Nosocomial Transmission of Necrotizing Fasciitis: A Molecular Characterization of Group A Streptococcal DNases in Clinical Virulence.
Geoffrey Deneubourg, Lionel Schiavolin, Dalila Lakhloufi, Gwenaelle Botquin, Valérie Delforge, Mark R Davies, Pierre R Smeesters, Anne Botteaux
Author Information
Geoffrey Deneubourg: Molecular Bacteriology, European Plotkin Institute for Vaccinology (EPIV), Université Libre de Bruxelles, 1070 Bruxelles, Belgium.
Lionel Schiavolin: Molecular Bacteriology, European Plotkin Institute for Vaccinology (EPIV), Université Libre de Bruxelles, 1070 Bruxelles, Belgium. ORCID
Dalila Lakhloufi: Molecular Bacteriology, European Plotkin Institute for Vaccinology (EPIV), Université Libre de Bruxelles, 1070 Bruxelles, Belgium.
Gwenaelle Botquin: Molecular Bacteriology, European Plotkin Institute for Vaccinology (EPIV), Université Libre de Bruxelles, 1070 Bruxelles, Belgium.
Valérie Delforge: Molecular Bacteriology, European Plotkin Institute for Vaccinology (EPIV), Université Libre de Bruxelles, 1070 Bruxelles, Belgium.
Mark R Davies: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia. ORCID
Pierre R Smeesters: Molecular Bacteriology, European Plotkin Institute for Vaccinology (EPIV), Université Libre de Bruxelles, 1070 Bruxelles, Belgium.
Anne Botteaux: Molecular Bacteriology, European Plotkin Institute for Vaccinology (EPIV), Université Libre de Bruxelles, 1070 Bruxelles, Belgium. ORCID
, or Group A (GAS), is responsible for over 500,000 deaths per year. Approximately 15% of these deaths are caused by necrotizing soft-tissue infections. In 2008, we isolated an M5 GAS, named the LO1 strain, responsible for the nosocomial transmission of necrotizing fasciitis between a baby and a nurse in Belgium. To understand this unusual transmission route, the LO1 strain was sequenced. A comparison of the LO1 genome and transcriptome with the reference M5 Manfredo strain was conducted. We found that the major differences were the presence of an additional DNase and a Tn916-like transposon in the LO1 and other invasive M5 genomes. RNA-seq analysis showed that genes present on the transposon were barely expressed. In contrast, the DNases presented different expression profiles depending on the tested conditions. We generated knock-out mutants in the LO1 background and characterized their virulence phenotype. We also determined their nuclease activity on different substrates. We found that DNases are dispensable for biofilm formation and adhesion to both keratinocytes and pharyngeal cells. Three of these were found to be essential for blood survival; Spd4 and Sdn are implicated in phagocytosis resistance, and Spd1 is responsible for neutrophil extracellular trap (NET) degradation.
