title: Dormant bacteria within Staphylococcus epidermidis biofilms have low inflammatory properties and maintain tolerance to vancomycin and penicillin after entering planktonic growth.
abstract: Staphylococcus epidermidis is the most commonly isolated aetiological agent of nosocomial infections, mainly due to its ability to establish biofilms on indwelling medical devices. Detachment of bacteria from S. epidermidis biofilms and subsequent growth in the planktonic form is a hallmark of the pathogenesis of these infections leading to dissemination. Here we showed that S. epidermidis cells collected from biofilms cultured in conditions that promote cell viability present marked changes in their physiological status upon initiating a planktonic mode of growth. When compared to cells growing in biofilms, they displayed an increased SYBR green I staining intensity, increased transcription of the rpiA gene, decreased transcription of the icaA gene, as well as higher susceptibility to vancomycin and penicillin. When bacteria collected from biofilms with high proportions of dormant cells were subsequently cultured in the planktonic mode, a large proportion of cells maintained a low SYBR green I staining intensity and increased resistance to vancomycin and penicillin, a profile typical of dormant cells. This phenotype further associated with a decreased ability of these biofilm-derived cells to induce the production of pro-inflammatory cytokines by bone marrow-derived dendritic cells in vitro. These results demonstrated that cells detached from the biofilm maintain a dormant cell-like phenotype, having a low pro-inflammatory effect and decreased susceptibility to antibiotics, suggesting these cells may contribute to the recalcitrant nature of biofilm infections.
authors: IBMC - Instituto de Biologia Molecular e Celular, Rua do Campo Alegre 83, Porto, Portugal.|ICBAS-UP - Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto, Rua de Jorge Viterbo Ferreira no. 228, 4050-313, Porto, Portugal.
authors: Filipe
authors: F
authors: Cerca
authors: CEB, Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal.
authors: Ângela
authors: Â
authors: França
authors: IBMC - Instituto de Biologia Molecular e Celular, Rua do Campo Alegre 83, Porto, Portugal.
authors: Begoña
authors: B
authors: Pérez-Cabezas
authors: CEB, Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal.|ICBAS-UP - Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto, Rua de Jorge Viterbo Ferreira no. 228, 4050-313, Porto, Portugal.
authors: Virgínia
authors: V
authors: Carvalhais
authors: IBMC - Instituto de Biologia Molecular e Celular, Rua do Campo Alegre 83, Porto, Portugal.|ICBAS-UP - Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto, Rua de Jorge Viterbo Ferreira no. 228, 4050-313, Porto, Portugal.
authors: Adília
authors: A
authors: Ribeiro
authors: CEB, Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal.
authors: Joana
authors: J
authors: Azeredo
authors: Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA 02115, USA.
authors: Gerald
authors: G
authors: Pier
authors: CEB, Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal.
authors: Nuno
authors: N
authors: Cerca
authors: IBMC - Instituto de Biologia Molecular e Celular, Rua do Campo Alegre 83, Porto, Portugal.|ICBAS-UP - Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto, Rua de Jorge Viterbo Ferreira no. 228, 4050-313, Porto, Portugal.
authors: Manuel
authors: M
authors: Vilanova
mesh_terms: D000818:Animals; D018441:Biofilms / Q000254:growth & development*; D016207:Cytokines / Q000378:metabolism; D004361:Drug Tolerance; D020869:Gene Expression Profiling; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000382:microbiology; D008807:Mice, Inbred BALB C; D010406:Penicillins / Q000494:pharmacology*; D013212:Staphylococcus epidermidis / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology / Q000502:physiology*; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D010406:Penicillins; D014640:Vancomycin