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Streptococcus agalactiae or Group B Streptococcus (GBS) is a human commensal bacterium that can become a pathogen. In addition to direct effects of virulence factors, active aerobic respiratory metabolism has a role in the GBS infection process. GBS encodes a CydA CydB cytochrome bd quinol oxidase for respiration, which is activated by exogenously heme and (demethyl)menaquinone. Respiratory metabolism decreases oxidative and acid stress from the environment, improves long-term survival of GBS and contributes to its virulence. GBS possess a homolog of the MenA 1,4-dihydroxy-2-naphthoate prenyltransferase enzyme, involved in the synthesis of menaquinone. Furthermore, GBS encodes an ispB gene (gbs1783) involved in the synthesis of isoprenoid chains. In the presence of DHNA, we showed that GBS is able to synthesize long chain demethylmenaquinones (DMK-10) that are cofactors of the CydA CydB terminal oxidase that also requires exogenous heme to be active (Franza et al., 2016). We also showed that the type 2 NADH dehydrogenase has an essential role in respiration and contributes to S. agalactiae virulence (Lencina et al. 2018). The Rex transcriptional regulator is involved in the control of the NAD⁺/NADH intracellular ratio and plays a role in the pathogenicity of GBS (Franza et al., 2021). We showed that GBS is able to use the DHNA metabolite produced by E. coli in coculture. We are now working on the characterization of the molecular mechanisms involved in this nutritional exchange.

Key words: Streptococcus agalactiae, respiratory metabolism, menaquinone synthesis, NADH dehydrogenase, cytochrome bd oxidase, DHNA (1,4-dihydroxy-2-naphthoic acid), crossfeeding , Rex transcription repressor, regulation.

Bibliography (2015-2018):

- Franza, T., Delavenne, E., Derré-Bobillot, A., Juillard, V., Boulay, M., Demey, E., Vinh, J., Lamberet, G., Gaudu, P. (2016). A partial metabolic pathway enables group b streptococcus to overcome quinone deficiency in a host bacterial community. Molecular Microbiology, 102 (1), 81-91

- Lencina A. M., Franza T., Sullivan M. J., Ulett G. C., Ipe D. S., Gaudu P., Gennis R. B., Schurig-Briccio L. A. (2018). Type 2 NADH dehydrogenase is the only point of entry for electrons into the Streptococcus agalactiae respiratory chain and is a potential drug target. mBio, 9 (4), https://dx.doi.org/10.1128/mBio.01034-18, https://hal.inrae.fr/hal-02621541

- Franza T., Rogstam A., Thiyagarajan S., Sullivan M., Derré-Bobillot A., Bauer M., Goh K., Da Cunha V., Glaser P., Logan D., Ulett G., von Wachenfeldt C., Gaudu P. (2021). NAD⁺ pool depletion as a signal for the Rex regulon involved in Streptococcus agalactiae virulence. PLoS Pathogens, 17 (8), e1009791, https://dx.doi.org/10.1371/journal.ppat.1009791, https://hal.inrae.fr/hal-03319837

- Franza, T., and Gaudu, P. (2022). Quinones: More Than Electron Shuttles. Research in microbiology, Volume 173,  Issues 6–7, p 103953,

Collaborations:

- JP Nougayrède from the Team Pathogénie et Commensalisme des Entérobactéries de l’Institut de Recherche en Santé Digestive (IRSD, UMR 1220, Toulouse France).

- R Gennis from the Department of Biochemistry (University of Illinois, USA).

- GC Ulett (Griffith University, Australia). C. von Wachenfeldt (University of Lund, Sweden).