Imperial College London

ProfessorSebastianJohnston

Faculty of MedicineNational Heart & Lung Institute

Asthma UK Clinical Chair
 
 
 
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Contact

 

+44 (0)20 7594 3764s.johnston

 
 
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Assistant

 

Mr Christophe Tytgat +44 (0)20 7594 3849

 
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Location

 

343Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Porter:2016:jac/dkw222,
author = {Porter, JD and Watson, J and Groves, H and Dhariwal, J and Almond, MH and Wong, E and Walton, RP and Tregoning, J and Kilty, I and Johnston, SL and Edwards, MR},
doi = {jac/dkw222},
journal = {Journal of Antimicrobial Chemotherapy},
pages = {2767--2781},
title = {Identification of novel macrolides with antibacterial, anti-inflammatory and type I and III IFN-augmenting activity in airway epithelium},
url = {http://dx.doi.org/10.1093/jac/dkw222},
volume = {71},
year = {2016}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Background Exacerbations of asthma and COPD are triggered by rhinoviruses. Uncontrolled inflammatory pathways, pathogenic bacterial burden and impaired antiviral immunity are thought to be important factors in disease severity and duration. Macrolides including azithromycin are often used to treat the above diseases, but exhibit variable levels of efficacy. Inhaled corticosteroids are also readily used in treatment, but may lack specificity. Ideally, new treatment alternatives should suppress unwanted inflammation, but spare beneficial antiviral immunity.Methods In the present study, we screened 225 novel macrolides and tested them for enhanced antiviral activity against rhinovirus, as well as anti-inflammatory activity and activity against Gram-positive and Gram-negative bacteria. Primary bronchial epithelial cells were grown from 10 asthmatic individuals and the effects of macrolides on rhinovirus replication were also examined. Another 30 structurally similar macrolides were also examined.Results The oleandomycin derivative Mac5, compared with azithromycin, showed superior induction (up to 5-fold, EC50=5–11 μM) of rhinovirus-induced type I IFNβ, type III IFNλ1 and type III IFNλ2/3 mRNA and the IFN-stimulated genes viperin and MxA, yet had no effect on IL-6 and IL-8 mRNA. Mac5 also suppressed rhinovirus replication at 48 h, proving antiviral activity. Mac5 showed antibacterial activity against Gram-positive Streptococcus pneumoniae; however, it did not have any antibacterial properties compared with azithromycin when used against Gram-negative Escherichia coli (as a model organism) and also the respiratory pathogens Pseudomonas aeruginosa and non-typeable Haemophilus influenzae. Further non-toxic Mac5 derivatives were identified with various anti-inflammatory, antiviral and antibacterial activities.Conclusions The data support the idea that macrolides have antiviral properties through a mechanism that is yet to be ascertained. We also
AU - Porter,JD
AU - Watson,J
AU - Groves,H
AU - Dhariwal,J
AU - Almond,MH
AU - Wong,E
AU - Walton,RP
AU - Tregoning,J
AU - Kilty,I
AU - Johnston,SL
AU - Edwards,MR
DO - jac/dkw222
EP - 2781
PY - 2016///
SN - 1460-2091
SP - 2767
TI - Identification of novel macrolides with antibacterial, anti-inflammatory and type I and III IFN-augmenting activity in airway epithelium
T2 - Journal of Antimicrobial Chemotherapy
UR - http://dx.doi.org/10.1093/jac/dkw222
UR - http://hdl.handle.net/10044/1/38908
VL - 71
ER -