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

Autor:	Dawe H; Clinical and Experimental Sciences, Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK., Berger E; Proteomics Core Facility, University of Gothenburg, Gothenburg, Sweden., Sihlbom C; Proteomics Core Facility, University of Gothenburg, Gothenburg, Sweden., Angus EM; Biomedical Imaging Unit, Southampton General Hospital, Southampton, UK., Howlin RP; Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK.; Centre for Biological Sciences, University of Southampton, Southampton, UK., Laver JR; Clinical and Experimental Sciences, Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK., Tebruegge M; Clinical and Experimental Sciences, Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK.; Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK.; Global Health Research Institute, University of Southampton, Southampton, UK., Hall-Stoodley L; Department of Microbial Infection and Immunity, Centre for Microbial Interface Biology, College of Medicine, The Ohio State University, Columbus, Ohio, USA., Stoodley P; Department of Microbial Infection and Immunity, Centre for Microbial Interface Biology, College of Medicine, The Ohio State University, Columbus, Ohio, USA.; National Center for Advanced Tribology at Southampton (nCATS), Faculty of Engineering and the Environment, University of Southampton, UK., Faust SN; Clinical and Experimental Sciences, Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK.; Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK.; Southampton NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK., Allan RN; Southampton NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK.; Clinical and Experimental Sciences, Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK.
Jazyk:	angličtina
Zdroj:	Microbiology (Reading, England) [Microbiology (Reading)] 2017 Jul; Vol. 163 (7), pp. 1093-1104. Date of Electronic Publication: 2017 Jul 21.
DOI:	10.1099/mic.0.000491
Abstrakt:	Non-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.
Databáze:	MEDLINE
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