D-methionine interferes with non-typeable Haemophilus influenzae peptidoglycan synthesis during growth and biofilm formation

dc.cclicenceCC-BY-NC-NDen
dc.contributor.authorDawe, H.
dc.contributor.authorBerger, E.
dc.contributor.authorSihlbom, C.
dc.contributor.authorAngus, E. M.
dc.contributor.authorHowlin, R. P.
dc.contributor.authorLaver, J. R.
dc.contributor.authorTebruegge, M.
dc.contributor.authorHall-Stoodley, L.
dc.contributor.authorStoodley, P.
dc.contributor.authorFaust, S. N.
dc.contributor.authorAllan, Raymond N.
dc.date.acceptance2017-05-26
dc.date.accessioned2019-09-02T10:41:21Z
dc.date.available2019-09-02T10:41:21Z
dc.date.issued2017-07-12
dc.descriptionopen access articleen
dc.description.abstractNon-typeable Haemophilus influenzae (NTHi) is an opportunistic pathogen that plays a major role in a number of respiratory tract infections, including otitis media, cystic fibrosis and chronic obstructive pulmonary disease. Biofilm formation has been implicated in both NTHi colonization and disease, and is responsible for the increased tolerance of this pathogen towards antibiotic treatment. Targeting metabolic pathways that are important in NTHi biofilm formation represents a potential strategy to combat this antibiotic recalcitrance. A previous investigation demonstrated increased expression of a putative D-methionine uptake protein following exposure of NTHi biofilms to the ubiquitous signalling molecule, nitric oxide. We therefore hypothesized that treatment with exogenous D-methionine would impact on NTHi biofilm formation and increase antibiotic sensitivity. Treatment of NTHi during the process of biofilm formation resulted in a reduction in biofilm viability, increased biomass, changes in the overall biofilm architecture and the adoption of an amorphous cellular morphology. Quantitative proteomic analyses identified 124 proteins that were differentially expressed following D-methionine treatment, of which 51 (41 %) were involved in metabolic and transport processes. Nine proteins involved in peptidoglycan synthesis and cell division showed significantly increased expression. Furthermore, D-methionine treatment augmented the efficacy of azithromycin treatment and highlighted the potential of D-methionine as an adjunctive therapeutic approach for NTHi biofilm-associated infections.en
dc.exception.ref2021codes254aen
dc.funderNo external funderen
dc.identifier.citationDawe, H. et al. (2017) D-methionine interferes with non-typeable Haemophilus influenzae peptidoglycan synthesis during growth and biofilm formation. Microbiology, 163 (7)en
dc.identifier.doihttps://doi.org/10.1099/mic.0.000491
dc.identifier.urihttps://www.dora.dmu.ac.uk/handle/2086/18386
dc.language.isoenen
dc.peerreviewedYesen
dc.publisherMicrobiology Societyen
dc.researchinstituteLeicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)en
dc.subjectD-methionineen
dc.subjectHaemophilus influenzaeen
dc.subjectBiofilmen
dc.subjectpeptidoglycanen
dc.titleD-methionine interferes with non-typeable Haemophilus influenzae peptidoglycan synthesis during growth and biofilm formationen
dc.typeArticleen

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