneumococcal infection is influenced by target antigen accessibility to circulating host antibodies.  相似文献   

10.
Streptococcus pneumoniae is a problematic infectious agent, whose seriousness to human health has been underscored by the recent rise in the frequency of isolation of multidrug-resistant strains. Pneumococcal pneumonia in the elderly is common and often fatal. Young children in the developing world are at significant risk for fatal pneumococcal respiratory disease, while in the developed world otitis media in children results in substantial economic costs. Immunocompromised patients are extremely susceptible to pneumococcal infection. With 90 different capsular types thus far described, the diversity of pneumococci contributes to the challenges of preventing and treating S. pneumoniae infections. The current capsular polysaccharide vaccine is not recommended for use in children younger than 2 years and is not fully effective in the elderly. Therefore, innovative vaccine strategies to protect against this agent are needed. Given the immunogenic nature of S. pneumoniae proteins, these molecules are being investigated as potential vaccine candidates. Pneumococcal surface protein A (PspA) has been evaluated for its ability to elicit protection against S. pneumoniae infection in mouse models of systemic and local disease. This review focuses on immune system responsiveness to PspA and the ability of PspA to elicit cross-protection against heterologous strains. These parameters will be critical to the design of broadly protective pneumococcal vaccines.  相似文献   

11.
Streptococcus pneumoniae is the most common cause of community-acquired pneumonia in the United States and globally. Despite the availability of pneumococcal capsular polysaccharide (PPS) and protein conjugate-based vaccines, the prevalence of antibiotic-resistant pneumococcal strains, serotype (ST) replacement in nonconjugate vaccine strains, and uncertainty as to whether the PPS vaccine that is used in adults protects against pneumonia emphasize the need for continued efforts to understand the nature of protective PPS antibody responses. In this study, we generated mouse monoclonal antibodies (MAbs) to a conjugate consisting of the PPS of serotype 8 (PPS8) S. pneumoniae and tetanus toxoid. Thirteen MAbs, including four IgMs that bound to PPS8 and phosphorylcholine (PC) and five IgMs and four IgG1s that bound to PPS8 but not PC, were produced, and their nucleotide sequences, epitope and fine specificity, and efficacy against lethal challenge with ST8 S. pneumoniae were determined. MAbs that bound to PPS8 exhibited gene use that was distinct from that exhibited by MAbs that bound to PC. Only PPS8-binding MAbs that did not bind PC were protective in mice. All 13 MAbs used germ line variable-region heavy (V(H)) and light (V(L)) chain genes, with no evidence of somatic hypermutation. Our data reveal a relationship between PPS specificity and V(H) gene use and MAb efficacy in mice. These findings provide insight into the relationship between antibody molecular structure and function and hold promise for the development of novel surrogates for pneumococcal vaccine efficacy.  相似文献   

12.
Streptococcus pneumoniae is an important human pathogen causing both mucosal (otitis media and pneumonia) and systemic (sepsis and meningitis) diseases. Due to increasing rates of antibiotic resistance, there is an urgent need to improve prevention of pneumococcal disease. Two currently licensed vaccines have been successful in reducing pneumococcal disease, but there are limitations with their use and effectiveness. Another approach for prevention is the use of live attenuated vaccines. Here we investigate the safety and protection induced by live attenuated strains of S. pneumoniae containing combinations of deletions in genes encoding three of its major virulence determinants: capsular polysaccharide (cps), pneumolysin (ply), and pneumococcal surface protein A (pspA). Both the cps and ply/pspA mutants of a virulent type 6A isolate were significantly attenuated in a mouse model of sepsis. These attenuated strains retained the ability to colonize the upper respiratory tract. A single intranasal administration of live attenuated vaccine without adjuvant was sufficient to induce both systemic and mucosal protection from challenge with a high dose of the parent strain. Immunization with cps mutants demonstrated cross-protective immunity following challenge with a distantly related isolate. Serum and mucosal antibody titers were significantly increased in mice immunized with the vaccine strains, and this antibody is required for full protection, as microMT mice, which do not make functional, specific antibody, were not protected by immunization with vaccine strains. Thus, colonization by live attenuated S. pneumoniae is a potentially safe and less complex vaccine strategy that may offer broad protection.  相似文献   

13.
The vaccine potential of a combination of three pneumococcal virulence proteins was evaluated in an active-immunization-intraperitoneal-challenge model in BALB/c mice, using very high challenge doses of Streptococcus pneumoniae. The proteins evaluated were a genetic toxoid derivative of pneumolysin (PdB), pneumococcal surface protein A (PspA), and a 37-kDa metal-binding lipoprotein referred to as PsaA. Mice immunized with individual proteins or combinations thereof were challenged with high doses of virulent type 2 or type 4 pneumococci. The median survival times for mice immunized with combinations of proteins, particularly PdB and PspA, were significantly longer than those for mice immunized with any of the antigens alone. A similar effect was seen in a passive protection model. Thus, combinations of pneumococcal proteins may provide the best non-serotype-dependent protection against S. pneumoniae.  相似文献   

14.
Changes in the epidemiology of Streptococcus pneumoniae were reported worldwide after the introduction of the 7-valent pneumococcal vaccine, particularly an increase in multi-drug resistant (MDR) 19A strains. Subsequently, a 13-valent pneumococcal vaccine (PCV-13) has been introduced. This study assessed the incidence of S. pneumoniae serotypes in all age groups prior to the introduction of PCV-13 in Canada (2007-2009). Eight hundred S. pneumoniae isolates from respiratory specimens and blood cultures were collected as part of a Canadian surveillance study (CANWARD) from patients in 15 tertiary-care centers. Serotyping was performed by the Quellung method and antimicrobial susceptibility testing was performed by broth microdilution in accordance with the Clinical and Laboratory Standards Institute guidelines. The most common serotypes were 19A (8.6%), 3 (7.3%), 22F (6.0%), 4 (4.6%), 5 (4.4%), and 11A (4.4%); and the first serotype 6D isolate in Canada was identified. Serotypes 5, 7F, and 19A were significantly (p<0.001) more frequently isolated from bloodstream infections. Considerable serotype variability was noted for different age groups: 15B (p<0.01) and 19A (p<0.001) were more frequently isolated from children ≤2 years old. Overall, 46.4% of currently circulating S. pneumoniae serotypes in Canada are included in PCV-13. Notably, 87.5% of MDR-S. pneumoniae were covered by PCV-13. Accordingly, PCV-13 will provide coverage against a significant proportion of circulating S. pneumoniae strains in Canada, including the critical antimicrobial-resistant strains.  相似文献   

15.
D M Musher  B Johnson  Jr    D A Watson 《Infection and immunity》1990,58(12):3871-3876
We have recently shown that a substantial proportion of antibody to pneumococcal polysaccharide as measured by enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay is removed by adsorption with pneumococcal cell wall polysaccharide (CWPS). The present study was undertaken to validate the hypothesis that only serotype-specific antibody that remains after adsorption with CWPS provides protection against pneumococcal infection. Serum samples were obtained from human subjects before and after they had been vaccinated with pneumococcal polysaccharide vaccine. Antibody to Streptococcus pneumoniae serotype 4 was measured by ELISA without adsorption or after adsorption of serum with CWPS. Groups of mice were injected with graded doses of serum and then challenged intraperitoneally with 10, 100, or 1,000 50% lethal doses (LD50) of S. pneumoniae serotype 4. Without adsorption, prevaccination sera from five healthy adults appeared to contain up to 33 micrograms of antibody to S. pneumoniae serotype 4 antigen per ml; adsorption with CWPS removed all detectable antibody, and pretreating mice with up to 0.1 ml of these sera (less than or equal to 3.3 micrograms of antibody) failed to protect them against challenge with 100 LD50. In contrast, postvaccination sera contained 2.9 to 30 micrograms of antibody per ml that was not removed by adsorption. Diluting sera to administer desired amounts of serotype-specific immunoglobulin G showed a significant relationship between protection and antibody remaining after adsorption (P less than 0.05 by linear regression analysis); 150 ng was uniformly protective against 1,000 LD50, and 50 ng was protective against 100 LD50. These studies have, for the first time, quantitated the amount of serotype-specific antibody that protects mice against challenge with S. pneumoniae type 4. In light of these observations, it is necessary to reassess current concepts regarding the presence of antipneumococcal antibody in the unvaccinated population, responses to pneumococcal vaccination, and protective levels of immunoglobulin G.  相似文献   

16.
Streptococcus pneumoniae is an important pathogen accounting for a large number of deaths worldwide. Despite the multitude of capsular polysaccharide vaccines used to guard against pneumococcal disease, fatal pneumococcal disease remains epidemic due to the narrow range of protection afforded by the capsular polysaccharide vaccines and rate of change in serotypes. The most promising solution is to develop an improved protein-based vaccine with broad protection. In this study, we tested a bivalent vaccine containing antigens mixed with the fusion protein PsaA-pneumococcal surface protein A (PspA)23 and single protein PspA4, including conserved PsaA and PspA from clades 2, 3, and 4 with coverage for families 1 and 2. The vaccine induced a significant increase of anti-PspA IgG, which demonstrated cross-reactivity with the 22 different S. pneumoniae strains from serotypes contained in PPV23 by Western blot. The wide ranging protection was determined by challenging mice with S. pneumoniae from PspA clades 1 to 5. Bacterial loads in the blood and lung and survival rate after challenge were measured. After immunization, the number of bacteria in mice was significantly reduced. The clearance rates with all strains were greater than 90% in the lung, and bacterial loads in the blood were decreased to lower than 10 CFU/ml. The survival rates in immunized animals also were greatly increased (all over 50%) compared with controls. Therefore, this bivalent PspA vaccine may be a good substitute for capsular polysaccharide vaccines.  相似文献   

17.
Streptococcus pneumoniae is a leading cause of otitis media, sinusitis, pneumonia, bacteraemia and meningitis worldwide. The drawbacks associated with the limited number of various capsular polysaccharides that can be included in the polysaccharide-based vaccines focuses much attention on pneumococcal proteins as vaccine candidates. We extracted an enriched cell wall fraction from S. pneumoniae WU2. Approximately 150 soluble proteins could be identified by 2D gel electrophoresis. The proteins were screened by 2D-Western blotting using sera that were obtained longitudinally from children attending day-care centres at 18, 30 and 42 months of age and sera from healthy adult volunteers. The proteins were further identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry. Seventeen proteins were antigenic in children and adults, of which 13 showed an increasing antibody response with age in all eight children analysed. Two immunogenic proteins, fructose-bisphosphate aldolase (FBA) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and a control protein with known low immunogenicity, heat shock protein 70 (DnaK), were expressed in Escherichia coli, purified and used to immunize mice. Mouse antibodies elicited to the recombinant (r) FBA and rGAPDH were cross-reactive with several genetically unrelated strains of different serotypes and conferred protection to respiratory challenge with virulent pneumococci. In addition, the FBA used in this study (NP_345117) does not have a human ortholog and warrants further investigation as a candidate for a pneumococcal vaccine. In conclusion, the immunoproteomics based approach utilized in the present study appears to be a suitable tool for identification of novel S. pneumoniae vaccine candidates.  相似文献   

18.
Nasopharyngeal carriage is a major factor in the transmission of pneumococcal disease. The aim of this study was to determine the prevalence of asymptomatic nasopharyngeal carriage of Streptococcus pneumoniae and the distribution of serogroups and serotypes in children aged 3-36 months attending day care centres in Belgium. A single nasopharyngeal swab was cultured from 467 children attending 30 different day care centres between December 2000 and March 2001. S. pneumoniae isolates were serotyped and their antibiotic susceptibilities assessed by disk diffusion. The overall nasopharyngeal carriage rate for S. pneumoniae was 21% in the 467 children. None of the commonly accepted risk factors studied was associated significantly with carriage. Capsular serotypes isolated were 19F (27.3%), 6B (20.2%), 23F (19.2%), 19A (10.1%), 6A (7.1%), 14 (5.1%) and others (11.0%). Theoretical coverage by the seven-valent (serotypes 4, 6B, 9V, 14, 18C, 19F and 23F) pneumococcal conjugate vaccine was 73.7%. Fourteen (14.1%) of 99 strains were non-susceptible to penicillin, 48 (48.5%) to tetracycline and 61 (61.6%) to erythromycin. Theoretical coverage by the seven-valent pneumococcal conjugate vaccine was 93% for the penicillin-resistant serotypes, 69% for the tetracycline-resistant serotypes and 75% for the erythromycin-resistant serotypes. Use of the seven-valent pneumococcal conjugate vaccine could potentially reduce nasopharyngeal carriage of the antibiotic-resistant strains.  相似文献   

19.
The recent discovery of a mobile genetic element encoding a pilus-like structure in Streptococcus pneumoniae and the demonstration of a role for the pilus in virulence in mice have led to the proposal of the use of the pilus as a candidate pneumococcal vaccine. We examined the frequency of occurrence of the pneumococcal pilus, as determined by the presence of the rrgC gene, and analyzed its association with virulence, capsular serotypes, and multilocus sequence types in the American Indian pneumococcal collection and isolates of S. pneumoniae from blood cultures collected at Children's Hospital Boston. Overall, 21.4% of strains in the American Indian collection had the rrgC gene, but there was no difference between isolates obtained from the nasopharynx and those obtained from sterile sites (blood or cerebrospinal fluid). Vaccine-type strains were significantly more likely than non-vaccine-type strains to have this pilus gene (P < 0.001). Among isolates with identical multilocus sequence types, there was a high concordance (95%) between the multilocus sequence type and the presence or the absence of rrgC. Finally, in the era of the pneumococcal conjugate vaccine, the frequency of rrgC in isolates from Children's Hospital Boston has decreased significantly (42.8% before 2000 versus 21.3% after 2000; P = 0.019). Therefore, our data show that the pilus is present in a minority of strains and is associated with certain serotypes and that its frequency has been reduced by the conjugate pneumococcal vaccine.  相似文献   

20.
Antibacterial resistance in pneumococci is increasing worldwide, primarily against β -lactams and macrolides. Understanding the role played by molecular determinants of resistance, transformation and competence in the evolution of Streptococcus pneumoniae is important in addressing this trend. Data from the Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin (PROTEKT) study indicate that about 40% of pneumococci display multidrug-resistant phenotypes (resistance to three or more antibiotics), with highly variable prevalence rates observed in different countries. Alterations in the structure of six penicillin-binding proteins (PBPs) have been described in S. pneumoniae (1a, 1b, 2x, 2a, 2b and 3), enabling resistance to β -lactam antibiotics. Mechanisms conferring macrolide resistance include resistance mediated through the erm (B) gene, which results in macrolide–lincosamide–streptogramin B resistance, or through the mef (A) gene, which encodes an antibiotic efflux pump. Another variant, mef (E), is also expressed in S. pneumoniae ; both mef (A) and mef (E) variants are associated with strains belonging to serotype 14. In addition to the selection pressure resulting from misuse of antibiotics, widespread vaccination programmes may contribute to changing pneumococcal epidemiology. Since the introduction of the seven-valent pneumococcal conjugate vaccine (PCV7), the rate of invasive pneumococcal disease due to PCV7 serotypes has declined significantly in many countries, but some countries have reported an increase in non-PCV7 serotypes. This phenomenon, termed 'replacement', is associated with certain pneumococcal serotypes or clones (e.g. serotype 19A). Whether novel 'vaccine escape recombinant' pneumococcal strains are emerging or changes in distribution are part of a secular cycle remains to be determined.  相似文献   

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