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Low concentrations of nitric oxide modulate Streptococcus pneumoniae biofilm metabolism and antibiotic tolerance

Low concentrations of nitric oxide modulate Streptococcus pneumoniae biofilm metabolism and antibiotic tolerance
Low concentrations of nitric oxide modulate Streptococcus pneumoniae biofilm metabolism and antibiotic tolerance
Streptococcus pneumoniae is one of the key pathogens responsible for otitis media (OM), the most common infection in children and the largest cause of childhood antibiotic prescription. Novel therapeutic strategies that reduce the overall antibiotic consumption due to OM are required because although widespread pneumococcal conjugate immunization has controlled invasive pneumococcal disease, overall OM incidence has not decreased. Biofilm formation represents an important phenotype contributing to the antibiotic tolerance and persistence of S. pneumoniae in chronic or recurrent OM. We investigated the treatment of pneumococcal biofilms with nitric oxide (NO), an endogenous signaling molecule and therapeutic agent that has been demonstrated to trigger biofilm dispersal in other bacterial species. We hypothesised that addition of low concentrations of NO to pneumococcal biofilms would improve antibiotic efficacy and higher concentrations exert direct antibacterial effects. Unlike in many other bacterial species, low concentrations of NO, did not result in S. pneumoniae biofilm dispersal. Instead, treatment of both in vitro biofilms and ex vivo adenoid tissue samples (a reservoir for S. pneumoniae biofilms) with low concentrations of NO enhanced pneumococcal killing when combined with amoxicillin-clavulanic acid, an antibiotic commonly used to treat chronic OM. Quantitative proteomic analysis using iTRAQ (isobaric tag for relative and absolute quantitation) identified 13 proteins that were differentially expressed following low-concentration NO treatment, 85% of which function in metabolism or translation. Treatment with low-concentration NO therefore appears to modulate pneumococcal metabolism and may represent a novel therapeutic approach to reduce antibiotic tolerance in pneumococcal biofilms.
low, concentrations, nitric, oxide, modulate, streptococcus, pneumoniaebiofilm, metabolism, antibiotic tolerance
0066-4804
2456-2466
Allan, Raymond N.
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Morgan, Samantha
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Brito-Mutunayagam, Sanjita
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Skipp, Paul
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Feelisch, Martin
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Hayes, Stephen M.
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Hellier, William
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Clarke, Stuart C.
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Stoodley, Paul
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Burgess, Andrea
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Ismail-Koch, Hasnaa
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Salib, Rami J.
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Webb, Jeremy S.
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Faust, Saul N.
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Hall-Stoodley, Luanne
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Allan, Raymond N.
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Morgan, Samantha
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Brito-Mutunayagam, Sanjita
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Skipp, Paul
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Feelisch, Martin
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Hayes, Stephen M.
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Hellier, William
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Clarke, Stuart C.
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Stoodley, Paul
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Burgess, Andrea
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Ismail-Koch, Hasnaa
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Salib, Rami J.
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Webb, Jeremy S.
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Faust, Saul N.
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Hall-Stoodley, Luanne
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Allan, Raymond N., Morgan, Samantha, Brito-Mutunayagam, Sanjita, Skipp, Paul, Feelisch, Martin, Hayes, Stephen M., Hellier, William, Clarke, Stuart C., Stoodley, Paul, Burgess, Andrea, Ismail-Koch, Hasnaa, Salib, Rami J., Webb, Jeremy S., Faust, Saul N. and Hall-Stoodley, Luanne (2016) Low concentrations of nitric oxide modulate Streptococcus pneumoniae biofilm metabolism and antibiotic tolerance. Antimicrobial Agents and Chemotherapy, 60 (4), 2456-2466. (doi:10.1128/AAC.02432-15). (PMID:26856845)

Record type: Article

Abstract

Streptococcus pneumoniae is one of the key pathogens responsible for otitis media (OM), the most common infection in children and the largest cause of childhood antibiotic prescription. Novel therapeutic strategies that reduce the overall antibiotic consumption due to OM are required because although widespread pneumococcal conjugate immunization has controlled invasive pneumococcal disease, overall OM incidence has not decreased. Biofilm formation represents an important phenotype contributing to the antibiotic tolerance and persistence of S. pneumoniae in chronic or recurrent OM. We investigated the treatment of pneumococcal biofilms with nitric oxide (NO), an endogenous signaling molecule and therapeutic agent that has been demonstrated to trigger biofilm dispersal in other bacterial species. We hypothesised that addition of low concentrations of NO to pneumococcal biofilms would improve antibiotic efficacy and higher concentrations exert direct antibacterial effects. Unlike in many other bacterial species, low concentrations of NO, did not result in S. pneumoniae biofilm dispersal. Instead, treatment of both in vitro biofilms and ex vivo adenoid tissue samples (a reservoir for S. pneumoniae biofilms) with low concentrations of NO enhanced pneumococcal killing when combined with amoxicillin-clavulanic acid, an antibiotic commonly used to treat chronic OM. Quantitative proteomic analysis using iTRAQ (isobaric tag for relative and absolute quantitation) identified 13 proteins that were differentially expressed following low-concentration NO treatment, 85% of which function in metabolism or translation. Treatment with low-concentration NO therefore appears to modulate pneumococcal metabolism and may represent a novel therapeutic approach to reduce antibiotic tolerance in pneumococcal biofilms.

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Antimicrob. Agents Chemother.-2016-Allan-AAC.02432-15.pdf - Other
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Accepted/In Press date: 5 February 2016
e-pub ahead of print date: 8 February 2016
Keywords: low, concentrations, nitric, oxide, modulate, streptococcus, pneumoniaebiofilm, metabolism, antibiotic tolerance
Organisations: nCATS Group

Identifiers

Local EPrints ID: 388499
URI: http://eprints.soton.ac.uk/id/eprint/388499
ISSN: 0066-4804
PURE UUID: 243732d6-c6ce-4782-9aaa-160f90d11d46
ORCID for Paul Skipp: ORCID iD orcid.org/0000-0002-2995-2959
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158
ORCID for Stuart C. Clarke: ORCID iD orcid.org/0000-0002-7009-1548
ORCID for Paul Stoodley: ORCID iD orcid.org/0000-0001-6069-273X
ORCID for Rami J. Salib: ORCID iD orcid.org/0000-0002-6753-7844
ORCID for Jeremy S. Webb: ORCID iD orcid.org/0000-0003-2068-8589
ORCID for Saul N. Faust: ORCID iD orcid.org/0000-0003-3410-7642

Catalogue record

Date deposited: 26 Feb 2016 15:02
Last modified: 17 Dec 2019 02:02

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