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

D-methionine interferes with non-typeable Haemophilus influenzae peptidoglycan synthesis during growth and biofilm formation
D-methionine interferes with non-typeable Haemophilus influenzae peptidoglycan synthesis during growth and biofilm formation
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 signaling molecule nitric oxide. We therefore hypothesized treatment with exogenous D-methionine would impact 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 highlights the potential of D-methionine as an adjunctive therapeutic approach for NTHi biofilm-associated infections.
1350-0872
1093-1104
Dawe, Harriet
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Berger, Evelin
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Sihlbom, Carina
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Angus, Elizabeth M.
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Howlin, Robert P.
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Laver, Jay R.
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Tebruegge, Marc
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Hall-Stoodley, Luanne
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Stoodley, Paul
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Faust, Saul N.
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Allan, Raymond N.
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Dawe, Harriet
77249a74-d241-45ad-bb5a-3b20fe3a501f
Berger, Evelin
20d44179-4b01-488f-81b7-5091043d1ece
Sihlbom, Carina
5d23868a-e811-46f6-828b-c0362b0e25b1
Angus, Elizabeth M.
a911c031-be90-4f89-9c65-405df5afb28f
Howlin, Robert P.
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Laver, Jay R.
b2996398-2ccf-40f0-92b8-f338f3de796b
Tebruegge, Marc
2c3dff22-0b5f-48a7-bb36-ce323705f74a
Hall-Stoodley, Luanne
94ebdc00-b549-4488-b15f-5310fb965f5b
Stoodley, Paul
08614665-92a9-4466-806e-20c6daeb483f
Faust, Saul N.
f97df780-9f9b-418e-b349-7adf63e150c1
Allan, Raymond N.
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Dawe, Harriet, Berger, Evelin, Sihlbom, Carina, Angus, Elizabeth M., Howlin, Robert P., Laver, Jay R., Tebruegge, Marc, Hall-Stoodley, Luanne, Stoodley, Paul, Faust, Saul N. and Allan, Raymond N. (2017) D-methionine interferes with non-typeable Haemophilus influenzae peptidoglycan synthesis during growth and biofilm formation. Microbiology (United Kingdom), 163, 1093-1104. (doi:10.1099/mic.0.000491).

Record type: Article

Abstract

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 signaling molecule nitric oxide. We therefore hypothesized treatment with exogenous D-methionine would impact 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 highlights the potential of D-methionine as an adjunctive therapeutic approach for NTHi biofilm-associated infections.

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Accepted/In Press date: 26 May 2017
e-pub ahead of print date: 12 July 2017
Published date: July 2017

Identifiers

Local EPrints ID: 412374
URI: https://eprints.soton.ac.uk/id/eprint/412374
ISSN: 1350-0872
PURE UUID: 5b5f9948-6f19-4d41-aeca-4fca0160bb64
ORCID for Paul Stoodley: ORCID iD orcid.org/0000-0001-6069-273X
ORCID for Saul N. Faust: ORCID iD orcid.org/0000-0003-3410-7642

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Date deposited: 17 Jul 2017 13:33
Last modified: 12 Nov 2019 06:02

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Contributors

Author: Harriet Dawe
Author: Evelin Berger
Author: Carina Sihlbom
Author: Elizabeth M. Angus
Author: Robert P. Howlin
Author: Jay R. Laver
Author: Marc Tebruegge
Author: Luanne Hall-Stoodley
Author: Paul Stoodley ORCID iD
Author: Saul N. Faust ORCID iD
Author: Raymond N. Allan

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