Maturation of molybdoenzymes and its influence on the pathogenesis of non-typeable Haemophilus influenzae

Dhouib, R; Pg Othman, DSM; Essilfie, AT; Hansbro, PM; Hanson, JO; McEwan, AG; Kappler, U

Maturation of molybdoenzymes and its influence on the pathogenesis of non-typeable Haemophilus influenzae

Dhouib, R Pg Othman, DSM Essilfie, AT Hansbro, PM

Hanson, JO McEwan, AG Kappler, U

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Publication Type:: Journal Article
Citation:: Frontiers in Microbiology, 2015, 6 (NOV)
Issue Date:: 2015-01-01

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Field	Value	Language
dc.contributor.author	Dhouib, R	en_US
dc.contributor.author	Pg Othman, DSM	en_US
dc.contributor.author	Essilfie, AT	en_US
dc.contributor.author	Hansbro, PM https://orcid.org/0000-0002-4741-3035	en_US
dc.contributor.author	Hanson, JO	en_US
dc.contributor.author	McEwan, AG	en_US
dc.contributor.author	Kappler, U	en_US
dc.date.available	2015-10-19	en_US
dc.date.issued	2015-01-01	en_US
dc.identifier.citation	Frontiers in Microbiology, 2015, 6 (NOV)	en_US
dc.identifier.uri	http://hdl.handle.net/10453/128817
dc.description.abstract	© 2015 Dhouib, Pg Othman, Essilfie, Hansbro, Hanson, McEwan and Kappler. Mononuclear molybdenum enzymes of the dimethylsulfoxide (DMSO) reductase family occur exclusively in prokaryotes, and a loss of some these enzymes has been linked to a loss of bacterial virulence in several cases. The MobA protein catalyzes the final step in the synthesis of the molybdenum guanine dinucleotide (MGD) cofactor that is exclusive to enzymes of the DMSO reductase family. MobA has been proposed as a potential target for control of virulence since its inhibition would affect the activities of all molybdoenzymes dependent upon MGD. Here, we have studied the phenotype of a mobA mutant of the host-adapted human pathogen Haemophilus influenzae. H. influenzae causes and contributes to a variety of acute and chronic diseases of the respiratory tract, and several enzymes of the DMSO reductase family are conserved and highly expressed in this bacterium. The mobA mutation caused a significant decrease in the activities of all Mo-enzymes present, and also resulted in a small defect in anaerobic growth. However, we did not detect a defect in in vitro biofilm formation nor in invasion and adherence to human epithelial cells in tissue culture compared to the wild-type. In a murine in vivo model, the mobA mutant showed only a mild attenuation compared to the wild-type. In summary, our data show that MobA is essential for the activities of molybdenum enzymes, but does not appear to affect the fitness of H. influenzae. These results suggest that MobA is unlikely to be a useful target for antimicrobials, at least for the purpose of treating H. influenzae infections.	en_US
dc.relation.ispartof	Frontiers in Microbiology	en_US
dc.relation.isbasedon	10.3389/fmicb.2015.01219	en_US
dc.title	Maturation of molybdoenzymes and its influence on the pathogenesis of non-typeable Haemophilus influenzae	en_US
dc.type	Journal Article
utslib.citation.volume	NOV	en_US
utslib.citation.volume	6	en_US
utslib.for	0502 Environmental Science and Management	en_US
utslib.for	0503 Soil Sciences	en_US
utslib.for	0605 Microbiology	en_US
pubs.embargo.period	Not known	en_US
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.issue	NOV	en_US
pubs.publication-status	Published	en_US
pubs.volume	6	en_US

Abstract:

© 2015 Dhouib, Pg Othman, Essilfie, Hansbro, Hanson, McEwan and Kappler. Mononuclear molybdenum enzymes of the dimethylsulfoxide (DMSO) reductase family occur exclusively in prokaryotes, and a loss of some these enzymes has been linked to a loss of bacterial virulence in several cases. The MobA protein catalyzes the final step in the synthesis of the molybdenum guanine dinucleotide (MGD) cofactor that is exclusive to enzymes of the DMSO reductase family. MobA has been proposed as a potential target for control of virulence since its inhibition would affect the activities of all molybdoenzymes dependent upon MGD. Here, we have studied the phenotype of a mobA mutant of the host-adapted human pathogen Haemophilus influenzae. H. influenzae causes and contributes to a variety of acute and chronic diseases of the respiratory tract, and several enzymes of the DMSO reductase family are conserved and highly expressed in this bacterium. The mobA mutation caused a significant decrease in the activities of all Mo-enzymes present, and also resulted in a small defect in anaerobic growth. However, we did not detect a defect in in vitro biofilm formation nor in invasion and adherence to human epithelial cells in tissue culture compared to the wild-type. In a murine in vivo model, the mobA mutant showed only a mild attenuation compared to the wild-type. In summary, our data show that MobA is essential for the activities of molybdenum enzymes, but does not appear to affect the fitness of H. influenzae. These results suggest that MobA is unlikely to be a useful target for antimicrobials, at least for the purpose of treating H. influenzae infections.

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http://hdl.handle.net/10453/128817