The University of Southampton
University of Southampton Institutional Repository

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
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.
f3c84990-6196-47d4-ad8a-80954ea46c7f
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.
390a7d0a-38e1-410a-8dfe-c8ef8408f5e1
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.
f3c84990-6196-47d4-ad8a-80954ea46c7f
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.
390a7d0a-38e1-410a-8dfe-c8ef8408f5e1

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, 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.

Text
Microbiology Manuscript - Accepted Manuscript
Download (106kB)

More information

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: http://eprints.soton.ac.uk/id/eprint/412374
ISSN: 1350-0872
PURE UUID: 5b5f9948-6f19-4d41-aeca-4fca0160bb64
ORCID for Jay R. Laver: ORCID iD orcid.org/0000-0003-3314-5989
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

Catalogue record

Date deposited: 17 Jul 2017 13:33
Last modified: 16 Mar 2024 05:23

Export record

Altmetrics

Contributors

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

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×