CtaM Is Required for Menaquinol Oxidase <italic toggle="yes">aa</italic><sub>3</sub> Function in <named-content content-type="genus-species">Staphylococcus aureus</named-content>

ABSTRACT Staphylococcus aureus is the leading cause of skin and soft tissue infections, bacteremia, osteomyelitis, and endocarditis in the developed world. The ability of S. aureus to cause substantial disease in distinct host environments is supported by a flexible metabolism that allows this patho...

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Autores principales:	Neal D. Hammer, Lici A. Schurig-Briccio, Svetlana Y. Gerdes, Robert B. Gennis, Eric P. Skaar
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1c3c216c3ccb43029f1afd6a604f5e46
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spelling	oai:doaj.org-article:1c3c216c3ccb43029f1afd6a604f5e462021-11-15T15:50:18ZCtaM Is Required for Menaquinol Oxidase <italic toggle="yes">aa</italic><sub>3</sub> Function in <named-content content-type="genus-species">Staphylococcus aureus</named-content>10.1128/mBio.00823-162150-7511https://doaj.org/article/1c3c216c3ccb43029f1afd6a604f5e462016-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00823-16https://doaj.org/toc/2150-7511ABSTRACT Staphylococcus aureus is the leading cause of skin and soft tissue infections, bacteremia, osteomyelitis, and endocarditis in the developed world. The ability of S. aureus to cause substantial disease in distinct host environments is supported by a flexible metabolism that allows this pathogen to overcome challenges unique to each host organ. One feature of staphylococcal metabolic flexibility is a branched aerobic respiratory chain composed of multiple terminal oxidases. Whereas previous biochemical and spectroscopic studies reported the presence of three different respiratory oxygen reductases (o type, bd type, and aa3 type), the genome contains genes encoding only two respiratory oxygen reductases, cydAB and qoxABCD. Previous investigation showed that cydAB and qoxABCD are required to colonize specific host organs, the murine heart and liver, respectively. This work seeks to clarify the relationship between the genetic studies showing the unique roles of the cydAB and qoxABCD in virulence and the respiratory reductases reported in the literature. We establish that QoxABCD is an aa3-type menaquinol oxidase but that this enzyme is promiscuous in that it can assemble as a bo3-type menaquinol oxidase. However, the bo3 form of QoxABCD restricts the carbon sources that can support the growth of S. aureus. In addition, QoxABCD function is supported by a previously uncharacterized protein, which we have named CtaM, that is conserved in aerobically respiring Firmicutes. In total, these studies establish the heme A biosynthesis pathway in S. aureus, determine that QoxABCD is a type aa3 menaquinol oxidase, and reveal CtaM as a new protein required for type aa3 menaquinol oxidase function in multiple bacterial genera. IMPORTANCE Staphylococcus aureus relies upon the function of two terminal oxidases, CydAB and QoxABCD, to aerobically respire and colonize distinct host tissues. Previous biochemical studies support the conclusion that a third terminal oxidase is also present. We establish the components of the S. aureus electron transport chain by determining the heme cofactors that interact with QoxABCD. This insight explains previous observations by revealing that QoxABCD can utilize different heme cofactors and confirms that the electron transport chain of S. aureus is comprised of two terminal menaquinol oxidases. In addition, a newly identified protein, CtaM, is found to be required for the function of QoxABCD. These results provide a more complete assessment of the molecular mechanisms that support staphylococcal respiration.Neal D. HammerLici A. Schurig-BriccioSvetlana Y. GerdesRobert B. GennisEric P. SkaarAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 4 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Neal D. Hammer Lici A. Schurig-Briccio Svetlana Y. Gerdes Robert B. Gennis Eric P. Skaar CtaM Is Required for Menaquinol Oxidase <italic toggle="yes">aa</italic><sub>3</sub> Function in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
description	ABSTRACT Staphylococcus aureus is the leading cause of skin and soft tissue infections, bacteremia, osteomyelitis, and endocarditis in the developed world. The ability of S. aureus to cause substantial disease in distinct host environments is supported by a flexible metabolism that allows this pathogen to overcome challenges unique to each host organ. One feature of staphylococcal metabolic flexibility is a branched aerobic respiratory chain composed of multiple terminal oxidases. Whereas previous biochemical and spectroscopic studies reported the presence of three different respiratory oxygen reductases (o type, bd type, and aa3 type), the genome contains genes encoding only two respiratory oxygen reductases, cydAB and qoxABCD. Previous investigation showed that cydAB and qoxABCD are required to colonize specific host organs, the murine heart and liver, respectively. This work seeks to clarify the relationship between the genetic studies showing the unique roles of the cydAB and qoxABCD in virulence and the respiratory reductases reported in the literature. We establish that QoxABCD is an aa3-type menaquinol oxidase but that this enzyme is promiscuous in that it can assemble as a bo3-type menaquinol oxidase. However, the bo3 form of QoxABCD restricts the carbon sources that can support the growth of S. aureus. In addition, QoxABCD function is supported by a previously uncharacterized protein, which we have named CtaM, that is conserved in aerobically respiring Firmicutes. In total, these studies establish the heme A biosynthesis pathway in S. aureus, determine that QoxABCD is a type aa3 menaquinol oxidase, and reveal CtaM as a new protein required for type aa3 menaquinol oxidase function in multiple bacterial genera. IMPORTANCE Staphylococcus aureus relies upon the function of two terminal oxidases, CydAB and QoxABCD, to aerobically respire and colonize distinct host tissues. Previous biochemical studies support the conclusion that a third terminal oxidase is also present. We establish the components of the S. aureus electron transport chain by determining the heme cofactors that interact with QoxABCD. This insight explains previous observations by revealing that QoxABCD can utilize different heme cofactors and confirms that the electron transport chain of S. aureus is comprised of two terminal menaquinol oxidases. In addition, a newly identified protein, CtaM, is found to be required for the function of QoxABCD. These results provide a more complete assessment of the molecular mechanisms that support staphylococcal respiration.
format	article
author	Neal D. Hammer Lici A. Schurig-Briccio Svetlana Y. Gerdes Robert B. Gennis Eric P. Skaar
author_facet	Neal D. Hammer Lici A. Schurig-Briccio Svetlana Y. Gerdes Robert B. Gennis Eric P. Skaar
author_sort	Neal D. Hammer
title	CtaM Is Required for Menaquinol Oxidase <italic toggle="yes">aa</italic><sub>3</sub> Function in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_short	CtaM Is Required for Menaquinol Oxidase <italic toggle="yes">aa</italic><sub>3</sub> Function in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_full	CtaM Is Required for Menaquinol Oxidase <italic toggle="yes">aa</italic><sub>3</sub> Function in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_fullStr	CtaM Is Required for Menaquinol Oxidase <italic toggle="yes">aa</italic><sub>3</sub> Function in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_full_unstemmed	CtaM Is Required for Menaquinol Oxidase <italic toggle="yes">aa</italic><sub>3</sub> Function in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_sort	ctam is required for menaquinol oxidase <italic toggle="yes">aa</italic><sub>3</sub> function in <named-content content-type="genus-species">staphylococcus aureus</named-content>
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/1c3c216c3ccb43029f1afd6a604f5e46
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CtaM Is Required for Menaquinol Oxidase <italic toggle="yes">aa</italic><sub>3</sub> Function in <named-content content-type="genus-species">Staphylococcus aureus</named-content>

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