Serotype‐Related Differences in Inflammatory Response to<i>Streptococcus pneumoniae</i>in Experimental Meningitis

Engelhard, Dan; Pomeranz, Shlomo; Gallily, Ruth; Strauss, Nurith; Tuomanen, Elaine

doi:10.1086/514005

Cited by 47 publications

(38 citation statements)

References 14 publications

(7 reference statements)

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“…Mortality rates from invasive disease were increased with serotypes 3, 5, and 23, while infections with serotypes 1, 4, 6, 9V, 12F, and 14 were associated with lower mortality rates (3,31,34,46). Furthermore, during experimental pneumococcal meningitis serotypes 3 and 23 caused more severe inflammation than serotypes 1, 5, 9, and 7F (26,67). Interestingly, serotypes 3 and 23 were categorized here as group I biofilms and serotypes 6, 9, and 14 as group II biofilms ( Fig.…”

Section: Discussionmentioning

confidence: 94%

Phenotypic Characterization ofStreptococcus pneumoniaeBiofilm Development

et al. 2006

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Streptococcus pneumoniae is among the most common pathogens associated with chronic otitis media with effusion, which has been hypothesized to be a biofilm disease. S. pneumoniae has been shown to form biofilms, however, little is known about the developmental process, the architecture, and the changes that occur upon biofilm development. In the current study we made use of a continuous-culture biofilm system to characterize biofilm development of 14 different S. pneumoniae strains representing at least 10 unique serotypes. The biofilm development process was found to occur in three distinct stages, including initial attachment, cluster formation, and biofilm maturation. While all 14 pneumococcal strains displayed similar developmental stages, the mature biofilm architecture differed significantly among the serotypes tested. Overall, three biofilm architectural groups were detected based on biomass, biofilm thickness, and cluster size. The biofilm viable cell counts and total protein concentration increased steadily over the course of biofilm development, reaching ϳ8 ؋ 10 8 cells and ϳ15 mg of protein per biofilm after 9 days of biofilm growth. Proteomic analysis confirmed the presence of distinct biofilm developmental stages by the detection of multiple phenotypes over the course of biofilm development. The biofilm development process was found to correlate not only with differential production of proteins but also with a dramatic increase in the number of detectable proteins, indicating that biofilm formation by S. pneumoniae may be a far more complex process than previously anticipated. Protein identification revealed that proteins involved in virulence, adhesion, and resistance were more abundant under biofilm growth conditions. A possible role of the identified proteins in biofilm formation is discussed.Streptococcus pneumoniae is an important human pathogen that causes an array of diseases, including acute bacterial sinusitis, meningitis, and bacteremia, and remains the major cause of acute bacterial pneumonia and otitis media. Worldwide, approximately 1.1 million deaths annually are attributed to S. pneumoniae infection (42). S. pneumoniae is among the most common microorganisms isolated from otitis media specimens, others including Haemophilus influenzae, Moraxella catarrhalis, and Alliococcus otiditis (30). The gram-positive, opportunistic pathogen S. pneumoniae has been cultured from approximately 40% of middle-ear fluid samples taken from patients with acute otitis media (9, 24).Next to the common cold, otitis media is the most commonly diagnosed childhood illness in the United States. Otitis media is a clinical diagnosis and the most prevalent infectious disease in children, characterized by the accumulation of fluid in the middle-ear space. Approximately one-third of all children experience three or more episodes of acute otitis media by the age of 3 years (27). Conductive hearing loss is a major consequence of otitis media that may affect the child's behavior, education, or development of language ...

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Section: Discussionmentioning

confidence: 94%

Phenotypic Characterization ofStreptococcus pneumoniaeBiofilm Development

et al. 2006

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“…TNF-␣ levels were measured by a bioassay with the L929 fibrosarcoma cell line, as described previously (6). Briefly, confluent cells were thoroughly washed with Hanks solution (Biochrom AG, Berlin, Germany) and harvested with 0.25% thrypsin-0.02% EDTA (Biochrom AG).…”

Section: Animalsmentioning

confidence: 99%

Immunomodulatory Clarithromycin Treatment of Experimental Sepsis and Acute Pyelonephritis Caused by Multidrug-Resistant Pseudomonas aeruginosa

Giamarellos‐Bourboulis¹,

Adamis

Laoutaris³

et al. 2004

Antimicrob Agents Chemother

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Clarithromycin was administered intravenously to 55 rabbits to evaluate its effect on experimental sepsis caused by multidrug-resistant Pseudomonas aeruginosa. Acute pyelonephritis was induced after ligation of the right ureter and injection of 10 8 CFU of the test isolate per kg of body weight into the renal pelvis. The animals were divided into six groups: group A, controls; group B, rabbits that received one intravenous dose of 80 mg of clarithromycin per kg concomitantly with bacterial challenge; group C, rabbits that received two doses of clarithromycin, the second one of which was given 2 h after the first one; group D, rabbits that received 15 mg of amikacin per kg; group E, rabbits that received one dose of clarithromycin and amikacin; and group F, rabbits that received two doses of clarithromycin and amikacin. Serum endotoxin levels were estimated by the QCL-1000 Limulus amoebocyte lysate assay, tumor necrosis factor alpha (TNF-␣) levels were measured by a bioassay, and malondialdehyde (MDA) levels were measured by the thiobarbiturate assay. Viable bacterial counts in various tissue samples were also assessed. The mean survival times of the animals in groups A, B, C, D, E, and F were 4.50, 7.69, 4.07, 4.55, 11.55, and 11.60 days, respectively (P ‫؍‬ 0.033 for group D versus group F, P ‫؍‬ 0.006 for group D versus group E, P ‫؍‬ not significant for group B versus group E, P ‫؍‬ 0.042 for group C versus group F). Serum endotoxin levels were similar between groups at all sampling times; TNF-␣ and MDA levels in groups B, C, E, and F decreased significantly over follow-up. The numbers of viable bacterial cells in the infected kidney were similar among the groups; those in the liver, spleen, lungs, and mesenteral lymph nodes were significantly decreased in groups B, E, and F compared to those in groups A and D. It is concluded that a prolongation of survival in animals with experimental sepsis caused by multidrug-resistant P. aeruginosa was achieved after coadministration of clarithromycin and amikacin and that the increased survival was probably attributable to the immunomodulatory properties of clarithromycin.Clarithromycin is a macrolide classically known to possess an antimicrobial spectrum that includes gram-positive cocci and atypical pathogens (23). However, an increasing body of evidence suggests that clarithromycin possesses considerable antiinflammatory and immunomodulatory properties, recommending its administration for the treatment of chronic inflammatory conditions like diffuse panbronchiolitis and cystic fibrosis (11,21,26). Its immunomodulatory properties are observed in vitro at concentrations close to 10 g/ml (14). On the basis of that finding, intravenous administration of clarithromycin leading to the same levels in blood might be beneficial for the treatment of an acute inflammatory state like sepsis.Pseudomonas aeruginosa is a common pathogen that is involved in nosocomial sepsis and that is often characterized nowadays by multidrug resistance (18). In the present study, intravenous clar...

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“…Several other studies have measured CSF TNF-␣ and IL-1 levels in pneumococcal meningitis (2,3,5,6,14,26). To our knowledge, only two of these have measured CSF cytokine kinetics in samples taken every second to fourth hour, as in our study.…”

Section: Discussionmentioning

confidence: 88%

Inhibition of Leukocyte Entry into the Brain by the Selectin Blocker Fucoidin Decreases Interleukin-1 (IL-1) Levels but Increases IL-8 Levels in Cerebrospinal Fluid during Experimental Pneumococcal Meningitis in Rabbits

et al. 2000

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The polysaccharide fucoidin is a selectin blocker that inhibits leukocyte recruitment into the cerebrospinal fluid (CSF) during experimental pneumococcal meningitis. In the present study, the effect of fucoidin treatment on the release of the proinflammatory cytokines tumor necrosis factor alpha (TNF-␣), interleukin-1 (IL-1), and IL-8 into the CSF was investigated. Rabbits (n ‫؍‬ 7) were treated intravenously with 10 mg of fucoidin/kg of body weight every second hour starting 4 h after intracisternal inoculation of ϳ10 6 CFU of Streptococcus pneumoniae type 3 (untreated control group, n ‫؍‬ 7). CSF samples were obtained every second hour during a 16-h study period. Treatment with fucoidin caused a consistent and significant decrease in CSF IL-1 levels (in picograms per milliliter) between 12 and 16 h (0 versus 170, 0 versus 526, and 60 versus 1,467, respectively; P < 0.02). A less consistent decrease in CSF TNF-␣ levels was observed in the fucoidin-treated group, but with no significant difference between the two groups (P > 0.05). In contrast, there was no attenuation in CSF IL-8 levels. Indeed, there was a significant increase in CSF IL-8 levels (in picograms per milliliter) in the fucoidin-treated group at 10 and 12 h (921 versus 574 and 1,397 versus 569, respectively; P < 0.09). In conclusion, our results suggest that blood-derived leukocytes mainly are responsible for the release of IL-1 and to some degree TNF-␣ into the CSF during pneumococcal meningitis, whereas IL-8 may be produced by local cells within the brain.

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Serotype‐Related Differences in Inflammatory Response toStreptococcus pneumoniaein Experimental Meningitis

Cited by 47 publications

References 14 publications

Phenotypic Characterization ofStreptococcus pneumoniaeBiofilm Development

Phenotypic Characterization ofStreptococcus pneumoniaeBiofilm Development

Immunomodulatory Clarithromycin Treatment of Experimental Sepsis and Acute Pyelonephritis Caused by Multidrug-Resistant Pseudomonas aeruginosa

Inhibition of Leukocyte Entry into the Brain by the Selectin Blocker Fucoidin Decreases Interleukin-1 (IL-1) Levels but Increases IL-8 Levels in Cerebrospinal Fluid during Experimental Pneumococcal Meningitis in Rabbits

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