The DmsABC Sulfoxide Reductase Supports Virulence in Non-typeable Haemophilus influenzae.

Dhouib, R; Nasreen, M; Othman, DSMP; Ellis, D; Lee, S; Essilfie, A-T; Hansbro, PM; McEwan, AG; Kappler, U

The DmsABC Sulfoxide Reductase Supports Virulence in Non-typeable Haemophilus influenzae.

Dhouib, R Nasreen, M Othman, DSMP Ellis, D Lee, S Essilfie, A-T Hansbro, PM McEwan, AG Kappler, U

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Publisher:: Frontiers Media
Publication Type:: Journal Article
Citation:: Frontiers in Microbiology, 2021, 12, pp. 1-11
Issue Date:: 2021

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Field	Value	Language
dc.contributor.author	Dhouib, R
dc.contributor.author	Nasreen, M
dc.contributor.author	Othman, DSMP
dc.contributor.author	Ellis, D
dc.contributor.author	Lee, S
dc.contributor.author	Essilfie, A-T
dc.contributor.author	Hansbro, PM
dc.contributor.author	McEwan, AG
dc.contributor.author	Kappler, U
dc.date.accessioned	2022-02-14T21:58:46Z
dc.date.available	2021-06-21
dc.date.available	2022-02-14T21:58:46Z
dc.date.issued	2021
dc.identifier.citation	Frontiers in Microbiology, 2021, 12, pp. 1-11
dc.identifier.issn	1664-302X
dc.identifier.issn	1664-302X
dc.identifier.uri	http://hdl.handle.net/10453/154509
dc.description.abstract	Although molybdenum-containing enzymes are well-established as having a key role in bacterial respiration, it is increasingly recognized that some may also support bacterial virulence. Here, we show that DmsABC, a putative dimethylsulfoxide (DMSO) reductase, is required for fitness of the respiratory pathogen Haemophilus influenzae (Hi) in different models of infection. Expression of the dmsABC operon increased with decreasing oxygen availability, but despite this, a Hi2019Δd msA strain did not show any defects in anaerobic growth on chemically defined medium (CDM), and viability was also unaffected. Although Hi2019Δd msA exhibited increased biofilm formation in vitro and greater resistance to hypochlorite killing compared to the isogenic wild-type strain, its survival in contact with primary human neutrophils, in infections of cultured tissue cells, or in a mouse model of lung infection was reduced compared to Hi2019WT. The tissue cell infection model revealed a two-fold decrease in intracellular survival, while in the mouse model of lung infection Hi2019Δd msA was strongly attenuated and below detection levels at 48 h post-inoculation. While Hi2019WT was recovered in approximately equal numbers from bronchoalveolar lavage fluid (BALF) and lung tissue, survival of Hi2019Δd msA was reduced in lung tissue compared to BALF samples, indicating that Hi2019Δd msA had reduced access to or survival in the intracellular niche. Our data clearly indicate for the first time a role for DmsABC in H. influenzae infection and that the conditions under which DmsABC is required in this bacterium are closely linked to interactions with the host.
dc.format	Electronic-eCollection
dc.language	eng
dc.publisher	Frontiers Media
dc.relation.ispartof	Frontiers in Microbiology
dc.relation.isbasedon	10.3389/fmicb.2021.686833
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0502 Environmental Science and Management, 0503 Soil Sciences, 0605 Microbiology
dc.title	The DmsABC Sulfoxide Reductase Supports Virulence in Non-typeable Haemophilus influenzae.
dc.type	Journal Article
utslib.citation.volume	12
utslib.location.activity	Switzerland
utslib.for	0502 Environmental Science and Management
utslib.for	0503 Soil Sciences
utslib.for	0605 Microbiology
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2022-02-14T21:58:41Z
pubs.publication-status	Published
pubs.volume	12

Abstract:

Although molybdenum-containing enzymes are well-established as having a key role in bacterial respiration, it is increasingly recognized that some may also support bacterial virulence. Here, we show that DmsABC, a putative dimethylsulfoxide (DMSO) reductase, is required for fitness of the respiratory pathogen Haemophilus influenzae (Hi) in different models of infection. Expression of the dmsABC operon increased with decreasing oxygen availability, but despite this, a Hi2019Δd msA strain did not show any defects in anaerobic growth on chemically defined medium (CDM), and viability was also unaffected. Although Hi2019Δd msA exhibited increased biofilm formation in vitro and greater resistance to hypochlorite killing compared to the isogenic wild-type strain, its survival in contact with primary human neutrophils, in infections of cultured tissue cells, or in a mouse model of lung infection was reduced compared to Hi2019WT. The tissue cell infection model revealed a two-fold decrease in intracellular survival, while in the mouse model of lung infection Hi2019Δd msA was strongly attenuated and below detection levels at 48 h post-inoculation. While Hi2019WT was recovered in approximately equal numbers from bronchoalveolar lavage fluid (BALF) and lung tissue, survival of Hi2019Δd msA was reduced in lung tissue compared to BALF samples, indicating that Hi2019Δd msA had reduced access to or survival in the intracellular niche. Our data clearly indicate for the first time a role for DmsABC in H. influenzae infection and that the conditions under which DmsABC is required in this bacterium are closely linked to interactions with the host.

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http://hdl.handle.net/10453/154509