Dramatic decrease of Streptococcus pneumoniae infections in Marseille, 2003–2014
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Medical microbiology
Pneumococcal infections
Abstract Streptococcus pneumoniae (S. pneumoniae) is a significant Gram-positive opportunistic pathogen responsible for a variety of lethal infections. This bacterium accounts for more deaths from diseases than any other single pathogen worldwide. Distinctively, these symptoms arise despite effective antibiotic therapy. This study unveiled a novel mechanism of resistance to S. pneumoniae infection by targeting pneumolysin (PLY) and sortase A (Srt A), the key virulence factors of S. pneumoniae. Through protein phenotype assays, we found alnustone to be a potent drug that inhibits both PLY and Srt A. Using a PLY-mediated hemolysis assay, we found that albumin can effectively reduce Srt A peptidase activity by blocking PLY oligomerization, thereby directly inhibiting PLY-expressing cytolysis. Co-incubation of S. pneumoniae D39 Srt A with small-molecule inhibitors reduces cell wall-bound Nan A (pneumococcal-anchored surface protein Srt A), inhibits biofilm formation, and significantly reduces biomass. But more interestingly, the protective effect of invasive pneumococcal disease (IPD) on murine streptococcus pneumoniae was further demonstrated. Our study proposes a detailed bacteriostatic mechanism of pneumococcal and highlights the major translational potential of targeting circulating PLY and Srt A to protect against pneumococcal infections. Our results suggest that the antiviral strategy of directly targeting PLY and Srt A with alnustone is a promising treatment option for Streptococcus pneumoniae and that alnustone can be used as an effective inhibitor of PLY and Srt A.
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Streptococcus pneumoniae continues to be an important bacterial pathogen associated with invasive (e.g. bacteraemia) and non-invasive (e.g. community-acquired respiratory tract) infections worldwide. Surveillance studies conducted nationally and globally can assist in determining trends across geographical areas and allow comparisons between countries. SAVE is an ongoing, annual, national study focused on characterizing invasive isolates of S. pneumoniae obtained across Canada. This Supplement documents the initial 5 years of the SAVE study (2011-15) during which 6207 invasive isolates of S. pneumoniae were evaluated. The three manuscripts in this Supplement provide a comprehensive examination of the changing patterns of invasive S. pneumoniae obtained across Canada over a 5 year period. The data highlight the evolution of S. pneumoniae antimicrobial resistance and multidrug resistance, serotype distribution, genotypic relatedness and virulence under pressure by vaccination and antimicrobial usage. This allows both clinicians and researchers nationally and globally to view the current status of invasive pneumococcal infections in Canada.
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Medical microbiology
Pneumococcal infections
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Streptococcus pneumoniae cell wall and cytoplasmic proteins contribute directly to pathogenesis of pneumococcal infection. Protective effect of pneumococcal proteins such as pneumolysin (Ply), muramylamidase (LytA) and pneumococcal surface protein A (PspA). There is discussion in the literature about development of conjugared pneumococcal vaccines, which should include polysaccharides of invasive serotypes of pneumococci as well as protein antigens of this pathogen, for prevention of infections caused by S. pneumoniae. Researches suggest that such hybrid vaccines will be effective, first of all, for children 65 years old because immune response to polysaccharide vaccines either do not form at all or insufficient for prevention of pneumococcal infection.
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ABSTRACT The role of pneumococcal surface protein C (PspC; also called SpsA, CbpA, and Hic) in sepsis by Streptococcus pneumoniae was investigated in a murine infection model. The pspC gene was deleted in strains D39 (type 2) and A66 (type 3), and the mutants were tested by being injected intravenously into mice. The animals infected with the mutant strains showed a significant increase in survival, with the 50% lethal dose up to 250-fold higher than that for the wild type. Our findings indicate that PspC affords a decisive contribution to sepsis development.
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Streptococcus pneumoniae has demonstrated a remarkable ability to adapt during the conjugate vaccine era. The increasing incidence of serotype 35B disease and emergence of a multidrug-resistant clone reported in this issue of the Journal of Clinical Microbiology (L. Olarte et al., J Clin Microbiol 55:724-734, 2017, https://doi.org/10.1128/JCM.01778-16) underscore the limitations of pneumococcal vaccines that target the polysaccharide capsule.
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ABSTRACT In order to study the mucosal and serum antibody response to polysaccharide-encapsulated bacteria in mice, a preparation of heat-inactivated Streptococcus pneumoniae type 4 was administered, with and without cholera toxin, at various mucosal sites. It appeared that intranasal immunization of nonanesthesized animals was superior to either oral, gastric, or colonic-rectal antigen delivery with regard to the induction of serum immunoglobulin G (IgG) and IgA, as well as saliva IgA antibodies specific for pneumococci. The marked IgA antibody response in feces after intranasal, but not after oral or gastric, immunization is suggestive of a cellular link between the nasal induction site and the distant mucosal effector sites. Intranasal immunization also induced antibodies in serum and in mucosal secretions against type-specific capsular polysaccharide. IgA and IgG antibody levels in pulmonary lavage fluids correlated well with saliva IgA and serum IgG antibodies, respectively. Antibody determinations in pulmonary secretions may therefore be redundant in some cases, and the number of experimental animals may be reduced accordingly. After intraperitoneal challenge with type 4 pneumococci, mice immunized intranasally were protected against both systemic infection and death, even without the use of cholera toxin as a mucosal adjuvant. Thus, an efficient intranasal vaccine against invasive pneumococcal disease may be based on a very simple formulation with whole killed pneumococci.
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Streptococcus Pyogenes
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Pneumococci, or Streptococcus pneumoniae, are gram-positive, lancet-shaped diplococci but may also grow in short chains. The polysaccharide polymer that forms the outer capsule of S pneumoniae is chemically and antigenically unique and is crucial to virulence. There are at least 90 distinct serotypes. The capsule allows the bacteria to resist phagocytosis by leukocytes unless the organisms have been opsonized by antibody or serum complement components. Certain pneumococcal serotypes, such as the heavily encapsulated type 3 pneumococcus, are particularly virulent. In fact, only 23 serotypes account for 80% of bacteremic pneumococcal infections in the United States; capsular polysaccharides from these 23 serotypes are incorporated into the polyvalent polysaccharide pneumococcal vaccine (PPSV23), which has been available since 1983. This review covers the epidemiology and pathogenesis of pneumococcal infections, clinical pneumococcal infections, and prevention of pneumococcal infections. Adverse outcomes in pneumococcal pneumonia, antibiotic treatment for penicillin-resistant S pneumoniae, and Centers for Disease Control and Prevention child and adolescent immunization schedules are discussed. This review contains 1 figure, 6 tables, and 41 references. Key words: bacterial pneumonia, PCV13, penicillin-resistant Streptococcus pneumoniae, pneumococcal pneumonia, pneumococcus, PPSV23, pneumonia vaccine, Streptococcus pneumoniae
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Isolates of Streptococcus pneumoniae in cultures of blood from 258 adults seen in 10 Franklin County, Ohio, hospitals from 1991 and 1992 were serotyped. Most strains (230 [89.2%]) belonged to serotypes that are included in the current pneumococcal vaccine. An additional 16 isolates (6.2%) were immunologically related to strains with serotypes that are included in the vaccine. Only 12 isolates (4.6%) were not covered by the vaccine. The rate of mortality from pneumococcal bacteremia in adults remains high (20%). While recent studies have documented the efficacy of the pneumococcal vaccine for preventing pneumococcal bacteremia (56 to 70%), use of the pneumococcal vaccine in susceptible patients by physicians remains low (19% in Franklin County). Additional efforts need to be expended to increase the use of the pneumococcal vaccine.
Bacteremia
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Pneumococcal infections
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