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Haemophilus influenzae responds to glucocorticoids used in asthma therapy by modulation of biofilm formation and antibiotic resistance.

Earl CS, Keong TW, An SQ, Murdoch S, McCarthy Y, Garmendia J, Ward J, Dow JM, Yang L, O'Toole GA, Ryan RP - EMBO Mol Med (2015)

Bottom Line: Glucocorticosteroids are used as a main treatment to reduce airway inflammation in people with asthma who suffer from neutrophilic airway inflammation, a condition frequently associated with Haemophilus influenzae colonization.Here we show that glucocorticosteroids have a direct influence on the behavior of H. influenzae that may account for associated difficulties with therapy.Taken together, these data strongly suggest that H. influenzae can respond directly to corticosteroid treatment in the airway potentially influencing biofilm formation, persistence and the efficacy of antibiotic treatment.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee, UK.

No MeSH data available.


Related in: MedlinePlus

Corticosteroid treatment affects H. influenzae clearance by antibiotic treatment in the mouse airwayA, B Mice infected intranasally with 1 × 108 CFU H. influenzae and treated by inhaling PBS with or without 50 μM beclomethasone. Azithromycin was administered at a concentration of 100 mg/kg/24 h, daily for 3 days after infection. On day 3–4 after infection, the mice were harvested, and bacterial loads were determined in lung (A) and spleen (B) homogenates. Values represent the mean ± standard deviation (SD). The data are pooled from three independent experiments. Statistical significance by two-tailed Student’s t-test is indicated: *P < 0.05, **P < 0.01.
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fig06: Corticosteroid treatment affects H. influenzae clearance by antibiotic treatment in the mouse airwayA, B Mice infected intranasally with 1 × 108 CFU H. influenzae and treated by inhaling PBS with or without 50 μM beclomethasone. Azithromycin was administered at a concentration of 100 mg/kg/24 h, daily for 3 days after infection. On day 3–4 after infection, the mice were harvested, and bacterial loads were determined in lung (A) and spleen (B) homogenates. Values represent the mean ± standard deviation (SD). The data are pooled from three independent experiments. Statistical significance by two-tailed Student’s t-test is indicated: *P < 0.05, **P < 0.01.

Mentions: Using a slight modification of the mouse model described above (see Materials and Methods), the C57BL/6 mice were infected with 1 × 108 CFU of H. influenzae and treated by inhaling PBS with or without 50 μM beclomethasone. Azithromycin was administered at a concentration of 100 mg/kg/24 h, a dose reported by several studies (Azoulay-Dupuis et al, 1991; Girard et al, 2005). The lung and spleen bacterial load was determined 3 days post-infection. C57BL/6 mice infected with H. influenzae with PBS exhibited considerable colonization (Fig6A and B). Azithromycin appeared to be very effective in eradicating H. influenzae from mice treated with PBS alone (Fig6A and B). However, with the addition of beclomethasone, bacteria appear to be present even after the mice had received 3 days of azithromycin treatment (Fig6A and B).


Haemophilus influenzae responds to glucocorticoids used in asthma therapy by modulation of biofilm formation and antibiotic resistance.

Earl CS, Keong TW, An SQ, Murdoch S, McCarthy Y, Garmendia J, Ward J, Dow JM, Yang L, O'Toole GA, Ryan RP - EMBO Mol Med (2015)

Corticosteroid treatment affects H. influenzae clearance by antibiotic treatment in the mouse airwayA, B Mice infected intranasally with 1 × 108 CFU H. influenzae and treated by inhaling PBS with or without 50 μM beclomethasone. Azithromycin was administered at a concentration of 100 mg/kg/24 h, daily for 3 days after infection. On day 3–4 after infection, the mice were harvested, and bacterial loads were determined in lung (A) and spleen (B) homogenates. Values represent the mean ± standard deviation (SD). The data are pooled from three independent experiments. Statistical significance by two-tailed Student’s t-test is indicated: *P < 0.05, **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4551341&req=5

fig06: Corticosteroid treatment affects H. influenzae clearance by antibiotic treatment in the mouse airwayA, B Mice infected intranasally with 1 × 108 CFU H. influenzae and treated by inhaling PBS with or without 50 μM beclomethasone. Azithromycin was administered at a concentration of 100 mg/kg/24 h, daily for 3 days after infection. On day 3–4 after infection, the mice were harvested, and bacterial loads were determined in lung (A) and spleen (B) homogenates. Values represent the mean ± standard deviation (SD). The data are pooled from three independent experiments. Statistical significance by two-tailed Student’s t-test is indicated: *P < 0.05, **P < 0.01.
Mentions: Using a slight modification of the mouse model described above (see Materials and Methods), the C57BL/6 mice were infected with 1 × 108 CFU of H. influenzae and treated by inhaling PBS with or without 50 μM beclomethasone. Azithromycin was administered at a concentration of 100 mg/kg/24 h, a dose reported by several studies (Azoulay-Dupuis et al, 1991; Girard et al, 2005). The lung and spleen bacterial load was determined 3 days post-infection. C57BL/6 mice infected with H. influenzae with PBS exhibited considerable colonization (Fig6A and B). Azithromycin appeared to be very effective in eradicating H. influenzae from mice treated with PBS alone (Fig6A and B). However, with the addition of beclomethasone, bacteria appear to be present even after the mice had received 3 days of azithromycin treatment (Fig6A and B).

Bottom Line: Glucocorticosteroids are used as a main treatment to reduce airway inflammation in people with asthma who suffer from neutrophilic airway inflammation, a condition frequently associated with Haemophilus influenzae colonization.Here we show that glucocorticosteroids have a direct influence on the behavior of H. influenzae that may account for associated difficulties with therapy.Taken together, these data strongly suggest that H. influenzae can respond directly to corticosteroid treatment in the airway potentially influencing biofilm formation, persistence and the efficacy of antibiotic treatment.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee, UK.

No MeSH data available.


Related in: MedlinePlus