Pathogenesis of pneumococcal infection

Gillespie, SH; Balakrishnan, Indran

doi:10.1099/0022-1317-49-12-1057

Cited by 61 publications

(46 citation statements)

References 49 publications

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“…The ST9 clone has also been identified as an important cause of meningitis throughout the United Kingdom (10,15,37), and this clone is now recognized as a cause of invasive disease in other countries (http://www.mlst.net). There are many virulence factors other than the capsule involved in the pathogenesis of pneumococcal infection (14), and there is evidence that particular strains of pneumococci have a predilection for blood and cerebrospinal fluid (16). Further characterization of invasive clones such as ST9 will help to explain this process and may in the future offer targets for treatment or prevention of invasive pneumococcal disease.…”

Section: Discussionmentioning

confidence: 99%

Molecular Epidemiology of Erythromycin Resistance in Streptococcus pneumoniae Isolates from Blood and Noninvasive Sites

et al. 2002

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Erythromycin-resistant isolates of Streptococcus pneumoniae from blood cultures and noninvasive sites were studied over a 3-year period. The prevalence of erythromycin resistance was 11.9% (19 of 160) in blood culture isolates but 4.2% (60 of 1,435) in noninvasive-site isolates. Sixty-two of the 79 resistant isolates were available for study. The M phenotype was responsible for 76% (47 of 62) of resistance, largely due to a serotype 14 clone, characterized by multilocus sequence typing as ST9, which accounted for 79% (37 of 47) of M phenotype resistance. The ST9 clone was 4.8 times more common in blood than in noninvasive sites. All M phenotype isolates were PCR positive for mef(A), but sequencing revealed that the ST9 clone possessed the mef(A) sequence commonly associated with Streptococcus pyogenes. All M phenotype isolates with this mef(A) sequence also had sequences consistent with the presence of the Tn1207.1 genetic element inserted in the celB gene. In contrast, isolates with the mef(E) sequence normally associated with S. pneumoniae contained sequences consistent with the presence of the mega insertion element. All MLS B isolates carried erm(B), and two isolates carried both erm(B) and mef(E). Fourteen of the 15 MLS B isolates were tetracycline resistant and contained tet(M). However, six M phenotype isolates of serotypes 19 (two isolates) and 23 (four isolates) were also tetracycline resistant and contained tet(M). MICs for isolates with the mef(A) sequence were significantly higher than MICs for isolates with the mef(E) sequence (P < 0.001). Thus, the ST9 clone of S. pneumoniae is a significant cause of invasive pneumococcal disease in northeast Scotland and is the single most important contributor to M phenotype erythromycin resistance.

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Section: Discussionmentioning

confidence: 99%

Molecular Epidemiology of Erythromycin Resistance in Streptococcus pneumoniae Isolates from Blood and Noninvasive Sites

et al. 2002

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“…Furthermore, bacterial pathogens display GAGs or GAG-like polysaccharide antigens on their surfaces, for example, group A streptococci possess an HA-rich capsule (32). Microorganisms also secret enzymes such as hyaluronidase to release GAGs from connective tissue (33,34). Although many infectious agents can cause inflammatory arthritis, the actual antigen behind autoimmunity may be GAGs.…”

Section: Discussionmentioning

confidence: 99%

Glycosaminoglycans are a potential cause of rheumatoid arthritis

Wang

Roehrl²

2002

Proc. Natl. Acad. Sci. U.S.A.

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Rheumatoid arthritis (RA) is a chronic, systemic, and inflammatory disease of connective tissue with unknown etiology. We investigated whether aberrant immune responses to glycosaminoglycans (GAGs), a major component of joint cartilage, joint fluid, and other soft connective tissue, causes this disease. Here we show that injection of GAGs such as hyaluronic acid, heparin, and chondroitin sulfates A, B, and C induce arthritis, tendosynovitis, dermatitis, and other pathological conditions in mice. We developed a technique by staining tissue specimens with fluorochrome-or biotin-labeled GAGs to visualize the direct binding between cells and GAGs. We discovered that inflammatory infiltrates from the affected tissue are dominated by a distinct phenotype of GAG-binding cells, a significant portion of which are CD4 ؉ T cells. GAG-binding cells seem to be expanded in bone marrow of GAG-immunized mice. Furthermore, we identified GAG-binding cells in inflamed synovial tissue of human patients with RA. Our findings suggest that carbohydrate self-antigenic GAGs provoke autoimmune dysfunctions that involve the expansion of GAG-binding cells which migrate to anatomical sites rich in GAGs. These GAG-binding cells might, in turn, promote the inflammation and pathology seen both in our murine model and in human RA.

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“…S. pneumoniae is a component of the normal flora of the nasopharynges of approximately 50% of all adults, where it coexists with other microflora in a nonpathogenic state. In immunocompromised people, the elderly, and young children, S. pneumoniae bacteria that initially colonize the nasopharynx may spread to distal sites, such as the inner ear, lower respiratory tract, or bloodstream, and cause diseases ranging from otitis media to pneumonia to meningitis (7,18). Factors that lead to its spread from the nasopharynx to other sites of infection are not understood.…”

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confidence: 99%

Transcriptional Regulation in the Streptococcus pneumoniae rlrA Pathogenicity Islet by RlrA

2003

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The proper temporal expression of virulence genes during infection is crucial to the infectious life cycle of microbial pathogens, particularly in pathogens that encounter a multitude of environments in eukaryotic hosts. Streptococcus pneumoniae normally colonizes the nasopharynges of healthy adults but can cause a range of diseases at a variety of host sites. Transcriptional regulators that are essential for full virulence of S. pneumoniae in different animal models have been identified. One such regulator, rlrA, is required for colonization of the nasopharynx and lung infection but is dispensable for systemic infection. Previous work has shown that rlrA lies in a 12-kb pathogenicity islet, divergently opposed to three putative sortase-anchored surface proteins and three sortase enzymes. In addition to rlrA, one of the putative surface proteins and one of the sortases have also been shown to be essential for lung infection. In this work, we demonstrate that RlrA is a positive regulator of all seven genes in the rlrA pathogenicity islet, with transcriptional activation occurring at four different promoters in the islet with AT-rich sequences. These promoters direct the expression of rlrA itself, the three sortases, rrgA, and rrgBC. These data are consistent with the model whereby the rlrA pathogenicity islet acts in an autonomous manner to alter the bacterial surface components that interact with the pulmonary and nasopharyngeal environments.

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Pathogenesis of pneumococcal infection

Cited by 61 publications

References 49 publications

Molecular Epidemiology of Erythromycin Resistance in Streptococcus pneumoniae Isolates from Blood and Noninvasive Sites

Molecular Epidemiology of Erythromycin Resistance in Streptococcus pneumoniae Isolates from Blood and Noninvasive Sites

Glycosaminoglycans are a potential cause of rheumatoid arthritis

Transcriptional Regulation in the Streptococcus pneumoniae rlrA Pathogenicity Islet by RlrA

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