title: Visualization of the role of host heme on the virulence of the heme auxotroph Streptococcus agalactiae.
abstract: Heme is essential for several cellular key functions but is also toxic. Whereas most bacterial pathogens utilize heme as a metabolic cofactor and iron source, the impact of host heme during bacterial infection remains elusive. The opportunist pathogen Streptococcus agalactiae does not synthesize heme but still uses it to activate a respiration metabolism. Concomitantly, heme toxicity is mainly controlled by the HrtBA efflux transporter. Here we investigate how S. agalactiae manages heme toxicity versus benefits in the living host. Using bioluminescent bacteria and heme-responsive reporters for in vivo imaging, we show that the capacity of S. agalactiae to overcome heme toxicity is required for successful infection, particularly in blood-rich organs. Host heme is simultaneously required, as visualized by a generalized infection defect of a respiration-negative mutant. In S. agalactiae, HrtBA expression responds to an intracellular heme signal via activation of the two-component system HssRS. A hssRS promoter-driven intracellular luminescent heme sensor was designed to identify host compartments that supply S. agalactiae with heme. S. agalactiae acquires heme in heart, kidneys, and liver, but not in the brain. We conclude that S. agalactiae response to heme is organ-dependent, and its efflux may be particularly relevant in late stages of infection.
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy en Josas, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Joubert
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy en Josas, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Dagieu
authors.affiliation: Fromagerie BEL, 7 boulevard de l'Industrie, 41100 Vendôme, France.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Fernandez
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy en Josas, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Derré-Bobillot
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy en Josas, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Borezée-Durant
authors.affiliation: Unité ISP, INRA, 37380 Nouzilly, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fleurot
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy en Josas, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gruss
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy en Josas, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Lechardeur
mesh_terms: D000332:Aerobiosis / Q000187:drug effects; D000818:Animals; D005798:Genes, Bacterial; D006418:Heme / Q000378:metabolism* / Q000633:toxicity; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D013290:Streptococcal Infections / Q000382:microbiology / Q000473:pathology; D013292:Streptococcus agalactiae / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity*; D014774:Virulence / Q000187:drug effects
chemical_list: D006418:Heme