Streptococcus pneumoniae is a gram-positive bacterium that can be found in both healthy carriers as well as in people that have developed disease. One of the major virulence factors of pneumococci is their polysaccharide capsule. Based on the capsule that surrounds the bacteria, pneumococci are divided into at least 90 different serotypes. Some serotypes seem to be more related to virulence than others. I have with comparative genome hybridization microarray technique, studied gene differences between 18 epidemiological well-characterised pneumococcal strains with different potential to cause disease. A microarray chip based on two sequenced pneumococcal genomes, R6 and TIGR4, has already been designed. According to Hierarchical clustering, both the serotype and the genetic type as assessed by MLST (sequence type or ST) seem to have impact on the relationship of clinical isolates. Most clinical isolates of the same serotype are clustered together except for serotype 14 isolates that seem to be more divergent. Further more the number of genes that are divergent between clinical isolates compared to R6 and TIGR4 differ from 65 to 289. Preliminary results indicate that although there is diversity among clinical isolates some are more closely related to each other then others. Absent genes seem to be evenly distributed among all 18 clinical isolates tested but hypothetical genes and genes for cell envelope are two groups of role categories that are absent to the largest extent in all isolates. According to results from microarray analysis, a gene region, spr0112-spr1015- is present in all type 9V isolates and absent in many isolates of serotype 14, 19F and 7F. These results have been confirmed by polymerase chain reaction (PCR). Conserved genes in a region around the capsule genes have been sequenced to identify marker genes for a capsulular switch between serotype 9V and 14. Preliminary results of the sequencing showed that as much as 750kb might have been transferred in the event of capsular switch.

Bibliography: leaves 250-227. / 251 leaves : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The genetic loci encoding capsular polysaccharide synthesis have been characterized for all members of streptococcus pneumoniae serogroup. / Thesis (Ph.D.)--University of Adelaide, Dept. of Microbiology and Immunology, 1999?

Thesis (M. D.)--University of Hong Kong, 2008. / Includes bibliographical references (leaves 217-261) Also available in print.

Thesis (PhD)--Montana State University--Bozeman, 2009. / Typescript. Chairperson, Graduate Committee: Allen G. Harmsen. Includes bibliographical references (leaves 103-129).

Dissertação de Mestrado apresentada ao Programa de Pós Graduação em Ciências da Saúde, da universidade do Extremo Sul Catarinense – UNESC, para obtenção do título de Mestre em Ciências da Saúde. / Pneumococcal meningitis is a severe infectious disease of the central nervous system. This pathology is associated with acute inflammation and can cause damage to the host, such as deafness, blindness, seizure and learning deficits. Furthermore, infectious diseases can play a significant role in the etiology of neuro psychiatric disturbances. In this context, it was evaluated the depressive-like behavior in pneumococcal meningitis survivor rats. Wistar rats weighing 250-300g were underwent a magna cistern tap receiving either 10μL sterile saline or a Streptococcus pneumoniae suspension at the concentration 5×109 cfu/mL. After 3 days of the meningitis induction, the animals were treated with imipramine at 10 mg/kg or saline during 14 days (days 3-17). After 10 days of the induction of meningitis, it was measured the sweet food intake for 7 days (days 10-17). After 17 days of the induction, the animals were anesthetized and blood was removed for analysis of corticosterone and adrenocorticotropic hormone (ACTH). Adrenal gland and the hippocampus were isolated and weighed. The concentration of TNF-_ in the hippocampus and pre-frontal cortex was measured by the ELISA test. In the meningitis group, sucrose consumption was reduced in approximately 60% when compared to sham group. The treatment with imipramine reversed the reduction of sweet food intake in approximately 290% when compared to meningitis group. Regarding the weight of the adrenal gland and the hippocampus, it was any diference between meningitis and imipramine group. There was an increase in ACTH and corticosterone levels in the meningitis group compared to sham. In the meningitis group in comparison with the sham group, the levels of TNF-_ was increased in the pré-frontal cortex. In the hippocampus there was no changes in the TNF-_ levels. The treatment with imipramine decreased levels of ACTH and corticosterone in animals when compared with meningitis group. These results supported the hypothesis that survivor animals of the pneumococcal meningitis showed depressive-like behavior and alterations in the hypothalamus-pituitary-adrenal axis. / A meningite pneumocócica é uma doença grave que acomete o sistema nervoso central. Esta patologia está associada a uma inflamação aguda, que pode ocasionar danos ao hospedeiro, tais como surdez, cegueira, convulsões e prejuízos de memória e aprendizagem. Adicionalmente, as doenças infecciosas também podem desempenhar um papel importante em transtornos neuropsiquiátricos. Nesse contexto, foi avaliado o comportamento semelhante à depressão em ratos sobreviventes à meningite pneumocócica tratados com imipramina. Ratos Wistar, pesando entre 250-300g, foram submetidos à inoculação na cisterna magna com 10μL de solução salina estéril, ou um volume equivalente da suspensão de Streptococcus pneumoniae na concentração de 5x109 UFC/mL. Três dias após a indução da meningite, os animais foram tratados com imipramina 10mg/Kg ou com solução salina, durante 14 dias (3º ao 17º dia). Após dez dias da indução da meningite foi avaliado o consumo de alimento doce, durante 7 dias (10º ao 17º dia). Dezessete dias após a indução da meningite, os animais foram anestesiados e o sangue foi coletado para a análise dos níveis dos hormônios corticosterona e adrenocorticotrófico (ACTH). A glândula adrenal e o hipocampo foram isolados e pesados. A concentração de TNF-_ no hipocampo e no córtex pré-frontal foi determinada utilizando teste ELISA. No grupo meningite, o consumo de alimento doce foi reduzido em aproximadamente 60% quando comparado ao grupo controle. No entanto, o tratamento com imipramina no grupo meningite preveniu a redução do consumo de alimento doce em aproximadamente 290%, quando comparado com o grupo meningite. Em relação ao peso da glândula adrenal e do hipocampo, não houve diferença quando comparado ao grupo controle. Os níveis de corticosterona e ACTH estavam aumentados no grupo meningite quando comparados ao grupo controle. Já os níveis de TNF-_ estavam aumentados apenas no córtex pré-frontal dos animais. No hipocampo, os níveis de TNF-_ não foram alterados. Entretanto, o tratamento com a imipramina preveniu o aumento dos níveis de corticosterona e ACTH nos animais quando comparado com o grupo meningite. Assim, estes resultados corroboram a hipótese de que os animais sobreviventes à meningite pneumocócica apresentam comportamento semelhante à depressão e alterações no eixo hipotálamo-hipófise-adrenal.

Thesis (Masters Diploma(Technology))--Cape Technikon, Cape Town, 2000 / Streptococcus pneumoniae (S.pneumoniae) infections are an important cause of morbidity and mortality in adults and children worldwide. Mortality rates are highest amongst the very young and the elderly. Streptococcus pneumoniae is the most common form of community acquired bacterial pneumonia. Other diseases commonly caused by Streptococcus pneumoniae include meningitis, pericarditis, bacteraemia and septicaemia. Penicillin is today still consid3red the drug of choice when treating pneumococcal infections. The emergence of resistant pneumococcal strains has made it necessary to adapt antimicrobial regimens when treating pneumococcal infections. Hansman (1967) reported the first penicillin resistant strain, which was isolated from a woman in Australia in 1967. Since then penicillin and multi-resistant Streptococcus pneumoniae strains have been observed worldwide, including South Africa. Streptococcus pneumoniae infections may be caused by anyone of the 84 serotypes recognized to date. The distribution of serotypes varies, depending on geographical area, age and site of infection. High-level penicillin resistance and multiple resistant Streptococcus pneumoniae strains have been recognised worldwide in a few pneumococcal serotypes. Pneumococcal vaccines have been used since the seventies. These capsular polysaccharide vaccines are generally recommended for at risk population such as the elderly and immunocompromised patients. This vaccine is not effective in children under 2 years old. The current vaccine in South Africa (Pneumovax, MSD) consists of purified capsular polysaccharides of 23 pneumococcal serotypes. Conjugated polysaccharide vaccines have been developed to overcome the problems of efficacy in children < 2 years old. These vaccines consist of a capsular polysaccharide linked to a protein carrier, which makes them immunogenic in infants. Clinical trials of these vaccines are currently under way to demonstrate safety, efficacy and immunogenicity. Knowledge of serotype distribution and antimicrobial susceptibility patterns are important in relation to the treatment of pneumococcal diseases and vaccination programmes.

Streptococcus pneumoniae is a bacterium responsible for a spectrum of diseases including lobar pneumonia, meningitis, otitis media, and sinusitis. Invasive pneumococcal disease is responsible for significant morbidity and mortality across the world. Concerted efforts led to the development of two vaccinations, Pneumova × 23 and Prevnar 13, for the prevention of pneumococcal disease. The Advisory Committee on Immunization Practices of the US Centers for Disease Control and Prevention provides vaccination schedules for predisposed adults, but the proposed schedules remain a challenge to health-care providers. We performed a systematic review in PubMed and these specialty group websites to present the pathophysiology of pneumococcal disease, outline different pneumococcal vaccinations, and condense recommendations for vaccination administration.

Streptococcus pneumoniae is an asymptomatic colonizer of the upper respiratory tract as well as an opportunistic pathogen. Colonization is prerequisite to causing disease in a host, and it often involves formation of biofilms. There are currently two vaccines available against pneumococcus, both of which focus on preventing invasive disease by targeting the polysaccharide capsule of the most invasive serotypes. We hypothesized that by using membrane proteins expressed during the biofilm state, we can formulate an effective vaccine against colonization which would lead to an overall decrease in disease incidence. To do this, we selected protein candidates expressed during biofilm growth based on their ability to elicit an IgA response in human serum. Selected proteins (SP_0459, SP_1114, and SP_1702) were identified and used for further experiments. The proteins identified in this study will be paired with other immunogenic proteins to determine a successful vaccine formulation targeting colonization of Streptococcus pneumoniae.

Thesis (Ph. D.)--University of Alabama at Birmingham, 2008. / Title from first page of PDF file (viewed June 5, 2008). Includes bibliographical references.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences