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

dc.cclicenceCC-BY-NC-NDen
dc.contributor.authorAllan, Raymond N.
dc.contributor.authorMorgan, S.
dc.contributor.authorBrito-Mutunayagam, S.
dc.contributor.authorSkipp, P.
dc.contributor.authorFeelisch, M.
dc.contributor.authorHayes, S. M.
dc.contributor.authorHellier, W.
dc.contributor.authorClarke, S. C.
dc.contributor.authorStoodley, P.
dc.contributor.authorBurgess, A.
dc.contributor.authorIsmail-Koch, H.
dc.contributor.authorSalib, R. J.
dc.contributor.authorWebb, J. S.
dc.contributor.authorFaust, S. N.
dc.contributor.authorHall-Stoodley, L.
dc.date.acceptance2016-02-05
dc.date.accessioned2019-09-02T09:30:39Z
dc.date.available2019-09-02T09:30:39Z
dc.date.issued2016-03-25
dc.descriptionThe file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.en
dc.description.abstractStreptococcus 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 hypothesized that addition of low concentrations of NO to pneumococcal biofilms would improve antibiotic efficacy and that 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.en
dc.exception.ref2021codes254aen
dc.funderOther external funder (please detail below)en
dc.funder.otherSparks Children's Medical Research Charityen
dc.identifier.citationAllan, Raymond N. et al. (2016) Low Concentrations of Nitric Oxide Modulate Streptococcus pneumoniae Biofilm Metabolism and Antibiotic Tolerance. Antimicrobial Agents and Chemotherapy, 60, pp. 2456-2466en
dc.identifier.doihttps://doi.org/10.1128/aac.02432-15
dc.identifier.urihttps://www.dora.dmu.ac.uk/handle/2086/18382
dc.language.isoenen
dc.peerreviewedYesen
dc.projectid11STH01en
dc.publisherAmerican Society for Microbiologyen
dc.researchinstituteLeicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)en
dc.subjectNitric oxideen
dc.subjectStreptococcus pneumoniaeen
dc.subjectBiofilmen
dc.titleLow concentrations of nitric oxide modulate Streptococcus pneumoniae biofilm metabolism and antibiotic toleranceen
dc.typeArticleen

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