scholarly journals Glycolytic Metabolism Is Critical for the Innate Antibacterial Defense in Acute Streptococcus pneumoniae Otitis Media

2021 ◽  
Vol 12 ◽  
Author(s):  
Fangmei Fan ◽  
Yurong Ma ◽  
Rongshuang Ai ◽  
Zhiqiang Ding ◽  
Dingyi Li ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Inflammatory Response ◽  
Otitis Media ◽  
Middle Ear ◽  
Acute Otitis Media ◽  
Metabolic Reprogramming ◽  
Respiratory Pathogen ◽  
Enzyme Linked Immunosorbent Assay ◽  
Glycolytic Metabolism ◽  
Ear Injury

ObjectiveStreptococcus pneumoniae (S.pn) is a common respiratory pathogen and a frequent cause of acute otitis media (AOM) in children. However, little is known about the immunometabolism during AOM. This study was to assess the presence of glucose metabolic reprogramming during AOM and its underlying mechanism affecting inflammatory response and middle ear injury.MethodsThe levels of glycolytic metabolism were evaluated by measuring the expression of glycolysis-related genes and the production of metabolites. HE stain, immunofluorescence, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and Western blot were performed to measure the effect of glucose metabolic reprogramming on inflammatory response, pneumococcal clearance, hypoxia-inducible factor 1 alpha (HIF-1α) expression and cytokine secretion during AOM, respectively.ResultsThe analysis of microarray revealed an increase of the expression of glycolysis-related genes during S.pn–induced AOM, which was verified by real-time PCR. Increased glycolysis promoted the production of IL-1β and TNF-α and facilitated the clearance of S.pn by enhancing phagocytosis and killing capability of neutrophils, but also aggravated the middle ear injury. Furthermore, these pathogenic effects could be reversed after glycolytic inhibitor 2DG treatment. Additionally, HIF-1α was observed to involve in glycolytic metabolism during AOM.ConclusionS.pn infection induced increased glycolysis conversion during AOM, which promoted inflammatory responses and bacterial clearance, but also aggravated tissue damage.

Overexpression of immune-responsive gene 1 prevents acute otitis media due to streptococcus pneumoniae infection through Nrf2- Hmox1 pathway

2019 ◽  
Author(s):  
Peizhen Yang ◽  
Yufen Li ◽  
Dongqing Wang ◽  
Zhipeng Chen
Keyword(s):  
Streptococcus Pneumoniae ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Otitis Media ◽  
Middle Ear ◽  
Acute Otitis Media ◽  
Lavage Fluid ◽  
Mice Model ◽  
Nrf2 Signaling Pathway ◽  
Positive Rate

Abstract Background: Acute otitis media (AOM) is one of the most commonly diagnosed childhood diseases that are associated with influenza infection. Immunoresponsive gene 1 (Irg1) is overexpressed in mammalian macrophage during inflammation process. Here, the present study aims to investigate the role of Irg1 in streptococcus pneumoniae infection-induced inflammatory response in AOM through Nrf2 signaling pathway. Methods: Positive rate of streptococcus pneumoniae and expression of Irg1, Nrf2 and Hmox1 were determined in the middle ear lavage fluid from 85 AOM patients infected with streptococcus pneumoniae and 48 healthy subjects. After the successful establishment of mice model with AOM, macrophage was harvest from the middle ear lavage fluid of mice. At last, to investigate the effect of Irg1 and Nrf2 signaling pathway on inflammatory response and streptococcus pneumoniae infection by accumulating macrophage, Irg1, sh-Irg1 and retinoic acid (an inhibitor of Nrf2 signaling pathway) were injected into AOM mice. Results: Irg1 exhibited a high level and activated Nrf2 signaling pathway was detected in AOM. Besides, positive rate of streptococcus pneumoniae was increased in AOM. Furthermore, in the mice model with AOM, Irg1 could repress inflammatory response by downregulating expression of TNF-α, IL-6 and IL-1β and inhibit streptococcus pneumoniae infection by stimulating accumulation of macrophage to increase its endocytosis through activation of Nrf2 signaling pathway. Conclusion: Taken together, Irg1 contributes to inhibiting inflammatory response and streptococcus pneumoniae infection in AOM by promoting accumulation of macrophage through activation of Nrf2 signaling pathway, which provides novel therapeutic targets for AOM therapy.

MIDDLE-EAR FLUID STREPTOCOCCUS PNEUMONIAE SUSCEPTIBILITY AND SEROTYPE AND DISTRIBUTION IN MEXICAN CHILDREN WITH ACUTE OTITIS MEDIA

PEDIATRICS ◽  
2008 ◽  
Vol 121 (Supplement 2) ◽  
pp. S129.2-S129 ◽  
Author(s):  
Claudia Lopez-Enriquez ◽  
A. Blanco-Montero ◽  
L. E. Espinosa-Monteros ◽  
R. Rodriguez ◽  
C. De La Torre ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Otitis Media ◽  
Middle Ear ◽  
Acute Otitis Media ◽  
Mexican Children ◽  
Middle Ear Fluid

scholarly journals Streptococcus pneumoniae Isolates from Middle Ear Fluid and Nasopharynx of Children with Acute Otitis Media Exhibit Phase Variation

2011 ◽  
Vol 49 (4) ◽  
pp. 1646-1649 ◽  
Author(s):  
J. Arai ◽  
M. Hotomi ◽  
S. K. Hollingshead ◽  
Y. Ueno ◽  
D. E. Briles ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Otitis Media ◽  
Middle Ear ◽  
Acute Otitis Media ◽  
Phase Variation ◽  
Middle Ear Fluid

Experimental otitis media after nasal inoculation of Streptococcus pneumoniae and influenza A virus in chinchillas

1980 ◽  
Vol 30 (2) ◽  
pp. 445-450
Author(s):  
G S Giebink ◽  
I K Berzins ◽  
S C Marker ◽  
G Schiffman
Keyword(s):  
Streptococcus Pneumoniae ◽  
Otitis Media ◽  
Influenza A Virus ◽  
Middle Ear ◽  
Influenza A ◽  
Acute Otitis Media ◽  
Aerobic Bacteria ◽  
Middle Ear Effusion ◽  
Respiratory Viral Infection ◽  
Ear Effusion

Otitis media developed in 67% of chinchillas inoculated intranasally with type 7 Streptococcus pneumoniae and influenza A virus. Only 4% of chinchillas inoculated with influenza alone and 21% of chinchillas inoculated with S. pneumoniae alone developed otitis media. Among the chinchillas that developed otitis media after inoculation with both pneumococcus and influenza, 73% of the affected ears contained effusion, and 27% of the affected ears showed tympanic membrane inflammation without middle ear effusion obtained on paracentesis. Although a majority of the ears with effusion yielded S. pneumoniae on culture, one-third of the effusions were sterile for aerobic bacteria. This model resembles conditions accompanying otitis media in humans and suggests that respiratory viral infection contributes significantly to the pathogenesis of acute otitis media.

Immunologic Characteristics of Cytokines in Otitis Media with Effusion

1992 ◽  
Vol 101 (10_suppl) ◽  
pp. 21-25 ◽  
Author(s):  
Tetsuo Himi ◽  
Toshio Suzuki ◽  
Hiroyuki Takezawa ◽  
Hiroyuki Kodama ◽  
Akikatsu Kataura
Keyword(s):  
Otitis Media ◽  
Middle Ear ◽  
Otitis Media With Effusion ◽  
Acute Otitis Media ◽  
Chronic Otitis Media ◽  
Inflammatory Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Gm Csf ◽  
Cytologic Analysis ◽  
Macrophage Colony

Levels of cytokines, interleukin (IL)–1α, IL-1β, tumor necrosis factor (TNF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were investigated in samples of the middle ear effusions (MEEs) from 144 ears with otitis media with effusion (OME) by enzyme-linked immunosorbent assay, followed by cytologic analysis. Middle ear effusions of the acute purulent type contained a significantly higher concentration of cytokines compared with normal control sera (p < .001). Cytokines were observed at lower levels in MEE in adults than in children. Tests of children at the chronic stage of MEE showed higher levels of TNF than IL-1 and GM-CSF. Meanwhile, IL-1β showed significantly higher concentrations in acute purulent types than in serous and mucoid types (p < .01). In cytologic analysis, the mean level of IL-1β was significantly higher in the neutrophil-rich group than in other groups (p < .05). Cytokines possess several biologic properties, some of which are associated not only with acute otitis media but also with chronic otitis media. This study showed that cytokines, especially IL-1β, contribute to infiltration into the middle ear by inflammatory cells. This implies that the persistent presence of cytokines in MEE could be a factor in prolonged OME.

A new technique (the NOW test) for the detection of Streptococcus pneumoniae in the effusions of otitis media

2002 ◽  
Vol 116 (7) ◽  
pp. 499-501 ◽  
Author(s):  
Howard Faden ◽  
Christopher Poje ◽  
Michael Pizzuto ◽  
Mark Nagy ◽  
Linda Brodsky
Keyword(s):  
Streptococcus Pneumoniae ◽  
Otitis Media ◽  
Middle Ear ◽  
Acute Otitis Media ◽  
Chronic Otitis Media ◽  
Urinary Antigen Test ◽  
Pneumococcal Antigen ◽  
A New Technique ◽  
Culture Positive ◽  
Culture Negative

The presence of Streptococcus pneumoniae in chronic otitis media was determined with a new antigen detection kit, the NOW test. The NOW test was originally designed as a urinary antigen test but was adapted to middle-ear effusions for the present study. Middle-ear effusions from 52 children were studied. Streptococcus pneumoniae was cultured from 10 per cent of the effusions. The NOW test was positive in 23 per cent of the effusions, 80 per cent of culture positive and 17 per cent of culture negative effusions. The NOW test proved to be rapid, simple, reliable and relatively inexpensive for the detection of pneumococcal antigen in the middle-ear effusions. This test may prove valuable for the management of children with acute otitis media who undergo tympanocentesis.

scholarly journals In Vitro Activities of Cethromycin (ABT-773), a New Ketolide, against Streptococcus pneumoniae Strains That Are Not Susceptible to Penicillin or Macrolides

2003 ◽  
Vol 47 (1) ◽  
pp. 166-169 ◽  
Author(s):  
Edward O. Mason ◽  
Linda B. Lamberth ◽  
Ellen R. Wald ◽  
John S. Bradley ◽  
William J. Barson ◽  
...  
Keyword(s):  
United States ◽  
Streptococcus Pneumoniae ◽  
Otitis Media ◽  
Middle Ear ◽  
Acute Otitis Media ◽  
The United States ◽  
Macrolide Resistance ◽  
Broth Microdilution ◽  
Time Period

ABSTRACT Pneumococcal resistance to antimicrobials presents problems to physicians for empirical treatment of acute otitis media (AOM). Three hundred thirty-three isolates of Streptococcus pneumoniae selected for nonsusceptibility to penicillin (MIC >0.1 μg/ml) from the middle ear (n = 325) or mastoid (n = 8) of children seen between 1994 and 2000 at four children's hospitals in the United States were tested by broth microdilution for susceptibility to nine antibiotics. Using NCCLS 2002 breakpoints, resistance to the following drugs was as indicated: amoxicillin, 1%; azithromycin, 71%; cefprozil, 71%; ceftriaxone, 2%; cefdinir, 98%; erythromycin, 70%; levofloxacin, 0%; and trimethoprim-sulfamethoxazole, 93%. Of the penicillin- and erythromycin-nonsusceptible isolates, 97% were inhibited by cethromycin (ABT-773) and 83% were inhibited by telithromycin at a concentration of ≤0.125 μg/ml. Macrolide resistance among penicillin-nonsusceptible pneumococci increased from 44 to 80% in the 6 years of the study from which the isolates were selected; however, the proportion of isolates with M or MLSB phenotypes remained constant over the time period (53 and 18%, respectively). Prior treatment with a macrolide or clindamycin alone or in combination with a β-lactam resulted in 94 or 85% of isolates causing infections being macrolide and or clindamycin resistant. No prior individual macrolide (azithromycin, erythromycin, or clarithromycin) resulted in more macrolide resistance or in a more prevalent resistance phenotype. The ketolides appear to be active antimicrobials against penicillin- and macrolide-resistant pneumococci.

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