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NAD+ pool depletion...
NAD+ pool depletion as a signal for the Rex regulon involved in Streptococcus agalactiae virulence
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- Franza, Thierry (författare)
- University of Paris-Saclay
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- Rogstam, Annika (författare)
- Lund University,Lunds universitet,Molekylär cellbiologi,Biologiska institutionen,Naturvetenskapliga fakulteten,Molecular Cell Biology,Department of Biology,Faculty of Science
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- Thiyagarajan, Saravanamuthu (författare)
- Skåne University Hospital
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- Sullivan, Matthew J. (författare)
- Griffith University
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- Derré-Bobillot, Aurelie (författare)
- University of Paris-Saclay
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- Bauer, Mikael C. (författare)
- Lund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Goh, Kelvin G.K. (författare)
- Griffith University
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- Cunha, Violette Da (författare)
- Centre d'Ecologie Fonctionnelle et Evolutive (CEFE)
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- Glaser, Philippe (författare)
- Pasteur Institute
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- Logan, Derek T. (författare)
- Lund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Ulett, Glen C. (författare)
- Griffith University
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- von Wachenfeldt, Claes (författare)
- Lund University,Lunds universitet,Molekylär cellbiologi,Biologiska institutionen,Naturvetenskapliga fakulteten,Mikrobiologigruppen,Forskargrupper vid Lunds universitet,Molecular Cell Biology,Department of Biology,Faculty of Science,Microbiology Group,Lund University Research Groups
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- Gaudu, Philippe (författare)
- University of Paris-Saclay
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(creator_code:org_t)
- 2021-08-09
- 2021
- Engelska.
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 17:8
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://journals.plo...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- In many Gram-positive bacteria, the redox-sensing transcriptional repressor Rex controls central carbon and energy metabolism by sensing the intra cellular balance between the reduced and oxidized forms of nicotinamide adenine dinucleotide; the NADH/NAD+ ratio. Here, we report high-resolution crystal structures and characterization of a Rex ortholog (Gbs1167) in the opportunistic pathogen, Streptococcus agalactiae, also known as group B streptococcus (GBS). We present structures of Rex bound to NAD+ and to a DNA operator which are the first structures of a Rex-family member from a pathogenic bacterium. The structures reveal the molecular basis of DNA binding and the conformation alterations between the free NAD+ complex and DNA-bound form of Rex. Transcriptomic analysis revealed that GBS Rex controls not only central metabolism, but also expression of the monocistronic rex gene as well as virulence gene expression. Rex enhances GBS virulence after disseminated infection in mice. Mechanistically, NAD+ stabilizes Rex as a repressor in the absence of NADH. However, GBS Rex is unique compared to Rex regulators previously characterized because of its sensing mechanism: we show that it primarily responds to NAD+ levels (or growth rate) rather than to the NADH/NAD+ ratio. These results indicate that Rex plays a key role in GBS pathogenicity by modulating virulence factor gene expression and carbon metabolism to harvest nutrients from the host.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
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Franza, Thierry
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Rogstam, Annika
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Thiyagarajan, Sa ...
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Sullivan, Matthe ...
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Derré-Bobillot, ...
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Bauer, Mikael C.
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visa fler...
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Goh, Kelvin G.K.
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Cunha, Violette ...
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Glaser, Philippe
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Logan, Derek T.
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Ulett, Glen C.
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von Wachenfeldt, ...
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Gaudu, Philippe
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visa färre...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Mikrobiologi ino ...
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PLoS Pathogens
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Lunds universitet