title: Role of the (Mn)superoxide dismutase of Enterococcus faecalis in the in vitro interaction with microglia.
abstract: Enterococcus faecalis is a significant human pathogen worldwide and is responsible for severe nosocomial and community-acquired infections. Although enterococcal meningitis is rare, mortality is considerable, reaching 21 %. Nevertheless, the pathogenetic mechanisms of this infection remain poorly understood, even though the ability of E. faecalis to avoid or survive phagocytic attack in vivo may be very important during the infection process. We previously showed that the manganese-cofactored superoxide dismutase (MnSOD) SodA of E. faecalis was implicated in oxidative stress responses and, interestingly, in the survival within mouse peritoneal macrophages using an in vivo-in vitro infection model. In the present study, we investigated the role of MnSOD in the interaction of E. faecalis with microglia, the brain-resident macrophages. By using an in vitro infection model, murine microglial cells were challenged in parallel with the wild-type strain JH2-2 and its isogenic sodA deletion mutant. While both strains were phagocytosed by microglia efficiently and to a similar extent, the ΔsodA mutant was found to be significantly more susceptible to microglial killing than JH2-2, as assessed by the antimicrobial protection assay. In addition, a significantly higher percentage of acidic ΔsodA-containing phagosomes was found and these also underwent enhanced maturation as determined by the expression of endolysosomal markers. In conclusion, these results show that the MnSOD of E. faecalis contributes to survival of the bacterium in microglial cells by influencing their antimicrobial activity, and this could even be important for intracellular killing in neutrophils and thus for E. faecalis pathogenesis.
authors.affiliation: Dipartimento di Scienze di Sanità Pubblica, Università degli Studi di Modena e Reggio Emilia, Via Campi 287, 41125 Modena, Italy.
authors.forename: Samuele
authors.initials: S
authors.lastname: Peppoloni
authors.affiliation: Institute of Microbiology, Catholic University of the Sacred Heart, 00168 Rome, Italy.
authors.forename: Brunella
authors.initials: B
authors.lastname: Posteraro
authors.affiliation: Dipartimento di Scienze di Sanità Pubblica, Università degli Studi di Modena e Reggio Emilia, Via Campi 287, 41125 Modena, Italy.
authors.forename: Bruna
authors.initials: B
authors.lastname: Colombari
authors.affiliation: Dipartimento di Scienze di Sanità Pubblica, Università degli Studi di Modena e Reggio Emilia, Via Campi 287, 41125 Modena, Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Manca
authors.affiliation: Laboratoire de Microbiologie de l'Environnement, EA 956 USC INRA, IRBA, Université de Caen, 14032 Caen Cedex, France.
authors.forename: Axel
authors.initials: A
authors.lastname: Hartke
authors.affiliation: Laboratoire de Microbiologie de l'Environnement, EA 956 USC INRA, IRBA, Université de Caen, 14032 Caen Cedex, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Giard
authors.affiliation: Institute of Microbiology, Catholic University of the Sacred Heart, 00168 Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sanguinetti
authors.affiliation: Institute of Microbiology, Catholic University of the Sacred Heart, 00168 Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fadda
authors.affiliation: Dipartimento ad Attività Integrata di Laboratori, Anatomia Patologica e Medicina Legale, Azienda Ospedaliero-Universitaria di Modena, Via del Pozzo no 71, 41124 Modena, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Blasi
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D013293:Enterococcus faecalis / Q000201:enzymology* / Q000472:pathogenicity*; D017353:Gene Deletion; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D010587:Phagocytosis; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; C095500:SodA protein, Bacteria; D013482:Superoxide Dismutase