title: A bacterial regulatory RNA attenuates virulence, spread and human host cell phagocytosis.
abstract: Staphylococcus aureus pathogenesis is directed by regulatory proteins and RNAs. We report the case of an RNA attenuating virulence and host uptake, possibly to sustain commensalism. A S. aureus sRNA, SprC (srn_3610), reduced virulence and bacterial loads in a mouse infection model. S. aureus deleted for sprC became more virulent and increased bacterial dissemination in colonized animals. Conversely, inducing SprC expression lowered virulence and the bacterial load. Without sprC, S. aureus phagocytosis by monocytes and macrophages was higher, whereas bacteria were internalized at lower yields when SprC expression was stimulated. Without sprC, higher internalization led to a greater number of extracellular bacteria, facilitating colonization. SprC expression decreased after phagocytosis, concurring with the facilitated growth of bacteria lacking the sRNA in the presence of an oxidant. The major staphylococcal autolysin facilitates S. aureus uptake by human phagocytes. ATL proved to be negatively regulated by SprC. The SprC domains involved in pairing with atl mRNA were analyzed. The addition of ATL reduced phagocytosis of bacteria lacking sprC with no effects on wild-type bacterial uptake, implying that SprC influences phagocytosis, at least in part, by controlling ATL. Since the control of SprC on ATL was modest, other factors must contribute to atl regulation.
authors.affiliation: Inserm U835-Upres EA2311, Biochimie Pharmaceutique, Rennes University, 2 av. du prof. Léon Bernard, 35000 Rennes, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Le Pabic
authors.affiliation: Inserm U835-Upres EA2311, Biochimie Pharmaceutique, Rennes University, 2 av. du prof. Léon Bernard, 35000 Rennes, France.
authors.forename: Noëlla
authors.initials: N
authors.lastname: Germain-Amiot
authors.affiliation: Inserm U835-Upres EA2311, Biochimie Pharmaceutique, Rennes University, 2 av. du prof. Léon Bernard, 35000 Rennes, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Bordeau
authors.affiliation: Inserm U835-Upres EA2311, Biochimie Pharmaceutique, Rennes University, 2 av. du prof. Léon Bernard, 35000 Rennes, France bFelden@univ-rennes1.fr.
authors.forename: Brice
authors.initials: B
authors.lastname: Felden
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D051379:Mice; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D010586:Phagocytes / Q000382:microbiology; D010587:Phagocytosis; D012329:RNA, Bacterial / Q000378:metabolism*; D012333:RNA, Messenger / Q000737:chemistry; D058727:RNA, Small Untranslated / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D012329:RNA, Bacterial; D012333:RNA, Messenger; D058727:RNA, Small Untranslated; D009238:N-Acetylmuramoyl-L-alanine Amidase