Impact of sub-inhibitory antibiotics on fibronectin-mediated host cell adhesion and invasion by Staphylococcus aureus

BMC Microbiology

Research Article

Michele Bes¹  François Vandenesch¹  Jerome Etienne¹  Gerard Lina¹  Anne Tristan¹  Frederic Laurent¹  Jean Philippe Rasigade¹  Yannick Lhoste¹  Abdelmalek Moulay¹  Oana Dumitrescu² 

[1] INSERM, U851, 69008, Lyon, France;Centre National de référence des Staphylocoques, Faculté de Médecine Lyon Est, Université de Lyon, 69008, Lyon, France;INSERM, U851, 69008, Lyon, France;Centre National de référence des Staphylocoques, Faculté de Médecine Lyon Est, Université de Lyon, 69008, Lyon, France;Centre National de Référence des Staphylocoques, 7 rue Guillaume Paradin, 6937208, Lyon cedex, France;

关键词: Clindamycin;    Linezolid;    Moxifloxacin;    Oxacillin;    Human Osteoblast;   

DOI  :  10.1186/1471-2180-11-263

 received in 2011-06-13, accepted in 2011-12-14,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundStaphylococcus aureus is a well-armed pathogen prevalent in severe infections such as endocarditis and osteomyelitis. Fibronectin-binding proteins A and B, encoded by fnbA/B, are major pathogenesis determinants in these infections through their involvement in S. aureus adhesion to and invasion of host cells. Sub-minimum inhibitory concentrations (sub-MICs) of antibiotics, frequently occurring in vivo because of impaired drug diffusion at the infection site, can alter S. aureus phenotype. We therefore investigated their impact on S. aureus fibronectin-mediated adhesiveness and invasiveness.MethodsAfter in vitro challenge of S. aureus 8325-4 and clinical isolates with sub-MICs of major anti-staphylococcal agents, we explored fnbA/B transcription levels, bacterial adhesiveness to immobilised human fibronectin and human osteoblasts in culture, and bacterial invasion of human osteoblasts.ResultsOxacillin, moxifloxacin and linezolid led to the development of a hyper-adhesive phenotype in the fibronectin adhesion assay that was consistent with an increase in fnbA/B transcription. Conversely, rifampin treatment decreased fibronectin binding in all strains tested without affecting fnbA/B transcription. Gentamicin and vancomycin had no impact on fibronectin binding or fnbA/B transcription levels. Only oxacillin-treated S. aureus displayed a significantly increased adhesion to cultured osteoblasts, but its invasiveness did not differ from that of untreated controls.ConclusionOur findings demonstrate that several antibiotics at sub-MICs modulate fibronectin binding in S. aureus in a drug-specific fashion. However, hyper- and hypo- adhesive phenotypes observed in controlled in vitro conditions were not fully confirmed in whole cell infection assays. The relevance of adhesion modulation during in vivo infections is thus still uncertain and requires further investigations.

【 授权许可】

Unknown   
© Rasigade et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.