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Title: Vancomycin-intermediate Staphylococcus aureus isolates are attenuated for virulence when compared with susceptible progenitors.
Austin Authors: Cameron, D R;Lin, Y-H;Trouillet-Assant, S;Tafani, V;Kostoulias, X;Mouhtouris, E ;Skinner, N;Visvanathan, K;Baines, S L;Howden, Benjamin P ;Monk, I R;Laurent, F;Stinear, T P;Peleg, A Y
Affiliation: Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Australia
Department of Microbiology and Immunology, The University of Melbourne at the Doherty Institute of Infection & Immunity, Australia
Department of Microbiology, French National Reference Centre for Staphylococci, Hospices Civils de Lyon, International Centre of Infectiology Research, France
Department of Surgery, The University of Melbourne, Australia
Department of Medicine, The University of Melbourne, Australia
Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia
Department of Microbiology, Austin Health, Heidelberg, Victoria, Australia
Department of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash University, Australia
Issue Date: Oct-2017 2017-04-07
Publication information: Clinical microbiology and infection 2017; 23(10): 767-773
Abstract: Vancomycin-intermediate Staphylococcus aureus (VISA) is associated with genetic changes that may also impact upon pathogenicity. In the current study, we compared the virulence of clinical VISA strains with their isogenic vancomycin-susceptible progenitors (VSSA). Production of the critical virulence protein, α toxin, was assessed using Western blot analysis and was correlated to agr activity using a bioluminescent agr-reporter. Cytotoxicity and intracellular persistence were compared ex vivo for VSSA and VISA within non-professional phagocytes (NPP). Virulence and host immune responses were further explored in vivo using a murine model of bacteraemia. VISA isolates produced up to 20-fold less α toxin compared with VSSA, and this was corroborated by either loss of agr activity due to agr mutation, or altered agr activity in the absence of mutation. VISA were less cytotoxic towards NPP and were associated with enhanced intracellular persistence, suggesting that NPP may act as a reservoir for VISA. Infection with VSSA strains produced higher mortality in a murine bacteraemia model (≥90% 7-day mortality) compared with infection with VISA isolates (20% to 50%, p <0.001). Mice infected with VISA produced a dampened immune response (4.6-fold reduction in interleukin-6, p <0.001) and persistent organ bacterial growth was observed for VISA strains out to 7 days. These findings highlight the remarkable adaptability of S. aureus, whereby, in addition to having reduced antibiotic susceptibility, VISA alter the expression of pathogenic factors to circumvent the host immune response to favour persistent infection over acute virulence.
DOI: 10.1016/j.cmi.2017.03.027
Journal: Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
PubMed URL: 28396035
Type: Journal Article
Subjects: Accessory gene regulator
Staphylococcus aureus
Vancomycin-intermediate Staphylococcus aureus
α toxin
Appears in Collections:Journal articles

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