Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive bacterium causing mastitis in dairy cattle and a human commensal colonizing c.a. 30% of healthy adults (gastrointestinal and genitourinary tracts). GBS can cause serious infections, most of which affect pregnant women, newborns and elderly alduts. Our group has demonstrated that, in addition to direct effects of several 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. 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 pool and also plays a role in the pathogenicity of GBS (Franza et al., 2021). We also showed that in the presence of 1,4-dihydroxy-2-naphthoic acid (DHNA) GBS is able to synthesize long chain demethylmenaquinones (DMK-10) that are cofactors for the CydAB terminal oxidase (Franza et al., 2016). We demonstrated that GBS is able to use the DHNA metabolite produced by Escherichia coli in coculture. We are now working on the characterization of the molecular mechanisms involved in this nutritional exchange. This topic is supported by a MICA INRAE funding (CROSS 2022-2023).
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.
Publications:
– 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. hal-02928680v1
– 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. hal-02621541.
– Franza T., Rogstam A., Thiyagarajan S., et al. Gaudu P. (2021). NA 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. hal-03319837v1. – https://sco.lt/8RiU08
– Franza, T., and Gaudu, P. (2022). Quinones: More Than Electron Shuttles. Research in microbiology, Volume 173, Issues 6–7, p 103953. hal-04097622v1
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).
